The deoxyribonucleic acid (DNA) molecule is the genetic blueprint for each cell and ultimately the blueprint that determines every characteristic of a living organism. In 1953 American biochemist James Watson, left, and British biophysicist Francis Crick, right, described the structure of the DNA molecule as a double helix, somewhat like a spiral staircase with many individual steps. Their work was aided by X-ray diffraction pictures of the DNA molecule taken by British biophysicist Maurice Wilkins and British physical chemist Rosalind Franklin. In 1962 Crick, Watson, and Wilkins received the Nobel Prize for their pioneering work on the structure of the DNA molecule.
While some scientists were studying the functions of cells, others were examining details of their structure. They were aided by a crucial technological development in the 1940s, the invention of the electron microscope, which uses high-energy electrons instead of light waves to view specimens. New generations of electron microscopes have provided resolution, or the differentiation of separate objects, thousands of times more powerful than that available in light microscopes. This powerful resolution revealed organelles such as the endoplasmic reticulum, lysosomes, the Golgi apparatus, and the cytoskeleton. The scientific fields of cell structure and function continue to complement each other as scientists explore the enormous complexity of cells.
The discovery of the structure of DNA in 1953 by American biochemist James D. Watson and British biophysicist Francis Crick ushered in the era of molecular biology. Today, investigation inside the world of cells - of genes and proteins at the molecular level - constitutes one of the largest and fastest moving areas in all of science. One particularly active field in recent years has been the investigation of cell signaling, the process by which molecular messages find their way into the cell via a series of complex protein pathways in the cell.
Another busy area in cell biology concerns programmed cell death, or apoptosis. Millions of times per second in the human body, cells commit suicide as an essential part of the normal cycle of cellular replacement. This also seems to be a check against disease: When mutations build up within a cell, the cell will usually self-destruct. If this fails to occur, the cell may divide and give rise to mutated daughter cells, which continue to divide and spread, gradually forming a growth called a tumor. This unregulated growth by rogue cells can be benign, or harmless, or cancerous, which may threaten healthy tissue. The study of apoptosis is one avenue that scientists explore in an effort to understand how cells become cancerous.
Scientists are also discovering exciting aspects of the physical forces within cells. Cells employ a form of architecture called tensegrity, which enables them to withstand battering by a variety of mechanical stresses, such as the pressure of blood flowing around cells or the movement of organelles within the cell. Tensegrity stabilizes cells by evenly distributing mechanical stresses to the cytoskeleton and other cell components. Tensegrity also may explain how a change in the cytoskeleton, where certain enzymes are anchored, initiates biochemical reactions within the cell, and can even influence the action of genes. The mechanical rules of tensegrity may also account for the assembly of molecules into the first cells. Such new insights - made some 300 years after the tiny universe of cells was first glimpsed - show that cells continue to yield fascinating new worlds of discovery.
The Nervous System signifies of those elements within the animal organism that are concerned with the reception of stimuli, the transmission of nerve impulses, or the activation of muscle mechanisms.
The reception of stimuli is the function of special sensory cells. The conducting elements of the nervous system are cells called neurons; these may be capable of only slow and generalized activity, or they may be highly efficient and rapidly conducting units. The specific response of the neuron—the nerve impulse - and the capacity of the cell to be stimulated make this cell a receiving and transmitting unit capable of transferring information from one part of the body to another.
Each nerve cell consists of a central portion containing the nucleus, known as the cell body, and one or more structures referred to as axons and dendrites. The dendrites are rather short extensions of the cell body and are involved in the reception of stimuli. The axon, by contrast, is usually a single elongated extension, it is especially important in the transmission of nerve impulses from the region of the cell body to other cells.
Although all many-celled animals have some kind of nervous system, the complexity of its organization varies considerably among different animal types. In simple animals such as jellyfish, the nerve cells form a network capable of mediating only a relatively stereotyped response. In more complex animals, such as shellfish, insects, and spiders, the nervous system is more complicated. The cell bodies of neurons are organized in clusters called ganglia. These clusters are interconnected by the neuronal processes to form a ganglionated chain. Such chains are found in all vertebrates, in which they represent a special part of the nervous system, related especially to the regulation of the activities of the heart, the glands, and the involuntary Vertebrate animals have a bony spine and skull in which the central part of the nervous system is housed; The peripheral part extends throughout the remainder of the body. That part of the nervous system located in the skull is referred to as the brain, that found in the spine is called the spinal cord. The brain and the spinal cord are continuous through an opening in the base of the skull; Both are also in contact with other parts of the body through the nerves. The distinction made between the central nervous system and the peripheral nervous system is based on the different locations of the two intimately related parts of a single system. Some of the processes of the cell bodies conduct sense impressions and others conduct muscle responses, called reflexes, such as those caused by pain.
In the skin are cells of several types called receptors; each is especially sensitive to particular stimuli. Free nerve endings are sensitive to pain and are directly activated. The neurons so activated send impulses into the central nervous system and have junctions with other cells that have axons extending back into the periphery. Impulses are carried from processes of these cells to motor endings within the muscles. These neuromuscular endings excite the muscles, resulting in muscular contraction and appropriate movement. The pathway taken by the nerve impulse in mediating this simple response is in the form of a two-neuron arc that begins and ends in the periphery. Many of the actions of the nervous system can be explained on the basis of such reflex arcs, which are chains of interconnected nerve cells, stimulated at one end and capable of bringing about movement or glandular secretion at the other.
The cranial nerves connect to the brain by passing through openings in the skull, or cranium. Nerves associated with the spinal cord pass through openings in the vertebral column and are called spinal nerves. Both cranial and spinal nerves consist of large numbers of processes that convey impulses to the central nervous system and also carry messages outward; the former processes are called afferent, the latter are called efferent. Afferent impulses are referred to as sensory; efferent impulses are referred to as either somatic or visceral motor, according to what part of the body they reach. Most nerves are mixed nerves made up of both sensory and motor elements.
The cranial and spinal nerves are paired; The number in humans are 12 and 31, respectively. Cranial nerves are distributed to the head and neck regions of the body, with one conspicuous exception: the tenth cranial nerve, called the vagus. In addition to supplying structures in the neck, the vagus is distributed to structures located in the chest and abdomen. Vision, auditory and vestibular sensation, and taste is mediated by the second, eighth, and seventh cranial nerves, respectively. Cranial nerves also mediate motor functions of the head, the eyes, the face, the tongue, and the larynx, as well as the muscles that function in chewing and swallowing. Spinal nerves, after they exit from the vertebrae, are distributed in a band-like fashion to regions of the trunk and to the limbs. They interconnect extensively, thereby forming the brachial plexus, which runs to the upper extremities, and the lumbar plexus, which passes to the lower limbs.
Among the motor fibers may be found groups that carry impulses to viscera. These fibers are designated by the special name of autonomic nervous system. That system consists of two divisions, more or less antagonistic in function, that emerge from the central nervous system at different points of origin. One division, the sympathetic, arises from the middle portion of the spinal cord, joins the sympathetic ganglionated chain, courses through the spinal nerves, and is widely distributed throughout the body. The other division, the parasympathetic, arises both above and below the sympathetic, that is, from the brain and from the lower part of the spinal cord. These two divisions control the functions of the respiratory, circulatory, digestive, and urogenital systems.
Consideration of disorders of the nervous system is the province of neurology; Psychiatry deals with behavioral disturbances of a functional nature. The division between these two medical specialties cannot be sharply defined, because neurological disorders often manifest both organic and mental symptoms.
Diseases of the nervous system include genetic malformations, poisonings, metabolic defects, vascular disorders, inflammations, degeneration, and tumors, and they involve either nerve cells or their supporting elements. Vascular disorders, such as cerebral hemorrhage or other forms of a stroke, are among the most common causes of paralysis and other neurologic complications. Some diseases exhibit peculiar geographic and age distribution. In temperate zones, multiple sclerosis is a common degenerative disease of the nervous system, but it is rare in the Tropics.
The nervous system is subject to infection by a great variety of bacteria, parasites, and viruses. For example, meningitis, or infection of the meninges investing the brain and spinal cord, can be caused by many different agents. On the other hand, one specific virus causes rabies. Some viruses causing neurological ills affect only certain parts of the nervous system. For example, the virus causing poliomyelitis commonly affects the spinal cord, as Viruses manufacturing encephalitis attack the brain.
Inflammations of the nervous system are named according to the part affected. Myelitis is an inflammation of the spinal cord; Neuritis is an inflammation of a nerve. It may be caused not only by infection but also by poisoning, alcoholism, or injury. Tumors originating in the nervous system usually are composed of meningeal tissue or neuroglia (supporting tissue) cells, depending on the specific part of the nervous system affected, but other types of a tumor may metastasize to or invade the nervous system. In certain disorders of the nervous system, such as neuralgia, migraine, and epilepsy, no evidence may exist of organic damage. Another disorder, cerebral palsy, is associated with birth defects.
Pain, an unpleasant sensory and emotional experience caused by real or potential injury or damage to the body or described in terms of such damage. Scientists believe that pain evolved in the animal kingdom as a valuable three-part warning system. First, it warns of injury. Second, pain protects against further injury by causing a reflexive withdrawal from the source of injury. Finally, pain leads to a period of reduced activity, enabling injuries to heal more efficiently.
Pain is difficult to measure in humans because it has an emotional, or psychological component as well as a physical component. Some people express extreme discomfort from relatively small injuries, while others show little or no pain even after suffering severe injury. Sometimes pain is present even though no injury is apparent at all, or pain lingers long after an injury appears to have healed.
The signals that warn the body of tissue damage are transmitted through the nervous system. In this system, the basic unit is the nerve cell or neuron. A nerve cell is composed of three parts: a central cell body, a single major branching fiber called an axon, and a series of smaller branching fibers known as dendrites. Each nerve cell meets other nerve cells at certain points on the axons and dendrites, forming a dense network of interconnected nerve fibers that transmit sensory information about touch, pressure, or warmth, as well as pain.
Sensory information is transmitted from the different parts of the body to the brain via the spinal cord, which is a complex set of nerves that extend from the brain down along the back, protected by the bones of the spine. About as wide as a finger, the spinal cord is like a cable packed with many bundles of wires. The bundles are nerve pathways for transmitting information. But the spinal cord is more than just a message transmitter, it is also an extension of the brain. It contains neurons that process incoming sensory information, and generates messages to be sent back down to cells in other parts of the body.
In the nervous system, a message-carrying impulse travels from one end of a nerve cell to the other by means of an electrical impulse. When it reaches the terminal end of a nerve cell, the impulse triggers tiny sacs called presynaptic vessicles to release their contents, chemical messengers called neurotransmitters. The neurotransmitters float across the synapse, or gap between adjacent nerve cells. When they reach the neighboring nerve cell, the neurotransmitters fit into specialized receptor sites much as a key fits into a lock, causing that nerve cell to "fire," or generate an electric message-carrying impulse. As the message continues through the nervous system, the presynaptic cell absorbs the excess neurotransmitters, and repackages them in presynaptic versicles in a process called neurotransmitter reuptake.
Information being transmitted between and within the brain and spinal cord travels through the nervous system using both chemical and electrical mechanisms. A message-carrying impulse travels from one end of a nerve cell to another by means of an electric signal. When the electric signal reaches the terminal end of a nerve cell, a gap called a synapse prevents the electric signal from crossing to the next cell. The electric signal triggers the cell to release chemicals called neurotransmitters, which float across the synapse to the neighboring nerve cell. These neurotransmitters fit into specialized receptors found on the adjacent nerve cell, much as a key fits into a lock, generating an electric impulse in the neighboring cell. This new impulse travels to the end of the long cell, in turn triggering the release of neurotransmitters to carry the message across the next synapse. Not all neurotransmitters initiate a message in a neighboring nerve cell. Some specialize in preventing neighboring cells from generating an electrical signal, while others function as helpers, facilitating the message's journey to the brain.
While most of the sensory nerves in the skin and other body tissues have special structures covering their nerve endings, those nerves that signal injury have free nerve endings. These simple nerve endings specialize in detecting noxious stimuli - a catchall term for injury-causing stimuli such as intense heat, extreme pressure, or sharp pricks or cuts. The nerve endings that detect pain are called nociceptors, and the process of transmitting pain signals when harmful stimulation occurs is called nociception. Several million nociceptors are interlaced through the tissues and organs of the body.
When a person experiences an injury, such as a stubbed toe, specialized cells called nociceptors sense potential tissue damage (1) and send an electric signal, called an impulse, to the spinal cord via a sensory nerve (2). A specialized region of the spinal cord known as the dorsal horn (3) processes the pain signal, immediately sending another impulse back down the leg via a motor nerve (4). This causes the muscles in the leg to contract and pull the toe away from the source of injury (6). At the same time, the dorsal horn sends another impulse up the spinal cord to the brain. During this trip, the impulse travels between nerve cells. When the impulse reaches a nerve ending, (7) the nerve released chemical messengers, called neurotransmitters, which carry the message to the adjacent nerve. When the impulse reaches the brain (8), it is analyzed and processed as an unpleasant physical and emotional sensation.
An injury triggers pain signals in two types of nociceptors, one with large, insulated axons known as A-delta fibers and one with small, uninsulated axons known as C fibers. The large A-delta fibers conduct signals quickly, and the smaller C fibers transmit information slowly. The difference in the functions of these two fibers becomes obvious to a person who stubs a toe. At first the injured person is aware of a sharp, flashing pain at the point of injury. Generated by the A-delta fibers, this short-lived pain intrudes upon the thoughts and perceptions occurring in the brain. Just as this first pain subsides, a second pain begins that is vague, throbbing, and persistent. This sensation is derived from the C fibers.
Pain information from the A-delta and C fibers travels through the spinal cord to the brain. When it receives the pain message, the spinal cord generates impulses that travel back down to muscles, which lead to a reflexive contraction that pulls the body away from the source of injury. Other reflexes may affect skin temperature, blood flow, sweating, and other changes.
While this reflex action is underway, the pain message continues up the spinal cord to relay centers in the brain. The sensory information is routed to many other parts of the brain, including the cortex, where thinking processes occur
The Adrenal Gland is the vital endocrine gland that secretes hormones into the bloodstream, situated, in humans, on top of the upper end of each kidney. The two parts of the gland - the inner portion, or medulla, and the outer portion, or the cortex - are like separate organs: They are composed of different types of tissue and perform different functions. The adrenal medulla, composed of chromaffin cells secretes the hormone epinephrine, also called adrenaline, in response to stimulation of the sympathetic nervous system at times of stress. The medulla also secretes the hormone norepinephrine, which plays a role in maintaining normal blood circulation. The hormones of the medulla are called catecholamines. Unlike the adrenal cortex, the medulla can be removed without endangering the life of an individual.
The adrenal outer layer, or cortex, secretes about 30 steroid hormones, but only a few are secreted in significant amounts. Aldosterone, one of the most important hormones, regulates the balance of salt and water in the body. Cortisone and hydrocortisone are necessary to regulate fat, carbohydrate, and protein metabolism. Adrenal sex steroids have a minor influence on the reproductive system. Modified steroids, now produced synthetically, are superior to naturally secreted steroids for treatment of Addison's disease and other disorders.
Adrenocorticotropic Hormone is also known as corticotropin, hormones secreted by the anterior part of the pituitary gland. The specific function of ACTH is to stimulate the growth and secretions of the cortex (outer layers) of the adrenal gland. One of these secretions is cortisone, a hormone involved in carbohydrate and protein metabolisms. ACTH is used medically for its anti-inflammatory action to alleviate symptoms of allergies and arthritis. ACTH is a complex protein molecule containing 39 amino acids. Its molecular weight is approximately 5000. The biological activity of the ACTH of various animal species is similar to that of humans, but the sequence of amino acids has been found to vary somewhat among species. ACTH production is controlled in part by the hypothalamus and in part by the existing levels of adrenal gland hormones. ACTH levels increased in response to stress, disease, and decreased blood pressure.
The Pituitary Gland is the master endocrine gland in vertebrate animals. The hormones secreted by the pituitary stimulate and control the functioning of almost all the other endocrine glands in the body. Pituitary hormones also promote growth and control the water balance of the body.
The pituitary is a small bean-shaped, reddish-gray organ located in the saddle-shaped depression (sella turcica) in the floor of the skull (the sphenoid bone) and attached to the base of the brain by a stalk; it is located near the hypothalamus. The pituitary has two lobes - the anterior lobe, or adenohypophysis, and the posterior lobe, or neurohypophysis - which differ in structure and function. The anterior lobe is derived embryologically from the roof of the pharynx and is composed of groups of epithelial cells separated by blood channels; the posterior lobe is derived from the base of the brain and is composed of nervous connective tissue and nerve-like secreting cells. The area between the anterior and posterior lobes of the pituitary is called the intermediate lobe; it has the same embryological origin as the anterior lobe.
Concentrated chemical substances, or hormones, which control 10 to 12 functions in the body, have been obtained as extracts from the anterior pituitary glands of cattle, sheep, and swine. Eight hormones have been isolated, purified, and identified; All of them are peptides, that is, they are composed of amino acids. A growth hormone (GH), or the somatotropic hormone (STH), is essential for normal skeletal growth and is neutralized during adolescence by the gonadal sex hormones. Thyroid-stimulating hormones (TSH) control the normal functioning of the thyroid gland, and the adrenocorticotropic hormone (ACTH) controls the activity of the cortex of the adrenal glands and takes part in the stress reaction. Prolactin, also called lactogenic, luteotropic, or mammotropic hormone, initiates milk secretion in the mammary gland after the mammary tissues have been prepared during pregnancy by the secretion of other pituitary and sex hormones. The two gonadotropic hormones are follicle-stimulating hormones (FSH) and a luteinizing hormone (LH). Follicle-stimulating hormones stimulates the formation of the Graafian follicle in the female ovary and the development of spermatozoa in the male. The luteinizing hormone stimulates the formation of ovarian hormones after ovulation and initiates lactation in the female, in the male, it stimulates the tissues of the testes to elaborate testosterone. In 1975 scientists identified the pituitary peptide endorphin, which acts in experimental animals as a natural pain reliever in times of stress. Endorphin and ACTH are made as parts of a single large protein, which subsequently splits. This may be the body's mechanism for coordinating the physiological activities of two stress-induced hormones. The same large prohormone that contains ACTH and endorphin also contains short peptides called melanocyte-stimulating hormones. These substances are analogous to the hormone that regulates pigmentation in fish and amphibians, but in humans they have no known function.
Research has shown that the hormonal activity of the anterior lobe is controlled by chemical messengers sent from the hypothalamus through tiny blood vessels to the anterior lobe. In the 1950s, the British neurologist Geoffrey Harris discovered that cutting the blood supply from the hypothalamus to the pituitary impaired the function of the pituitary. In 1964, chemical agents called releasing factors were found in the hypothalamus; These substances, it was learned, affect the secretion of growth hormone, a thyroid-stimulating hormone called thyrotropin, and the gonadotropic hormones involving the testes and ovaries. In 1969 the American endocrinologist Roger Guillemin and colleagues isolated and characterized thyrotropin-releasing factors, which stimulates the secretion of thyroid-stimulating hormone from the pituitary. In the next few years his group and that of the American physiologist Andrew Victor Schally isolated the luteinizing hormone-releasing factor, which stimulates secretion of both LH and FSH, and somatostatin, which inhibits release of growth hormone. For this work, which proved that the brain and the endocrine system are linked, they shared the Nobel Prize in physiology or medicine in 1977. Human somatostatin was one of the first substances to be grown in bacteria by recombinant DNA.
The presence of the releasing factors in the hypothalamus helped to explain the action of the female sex hormones, estrogen and progesterone, and their synthetic versions contained in oral contraceptives, or birth-control pills. During a woman's normal monthly cycle, several hormonal changes are needed for the ovary to produce an egg cell for possible fertilization. When the estrogen level in the body declines, the follicle-releasing factor (FRF) flows to the pituitary and stimulates the secretion of the follicle-stimulating hormone. Through a similar feedback principle, the declining level of progesterone causes a release of luteal-releasing factors (LRF), which stimulates secretion of the luteinizing hormone. The ripening follicle in the ovary then produces estrogen, and the high level of that hormone influences the hypothalamus to shut down temporarily the production of FSH. Increased progesterone feedback to the hypothalamus shuts down LH production by the pituitary. The daily doses of synthetic estrogen and progesterone in oral contraceptives, or injections of the actual hormones, inhibit the normal reproductive activity of the ovaries by mimicking the effect of these hormones on the hypothalamus.
In lower vertebrates this part of the pituitary secretes melanocyte-stimulating hormones, which brings about skin-color changes. In humans, it is present only for a short time early in life and during pregnancy, and is not known to have any function.
Two hormones are secreted by the posterior lobe. One of these is the antidiuretic hormone (ADH), vasopressin. Vasopressin stimulates the kidney tubules to absorb water from the filtered plasma that passes through the kidneys and thus controls the amount of urine secreted by the kidneys. The other posterior pituitary hormone is oxytocin, which causes the contraction of the smooth muscles in the uterus, intestines, and blood arterioles. Oxytocin stimulates the contractions of the uterine muscles during the final stage of pregnancy to stimulate the expulsion of the fetus, and it also stimulates the ejection, or let-down, of milk from the mammary gland following pregnancy. Synthesized in 1953, oxytocin was the first pituitary hormone to be produced artificially. Vasopressin was synthesized in 1956.
Pituitary functioning may be disturbed by such conditions as tumors, blood poisoning, blood clots, and certain infectious diseases. Conditions resulting from a decrease in anterior-lobe secretion include dwarfism, acromicria, Simmonds's disease, and Fröhlich's syndrome. The dwarfism occurs when anterior pituitary deficiencies occur during childhood; acromicria, in which the bones of the extremities are small and delicate, results when the deficiency occurs after puberty. Simmonds's disease, which is caused by extensive damage to the anterior pituitary, is characterized by premature aging, loss of hair and teeth, anemia, and emaciation; it can be fatal. Fröhlich's syndrome, also called adiposogenital dystrophy, is caused by both anterior pituitary deficiency and a lesion of the posterior lobe or hypothalamus. The result is obesity, dwarfism, and retarded sexual development. Glands under the influence of anterior pituitary hormones are also affected by anterior pituitary deficiency.
Over secretion of one of the anterior pituitary hormones, somatotropin, results in a progressive chronic disease called acromegaly, which is characterized by enlargement of some parts of the body. Posterior-lobe deficiency results in diabetes insipidus.
Tissue - a group of associated, similarly structured cells that perform specialized functions for the survival of the organism. Animal tissues, to which this article is limited, take their first form when the blastula cells, arising from the fertilized ovum, differentiate into three germ layers: the ectoderm, mesoderm, and endoderm. Through further cell differentiation, or histogenesis, groups of cells grow into more specialized units to form organs made up, usually, of several tissues of similarly performing cells. Animal tissues are classified into four main groups.
These tissues include the skin and the inner surfaces of the body, such as those of the lungs, stomach, intestines, and blood vessels. Because its primary function is to protect the body from injury and infection, epitheliums are made up of tightly packed cells with little intercellular substance between them.
About 12 kinds of epithelial tissue occur. One kind is stratified squamous tissue found in the skin and the linings of the esophagus and vagina. It is made up of thin layers of flat, scalelike cells that form rapidly above the blood capillaries and is pushed toward the tissue surface, where they die and are shed. Another is a simple columnar epithelium, which lines the digestive system from the stomach to the anus; Simple columnar epithelium cells stand upright and not only control the absorption of nutrients but also secrete mucus through individual goblet cells. Glands are formed by the inward growth of epithelium-for examples, the sweat glands of the skin and the gastric glands of the stomach. Outward growth results in hair, nails, and other structures.
These tissues, which support and hold parts of the body together, comprises the fibrous and elastic connective tissues, the adipose (fatty) tissues, and cartilage and bone. In contrast to an epithelium, the cells of these tissues are widely separated from one another, with a large amount of intercellular substance between them. The cells of fibrous tissue, found throughout the body, connect to one another by an irregular network of strands, forming a soft, cushiony layer that also supports blood vessels, nerves, and other organs. Adipose tissue has a similar function, except that its fibroblasts also contain store fat. Elastic tissue, found in ligaments, the trachea, and the arterial walls, stretches and contracts again with each pulse beat. In the human embryo, the fibroblast cells that originally secreted collagen for the formation of fibrous tissue later change to secrete a different form of protein called chondrion, for the formation of cartilage, some cartilage later becomes calcified by the action of osteoblast to form bones. Blood and lymph are also often considered connective tissues.
Tissues, which contract and relax, comprise the striated, smooth, and cardiac muscles. Striated muscles, also called skeletal or voluntary muscles, include those that are activated by the somatic, or voluntary, nervous system. They are joined together without cell walls and have several nuclei. The smooth, or involuntary muscles, which are activated by the autonomic nervous system, are found in the internal organs and consist of simple sheets of cells. Cardiac muscles, which have characteristics of both striated and smooth muscles, are joined together in a vast network. These highly complex groups of cells, called ganglia, transfer information from one part of the body to another. Each neuron, or nerve cell, consists of a cell body with branching dendrites and one long fiber, or axons. The dendrites connect one neuron to another; The axon transmits impulses to an organ or collects impulses from a sensory organ.
Once, again, in the nervous system, a message-carrying impulse travels from one end of a nerve cell to the other by means of an electrical impulse. When it reaches the terminal end of a nerve cell, the impulse trigger’s tiny sacs called presynaptic vessicles to release their contents, chemical messengers called neurotransmitters. The neurotransmitters float across the synapse, or gap between adjacent nerve cells. When they reach the neighboring nerve cell, the neurotransmitters fit into specialized receptor sites much as a key fits into a lock, causing that nerve cell to fire or generate an electric message-carrying impulse. As the message continues through the nervous system, the presynaptic cell absorbs the excess neurotransmitters, and repackages them in presynaptic versicles in a process called neurotransmitter reuptake.
Reflex, in physiology, is the involuntary response to a stimulus by the animal organism. In its simplest form, it consisted of the stimulation of an afferent nerve through a sense organ, or receptor, followed by transmission of the stimulus, usually through a nerve center, to an efferent motor nerve, resulting in action of a muscle or gland, called the effector. In most reflex action, however, the stimulus passes through one or more intermediate nerve cells, which modify and direct its action, sometimes to the extent of involving the muscular activity of the entire organism. For example, a painful stimulus applied to the hand causes a reflex withdrawal of the hand, which involves contraction of the flexor group of muscles and reflexation of the opposing extensor group; if the stimulus is strong, the coordinating nerve cells pass it to the arm muscles and also to the muscles of the trunk and legs, the result being a jump that removes not only the arm, but the entire person from the vicinity of the painful stimulus.
The system of coordinating nerve cells is such that several different kinds of stimuli may produce the same result. For example, the stimulus produced by the sight of food and that caused by the smell of food travel different afferent pathways, but both have a common final path that stimulates the salivary glands to secretion. The final common path may also be activated through associated nerve tracts by a stimulus that ordinarily is not directly connected with the response. This type of reflex was named conditioned reflex by its discoverer, the Russian physiologist Ivan Pavlov, about 1904. Pavlov found that sounding a bell every time a dog was about to be given food eventually caused a reflex flow of saliva, which later persisted even when no food was produced. Elaborations of this habituative type of reflex are regarded by some physiologists and psychologists as an important basis for many behaviors, both voluntary and involuntary.
The normal pathways of many reflexes are generally known, and the presence, absence, or exaggerations of the normal physical responses to certain stimuli are symptoms used by neurologists to determine the condition of the neural pathways involved. A familiar reflex commonly tested by physicians is the patellar reflex, in which an involuntary jerk of the knee is evoked by lightly striking the tendon of the patella, or kneecap, indicating the efficiency of certain nerve tracts in the spinal cord.
Like all other cells, neurons contain charged ions: Potassium and sodium (positively charged) and chlorine (negatively charged). Neurons differ from other cells in that they are able to produce a nerve impulse. A neuron is polarized - that is, it has an overall negative charge inside the cell membrane because of the high concentration of chlorine ions and low concentration of potassium and sodium ions. The concentration of these same ions is exactly reversed outside the cell. This charge differential represents stored electrical energy, sometimes referred to as membrane potential or resting potential. The negative charge inside the cell is maintained by two features. The first is the selective permeability of the cell membrane, which is more permeable to potassium than sodium. The second feature is sodium pumps within the cell membrane that actively pump sodium out of the cell. When depolarization occurs, this charge differential across the membrane is reversed, and a nerve impulse is produced.
Depolarization is a rapid change in the permeability of the cell membrane. When sensory input or any other kind of stimulating current is received by the neuron, the membrane permeability is changed, allowing a sudden influx of sodium ions into the cell. The high concentration of sodium, or action potential, changes the overall charge within the cell from negative to positive. The local changes in ion concentration triggers similar reactions along the membrane, propagating the nerve impulse. After a brief period called the refractory period, during which the ionic concentration returned to resting potential, the neuron can repeat this process.
Nerve impulses travel at different speeds, depending on the cellular composition of a neuron. Where speed of impulse is important, as in the nervous system, axons are insulated with a membranous substance called myelin. The insulation provided by myelin maintains the ionic charge over long distances. Nerve impulses are propagated at specific points along the myelin sheath; These points are called the nodes of Ranvier. Examples of myelinated axons are those in sensory nerve fibers and nerves connected to skeletal muscles. In non-myelinated cells, the nerve impulse is propagated more diffusely.
The nervous system has two divisions: The somatic, which allow voluntary control over skeletal muscle, and the autonomic, which is involuntary and controls cardiac and smooth muscle and glands. The autonomic nervous system has two divisions: The sympathetic and the parasympathetic. Many, but not all, of the muscles and glands that distribute nerve impulses to the larger interior organs possess a double nerve supply; in such cases the two divisions may exert opposing effects. Thus, the sympathetic system increases heartbeat, and the parasympathetic system decreases heartbeat. The two nervous systems are not always antagonistic, however. For example, both nerve supplies to the salivary glands excite the cells of secretion. Furthermore, a single division of the autonomic nervous system may both excite and inhibit a single effector, as in the sympathetic supply to the blood vessels of skeletal muscle. Finally, the sweat glands, the muscles that cause involuntary erection or bristling of the hair, the smooth muscle of the spleen, and the blood vessels of the skin and skeletal muscle are actuated only by the sympathetic division.
Voluntary movement of head, limbs, and body is caused by nerve impulses arising in the motor area of the cortex of the brain and carried by cranial nerves or by nerves that emerge from the spinal cord to connect with skeletal muscles. The reaction involves both excitation of nerve cells stimulating the muscles involved and inhibition of the cells that stimulate opposing muscles. A nerve impulse is an electrical change within a nerve cell or fiber; Measured in millivolts, it lasts a few milliseconds and can be recorded by electrodes.
The human brain has three major structural components: The large dome-shaped cerebrum, the smaller somewhat spherical cerebellum, and the brainstem. Prominent in the brainstem are the medulla oblongata (the egg-shaped enlargement at the center) and the thalamus (between the medulla and the cerebrum). The cerebrum is responsible for intelligence and reasoning. The cerebellum helps to maintain balance and posture. The medulla is involved in maintaining involuntary functions such as respiration, and the thalamus acts as a relay center for electrical impulses traveling to and from the cerebral cortex. Lack of blood flow to any part of the brain results in a stroke, permanent damage that interferes with the functions of the affected part of the brain.
Movement may occur also in direct response to an outside stimulus, thus, a tap on the knee causes a jerk, and a light shone into the eye makes the pupil contract. These involuntary responses are called reflexes. Various nerve terminals called receptors constantly send impulses into the central nervous system. These are of three classes: exteroceptors, which are sensitive to pain, temperature, touch, and pressure; interoceptors, which react to changes in the internal environment; and proprioceptors, which respond to variations in movement, position, and tension. These impulses terminate in special areas of the brain, as do of those special receptors concerned with sight, hearing, smell, and taste.
Whereas most major nerves emerge from the spinal cord, the 12 pairs of cranial nerves project directly from the brain. All but 1 pair relay motor or sensory information (or both); the tenth, or vagus nerve, affects visceral functions such as heart rate, vasoconstriction, and contraction of the smooth muscle found in the walls of the trachea, stomach, and intestine.
Muscular contractions do not always cause actual movement. A small fraction of the total number of fibers in most muscles are usually contracting. This serves to maintain the posture of a limb and enables the limb to resist passive elongation or stretch. This slight continuous contraction is called muscle tone.
In 1946 Axelrod joined the laboratory of American pharmacologist Bernard Brodie at Goldwater Memorial Hospital in New York. The pair conducted research on pain-relieving drugs called analgesics. They identified a pain-relieving chemical known as acetaminophen. This drug was later developed and marketed by the drug company Johnson & Johnson under the brand-name Tylenol.
In 1949 Axelrod took a position at the National Heart Institute, a branch of the National Institutes of Health (NIH). There Axelrod studied how the body processes certain drugs that cause behavioral changes, including amphetamines, ephedrine, and mescaline. He identified a group of enzymes that help these drugs break down in the body. These enzymes, called cytochrome-P450 monoxygenases, have been studied extensively by other scientists, particularly in cancer research.
Realizing that career advancement in the sciences requires a doctoral degree, in 1954 Axelrod took a leave of absence from his job at the National Heart Institute to attend The George Washington University. He earned his doctorate in pharmacology in 1955. That same year he was named chief of pharmacology at the National Institute of Mental Health (NIMH) another branch of NIH.
At NIMH, Joseph Axelrod began research on neurotransmitters. A nerve cell releases a neurotransmitter to spur a neighboring cell into action. In the 1950s most scientists believed that a neurotransmitter became inactive once it stimulated a neighboring cell. But Axelrod’s research found that the neurotransmitter returns to the first nerve cell, in a process known as reuptake, where it is broken down by enzymes or repackaged for reuse. This research led to the creation of a number of drugs that prevent the reuptake process, enabling a neurotransmitter to remain active for a longer period of time.
Axelrod’s research revolutionized the understanding of many mental-health disorders, including depression, anxiety, and schizophrenia. Prior to his research, psychiatry focused on the relationship of life experiences to mental health problems. But Axelrod's research proved that mental-health disorders were often the result of complicated brain chemistry. His research spurred the development of new drugs that advanced the treatment of mental-health conditions. Among these are selective serotonin reuptake inhibitors, including the antidepressants fluoxetine, sold under the brand name Prozac, sertraline (Zoloft) and paroxetine (Paxil).
The study of the biochemistry of memory is another exciting scientific enterprise, but one that can only be touched upon here. Scientists estimate that an adult human brain contains about 100 billion neurons. Each of these is connected to hundreds or thousands of other neurons, forming trillions of neural connections. Neurons communicate by chemical messengers called neurotransmitters. An electrical signal travels along the neuron, triggering the release of neurotransmitters at the synapse, the small gap between neurons. The neurotransmitters travel across the synapse and act on the next neuron by binding with protein molecules called receptors. Most scientists believe that memories are somehow stored among the brain's trillions of synapses, rather than in the neurons themselves.
Scientists who study the biochemistry of learning and memory often focus on the marine snail Aplysia because its simple nervous system allows them to study the effects of various stimuli on specific synapses. A change in the snail's behavior due to learning can be correlated with a change at the level of the synapse. One exciting scientific frontier is discovering the changes in neurotransmitters that occur at the level of the synapse.
Other researchers have implicated glucose, a sugar and insulin(a hormone secreted by the pancreas) as important to learning and memory. Humans and other animals given these substances show an improved capacity to learn and remember. Typically, when animals or humans ingest glucose, the pancreas responds by increasing insulin production, so it is difficult to determine which substance contributes to improved performance. Some studies in humans that have systematically varied the amount of glucose and insulin in the blood have shown that insulin may be the more important of the two substances for learning.
Scientists also have examined the influence of genes on learning and memory. In one study, scientists bred strains of mice with extra copies of a gene that helps build a protein called N-methyl-D-aspartate, or NMDA. This protein acts as a receptor for certain neurotransmitters. The genetically altered mice outperformed normal mice on a variety of tests of learning and memory. In addition, other studies have found that chemically blocking NMDA receptor impairs learning in laboratory rats. Future discoveries from genetic and biochemical studies may lead to treatments for memory deficits from Alzheimer's disease and other conditions that affect memory.
Alzheimer's Disease, progressive brain disorders that causes a gradual and irreversible decline in memory, language skills, perception of time and space, and, eventually, the ability to care for oneself. First described by German psychiatrist Alois Alzheimer in 1906, Alzheimer's disease was initially thought to be a rare condition affecting only young people, and was referred to as prehensile dementia. Today late-onset Alzheimer's disease is recognized as the most common cause of the loss of mental function in those aged 65 and over. Alzheimer's in people in their 30s, 40s, and 50s, called early-onset Alzheimer's disease, occurs less frequently, accountings for less than 10 percent of the estimated 4 million Alzheimer's cases in the United States.
Although Alzheimer's disease is not a normal part of the aging process, the risk of developing the disease increases as people grow older. About 10 percent of the United States population over the age of 65 is affected by Alzheimer's disease, and nearly 50 percent of those over age 85 may have the disease.
Alzheimer's disease takes a devastating toll, not only on the patients, but also on those who love and care for them. Some patients experience immense fear and frustration as they struggle with once commonplace tasks and slowly lose their independence. Family, friends, and especially those who provide daily care suffer immeasurable pain and stress as they witness Alzheimer's disease slowly take their loved one from them.
The onset of Alzheimer's disease is usually very gradual. In the early stages, Alzheimer's patients have relatively mild problems learning new information and remembering where they have left common objects, such as keys or a wallet. In time, they begin to have trouble recollecting recent events and finding the right words to express themselves. As the disease progresses, patients may have difficulty remembering what day or month it is, or finding their way around familiar surroundings. They may develop a tendency to wander off and then be unable to find their way back. Patients often become irritable or withdrawn as they struggle with fear and frustration when once commonplace tasks become unfamiliar and intimidating. Behavioral changes may become more pronounced as patients become paranoid or delusional and unable to engage in normal conversation.
Eventually Alzheimer's patients become completely incapacitated and unable to take care of their most basic life functions, such as eating and using the bathroom. Alzheimer's patients may live many years with the disease, usually dying from other disorders that may develop, such as pneumonia. Typically the time from initial diagnosis until death is seven to ten years, but this is quite variable and can range from three to twenty years, depending on the age of the onset, other medical conditions present, and the care patients receive.
The brains of patients with Alzheimer's have distinctive formations - abnormally shaped proteins called tangles and plaques - that are recognized as the hallmark of the disease. Not all brain regions show these characteristic formations. The areas most prominently affected are those related to memory.
Tangles are long, slender tendrils found inside nerve cells, or neurons. Scientists have learned that when a protein-called tau becomes altered, it may cause the characteristic tangles in the brain of the Alzheimer’s patient. In healthy brains, tau provides structural support for neurons, but in Alzheimer's patients this structural support collapses.
Plaques, or clumps of fibers, form outside the neurons in the adjacent brain tissue. Scientists found that a type of protein, called amyloid precursor protein, forms toxic plaques when it is cut in two places. Researchers have isolated the enzyme beta-secretes, which is believed to make one of the cuts in the amyloid precursor protein. Researchers also identified another enzyme, called gamma secretes, that makes the second cut in the amyloid precursor protein. These two enzymes snip the amyloid precursor protein into fragments that then accumulate to form plaques that are toxic to neurons.
Scientists have found that tangles and plaques cause neurons in the brains of Alzheimer's patients to shrink and eventually die, first in the memory and language centers and finally throughout the brain. This widespread neuron degeneration leaves gaps in the brain's messaging network that may interfere with communication between cells, causing some of the symptoms of Alzheimer’s disease.
Alzheimer's patients have lower levels of neurotransmitters, chemicals that carry complex messages back and forth between the nerve cells. For instance, Alzheimer's disease seems to decrease the level of the neurotransmitter acetylcholine, which is known to influence memory. A deficiency in other neurotransmitters, including somatostatin and corticotropin-releasing factor, and, particularly in younger patients, serotonin and norepinephrine, also interferes with normal communication between brain cells.
The causes of Alzheimer's disease remain a mystery, but researchers have found that particular groups of people have risk factors that make them more likely to develop the disease than the general population. For example, people with a family history of Alzheimer's are more likely to develop Alzheimer's disease.
Some of the most promising Alzheimer's research is being conducted in the field of genetics to learn the role a family history of the disease has in its development. Scientists have learned that people who are carriers of a specific version of the apolipoprotein E gene (apoE genes), found on chromosome 19, are several times more likely to develop Alzheimer's than carriers of other versions of the apoE gene. The most common version of this gene in the general population is apoE3. Nearly half of all late-onset Alzheimer’s patients have the fewer in common apoE4 versions, however, and research has shown that this gene plays a role in Alzheimer's disease. Scientists have also found evidence that variations in one or more genes located on chromosomes 1, 10, and 14 may increase a person’s risk for Alzheimer's disease. Scientists have identified the gene variations on chromosomes 1 and 14 and learned that these genes produce mutations in proteins called presenilins. These mutated proteins apparently trigger the activity of the enzyme gamma secretase, which splices the amyloid precursor protein.
Researchers have made similar strides in the investigation of early-onset Alzheimer's disease. A series of genetic mutations in patients with early-onset Alzheimer's has been linked to the production of amyloid precursor protein, the protein in plaques that may be implicated in the destruction of neurons. One mutation is particularly interesting to geneticists because it occurs on a gene involved in the genetic disorder Down syndrome. People with Down syndrome usually develop plaques and tangles in their brains as they get older, and researchers believe that learning more about the similarities between Down syndrome and Alzheimer's may further our understanding of the genetic elements of the disease.
Some studies suggest that one or more factors other than heredity may determine whether people develop the disease. One study published in February 2001 compared residents of Ibadan, Nigeria, who eat a mostly low-fat vegetarian diet, with African Americans living in Indianapolis, Indiana, whose diet included a variety of high-fat foods. The Nigerians were less likely to develop Alzheimer’s disease compared to their U.S. counterparts. Some researchers suspect that health imposes on high blood pressure, atherosclerosis (arteries clogged by fatty deposits), high cholesterol levels, or other cardiovascular problems may play a role in the development of the disease.
Other studies have suggested that environmental agents may be a possible cause of Alzheimer's disease; for example, one study suggested that high levels of aluminum in the brain may be a risk factor. Several scientists initiated research projects to further investigate this connection, but no conclusive evidence has been found linking aluminum with Alzheimer's disease. Similarly, investigations into other potential environmental causes, such as zinc exposure, viral agents, and food-borne poisons, while initially promising, have generally turned up inconclusive results.
Some studies indicate that brain trauma can trigger a degenerative process that results in Alzheimer's disease. In one study, an analysis of the medical records scribed upon veterans of World War II (1939-1945) linked serious head injury in early adulthood with Alzheimer's disease in later life. The study also looked at other factors that could possibly influence the development of the disease among the veterans, such as the presence of the apoE gene, but no other factors were identified.
Alzheimer’s disease is only positively diagnosed by examining brain tissue under a microscope to see the hallmark plaques and tangles, and this is only possible after a patient dies. As a result, physicians rely on a series of other techniques to diagnose probable Alzheimer's disease in living patients. Diagnosis begins by ruling out other problems that cause memory loss, such as stroke, depression, alcoholism, and the use of certain prescription drugs. The patient undergoes a thorough examination, including specialized brain scans, to eliminate other disorders. The patient may be given a detailed evaluation called a neuropsychological examination, which is designed to evaluate a patient’s ability to perform specific mental tasks. This helps the physician determine whether the patient is showing the characteristic symptoms of Alzheimer's disease - progressively worsening memory problems, language difficulties, and trouble with spatial direction and time. The physician also asks about the patient's family medical history to learn about any past serious illnesses, which may give a hint about the patient's current symptoms.
Evidence shows that there is inflammation in the brains of Alzheimer's patients, which may be associated with the production of amyloid precursor protein. Studies are underway to find drugs that prevent this inflammation, to possibly slow or even halt the progress of the disease. Other promising approaches center on mechanisms that manipulate amyloid precursor protein production or accumulation. Drugs are in development that may block the activity of the enzymes that cut the amyloid precursor protein, halting amyloid production. Other studies in mice suggest those vaccinating animals with amyloid precursor protein can produce a reaction that clears amyloid precursor protein from the brain. Physicians have started vaccination studies in humans to determine if the same potentially beneficial effects can be obtained. There is still much to be learned, but as scientists better understand the genetic components of Alzheimer’s, the roles of the amyloid precursor protein and the tau protein in the disease, and the mechanisms of nerve cell degeneration, the possibility that a treatment will be developed is more likely.
The responsibility for caring for Alzheimer's patients generally falls on their spouses and children. Care givers must constantly be on guard for the possibility of Alzheimer's patients wandering away or becoming agitated or confused in a manner that jeopardizes the patient or others. Coping with a loved one's decline and inability to recognize familiar face causes enormous pain.
The increased burden faced by families is intense, and the life of the Alzheimer's care giver is often called a 36-hour day. Not surprisingly, care givers often develop health and psychological problems of their own as a result of this stress. The Alzheimer's Association, a national organization with local chapters throughout the United States, was formed in 1980 in large measure to provide support for Alzheimer's care givers. Today, national and local chapters are a valuable source for information, referral, and advice.
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