two separate groups of cells compose the nervous system. Neurons are functional nerve cells; they range in size from the smallest (5 µm) to the largest (150 µm) cell of the body and are responsible for conveying information to and away from the cns.
Neuroglial cells provide physical and metabolic support for the neurons.
STRucTuRE AND fuNcTIoN of NEuRoNS
the typical neuron is composed of a cell body (peri- karyon or soma) that consists of a nucleus sur- rounded by the perinuclear cytoplasm and two types of processes, several dendrites, and a single axon (Fig. 9.2).
• Cell bodies may be of different sizes and shapes, but in the cns, most tend to be polygonal shaped, whereas cell bodies of the sensory ganglia are spherical. the cell body houses the nucleus, as well as various organelles, the most prominent of which are the rough endoplasmic reticulum (ReR) (Nissl body of light
microscopy), the large perinuclear golgi apparatus, abundant mitochondria; and a well-developed system of microtubules, microfilaments, and neurofilaments. the microtubules sport microtubule-associated protein 2 (MAP-2). the soma also houses inclusions such as lipofuscin, an age-related substance believed to be the indigestible remnants of lysosomal degradation; melanin, a dark brown pigment that may be the remnant of the synthesis of certain neurotransmitters (e.g., noradrenaline and dopamine); secretory granules, probably containing neurotransmitter substances; and lipid droplets.
• Dendrites, cell processes that receive stimuli originating from outside and inside the body, often form branches and may arborize to receive stimuli from multiple sources at the same time, which they transmit as an impulse toward the cell body. neurons usually have several dendrites, each of which possesses organelles, but not golgi, in their proximal regions. these processes are usually broader near the soma, but begin to taper at a distance. the neurofilaments of dendrites usually contact microtubules, which have MAP-2 associated proteins. As dendrites branch, they form numerous synapses and the dendrites of some neurons form small bulges, or spines, on their surface that provide larger surface areas for synapse formation.
• the cell body of a neuron possesses only a single axon that arises from a specialized region on the
cell body called the axon hillock. An axon may extend long distances to provide motor supply to muscles and glands. the axon diameter varies and is related to the conduction velocity (i.e., as axon diameter increases, conduction velocity increases). the diameter is specific for the type of neuron, however. Although there is only one axon, it may give off branches at right angles, known as collateral axons, and as it
approximates its target, it may arborize. Axons end in axon terminals (end bulbs, end-foot, terminal boutons) where they form synaptic junctions (synapses) with other cells.
• the axon hillock is a specialized region of the cell body that occupies the opposite side of the cell body from where dendrites originate.
the cytoplasm within the region of the axon hillock is devoid of ReR, golgi, ribosomes, and nissl bodies but is rich in microtubules and neurofilaments perhaps regulating axon diameter.
• on exiting the cell body, the axon’s initial segment is without myelin and is termed the spike trigger zone where excitatory and inhibitory impulses are summed and evaluated to decide whether or not the impulse is to be transmitted.
• Because the axoplasm (cytoplasm within the axon) is devoid of ReR and polyribosomes, its maintenance is provided by the cell body. the axoplasm does possess, however, smooth endoplasmic reticulum (seR), abundant elongated mitochondria, microtubules with their associated protein MAP-3, and neurofilaments at the distal end.
• Oligodendroglia in the cns and Schwann cells in the Pns form a myelin sheath (white in color) that surrounds some axons. the cns is divided into white matter, where most of the axons are myelinated, and gray matter, where most axons are not myelinated.
• Materials within the axoplasm and the cell body are ferried by a process called axonal transport, which occurs in two directions:
• Anterograde transport conveys materials such as organelles, vesicles, actin, myosin, clathrin, and enzymes required for the synthesis of neurotransmitters in the axon terminal, toward the end-foot. the axon uses the motor protein kinesin for anterograde transport.
• Retrograde transport conveys material, such as tubulin monomers and dimers, neurofilament subunits, enzymes, viruses, and molecules to be degraded, to the soma. the axon uses the motor protein dynein for retrograde transport.
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Figure 9.2 Ultrastructure of a neuron cell body. (From Gartner LP, Hiatt JL: Color Textbook of Histology, 3rd ed. Philadelphia, Saunders, 2007, p 190.)
Lipofuscin granule
Dendrite
Synapse
Synaptic vesicle
Golgi
Nissl substance Lysosomes Ribosomes
Microtubule Axon
Smooth endoplasmic reticulum
cLINIcAL coNSIDERATIoNS
Certain viruses, such as herpes simplex and the rabies virus, employ retrograde axonal transport as a means of spreading from neuron to neuron within a chain. Also, toxins, such as Clostridium tetani—which causes tetanus—are spread in the same manner from the periphery to the CNS.
Most intracranial tumors are of neuroglial origin, and only rarely result from CNS neurons.
Neuroglial tumors include benign oligodendrogliomas and fatal malignant
astrocytomas. Other intracranial tumors that arise from the connective tissues of the nervous system include benign fibroma and malignant sarcoma.
neuroblastoma, an extremely malignant tumor that attacks mainly infants and young children, is a PNS tumor located within the suprarenal gland.
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112 NEuRoN cLASSIfIcATIoN
the three categories of neurons are based on their morphology and the organization of their processes (Fig. 9.3):
• Unipolar neurons (pseudounipolar neurons) are located in the dorsal root ganglion and some ganglia of the cranial nerves. they possess only one process; however, that single process
bifurcates into a peripheral branch that continues until it reaches the site it services and a central branch that gains entry to the cns. the peripheral branch arborizes with receptor endings similar to a dendrite, and it functions as a receptor. the impulse passes to the central process, but bypasses the cell body.
• Bipolar neurons are found in the olfactory epithelium and in the ganglia of the vestibulocochlear nerve. they possess two processes—a dendrite and an axon.
• Multipolar neurons are ubiquitous, are generally motoneurons, and are located in the spinal cord and in the cerebral and cerebellar cortices. they possess several dendrites and one axon.
there are also three categories of neurons based on their function:
• Sensory (afferent) neurons are stimulated at their dendritic receptors at the periphery where they respond to external environmental stimuli, and from within the body where they respond to internal environmental stimuli and transmit the information to the cns for processing.
• Motor (efferent) neurons originate in the cns and transmit their impulses to other neurons, muscles, and glands.
• Interneurons, present solely within the cns, function as intermediaries between sensory neurons and motoneurons; they establish and integrate the activities of neuronal circuits.
NEuRoGLIAL cELLS
Neuroglial cells (Fig. 9.4) are at least 10 times more abundant than neurons, and although they cannot transmit nerve impulses, they have the essential func- tion of providing support and protection for the neurons whose soma, dendrites, and axons they envelop. in contrast to neurons, neuroglial cells can undergo cell division. neuroglial cells that function
within the cns include oligodendrocytes, microglia, astrocytes, and ependymal cells; schwann cells are neuroglia cells in the Pns.
• Oligodendrocytes are of two types:
• Interfascicular oligodendrocytes produce myelin, insulating axons of the cns. A single oligodendrocyte may wrap several axons together in myelin.
• Satellite oligodendrocytes surround the soma of large neurons and probably function to insulate them from unwanted contact.
• Microglial cells are small cells that originate in the bone marrow and serve as macrophages, belonging to the mononuclear phagocyte system.
they reside in the cns where they phagocytose debris and damaged cells and mount protection against viruses, microorganisms, and tumors.
Additionally, they serve as antigen-presenting cells and secrete cytokines.
• there are two types of astrocytes—protoplasmic astrocytes located in the gray matter of the cns and fibrous astrocytes located in the white matter. it has been proposed, however, that there is only a single type of astrocyte, and the presence of astrocytes in two different locations is responsible for their dissimilar characteristics.
Both types of astrocytes possess intermediate filaments whose unique glial fibrillar acidic protein is a distinguishing characteristic of these cells. Astrocytes scavenge accumulated products, including ions and neurotransmitters and their metabolic remnants in their immediate area.
Additional functions of astrocytes include repairing damage in the cns, where they form scar tissue composed solely of cells; releasing glucose to nourish neurons of the cerebral cortex;
and participating with the endothelial cells of blood vessels in the formation of the blood-brain barrier (BBB).
• Protoplasmic astrocytes possess pedicels (vascular feet) contacting blood vessels. others located adjacent to the pia of the brain or spinal cord possess pedicles that touch each other to form a thin layer that contact the pia mater, establishing the pia-glial membrane.
• Fibrous astrocytes possess long processes that associate with blood vessels and pia mater, but contact is prevented by their basal lamina.
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Figure 9.3 types of neurons. (From Gartner LP, Hiatt JL: Color Textbook of Histology, 3rd ed. Philadelphia, Saunders, 2007, p 189.) Cell
body
Axon Pyramidal
(hippocampus) Purkinje
(cerebellum) Axon Axon
Axon
Dendrites Dendrites
Cell body
Cell body
Bipolar
(retina) Unipolar
(pseudounipolar) Multipolar (motor)
Dendrites
Figure 9.4 types of neuroglial cells. (From Gartner LP, Hiatt JL: Color Textbook of Histology, 3rd ed. Philadelphia, Saunders, 2007, p 193.)
Blood vessel
Perivascular foot
Protoplasmic
astrocyte Fibrous
astrocyte
Microglia Oligodendrocyte
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114 NEuRoGLIAL cELLS (cont.)
• Ependymal cells are cuboidal cells that line the ventricles of the brain and the central canal of the spinal cord. they also contribute to the formation of the choroid plexus, the structure responsible for the production of the
cerebrospinal fluid (CSF). certain ependymal cells are ciliated, assisting in circulating the csF, and others, known as tanycytes, have been implicated in the transfer of csF to neurosecretory cells of the hypothalamus.
• Schwann cells arise from neural crest cells, and although they are considered neuroglial cells, they are located exclusively in the Pns (Fig. 9.5).
similar to oligodendrocytes, schwann cells form a myelinated or unmyelinated sheath around axons, insulating them; however, in contrast to oligodendroglia, a single schwann cell can myelinate only a single axon; however, several unmyelinated axons can be ensheathed by a single schwann cell. the myelin sheath is the plasmalemma of the schwann cell that is wrapped around the axon as many as 50 times.
thousands of schwann cells line up side by side, and each wraps its plasma membrane around a small length of the axon. the region of the axon wrapped by one schwann cell is known as the internodal segment. the region between two adjoining internodal segments lacks myelin and is referred to as the node of Ranvier. Because each schwann cell has its own basal lamina, the axon at the node of Ranvier is covered by interdigitations of the schwann cell processes and by the schwann cell’s basal lamina; thus, the axon is not exposed directly to its surrounding environment. oligodendroglia do not form processes at the nodes of Ranvier; instead, the region of the node is occupied by the process of an astrocyte. (Fig. 9.6).
• Although the axons of many neurons are myelinated in adults, not all axons are myelinated at the same time during development. sensory nerves are not myelinated completely until several months after birth, whereas motor axons are almost completely myelinated at birth. in the cns, the axons of some of the fiber tracts are not myelinated for the first few years of life.
• Myelination is a complex and as yet incompletely understood process. the schwann cell (or oligodendroglion in the
cns) membrane wraps around the axon, and during the wrapping process the cytoplasm is squeezed back into the cell body. the inner aspect of the plasmalemma comes very close to the inner aspect of the plasmalemma, and the outer aspect comes very close to the outer aspect, and this relationship is repeated with each turn of the wrapping.
• Viewed with the electron microscope, the spiraling membrane presents a wider, darker line—the major dense line that indicates the contact between the two cytoplasmic aspects of the schwann cell plasma membrane. the contact between the outer surfaces of the plasma membrane is noted as a thinner, intraperiod line. the major dense line and the intraperiod line alternate with one another. At very high resolution, a narrow gap is visible within the intraperiod line, known as the intraperiod gap; this is a very narrow
extracellular space that permits communication between the axon and the milieu outside the myelin sheath. naturally, only small ions are capable of traversing the intraperiod gap.
• certain regions of the myelin sheath have residual cytoplasm, and they appear as bleblike areas known as Schmidt-Lanterman incisures.
• the schwann cell membrane that forms the myelin sheath is rich in glycoproteins and sphingomyelin and two essential protein components, myelin protein zero (MPZ) and myelin basic protein (MBP). MPZ not only facilitates the process of myelin formation, but also assists in stabilizing the myelin sheath. MBP is also believed to help in maintaining the stability of the myelin sheath. MPZ is not present in myelin of the cns; instead, another protein, proteolipid protein (PLP), assumes its functions.
• the external aspects of the cell membranes (intraperiod lines) are held to each other by tight junctions that not only contain the usual
proteins, claudins and zonula occludens proteins, but also contain connexin 32 (Cx32).
• the region of the myelin sheath where the myelin wrapping ends farthest from the axolemma (axon membrane) is the external mesaxon.
• the region of the myelin sheath where the myelin wrapping ends closest to the axolemma is the internal mesaxon.
• the intraperiod gap extends from the external to the internal mesaxon.
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cLINIcAL coNSIDERATIoNS
Multiple sclerosis, a disease of demyelination within the CNS, is common. Individuals 15 to 45 years old are affected, and it is approximately 1.5 times more common in females. Regions of the CNS that are demyelinated include the
cerebellum, white matter of the cerebrum, spinal cord, and cranial and spinal nerves. There are periods of multifocal inflammation accompanied by edema with demyelination of CNS axons. Each episode may lead to severe deterioration or malignancy or both within the affected nerves, and depending on areas affected, death may result within months. These attacks are followed by remissions lasting several months or decades.
Each episode causes the patient to lose vitality.
Multiple sclerosis is believed to be an inflammatory autoimmune disease resulting from the presence of an infectious agent.
Immunosuppressants combined with
corticosteroids and anti-inflammatory treatment are the therapies of choice.
radiation therapy involving the brain or spinal cord can lead to demyelination of the nerves in the pathway of the radiation beam. Also, the toxic substances used in chemotherapy can lead to demyelination of axons of the nervous system that may cause neurologic problems.
Guillain-Barré syndrome is an immune disorder resulting from recent respiratory or gastrointestinal infection. It produces inflammation and
demyelination of peripheral nerves causing muscle weakness in the extremities. The onset is early and peaks within a few weeks. Early diagnosis with autoimmune globulin treatments and physical therapy are usually recommended.
Figure 9.5 the fine structure of a myelinated nerve fiber and its schwann cell. (From Gartner LP, Hiatt JL: Color Textbook of Histology, 3rd ed. Philadelphia, Saunders, 2007, p 192.) Mesaxon
Basal lamina
Schwann cell
Figure 9.6 Diagrammatic representation of the myelin structure at the node of Ranvier of axons in the cns and the Pns (inset). (From Gartner LP, Hiatt JL: Color Textbook of Histology, 3rd ed. Philadelphia, Saunders, 2007, p 197.)
Oligodendrocyte Myelinated nerve fibers Node of Ranvier
Axon
Schwann cell
Plasmalemma of Schwann cell Axon
Myelin sheath
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