Cells of the Nervous System


Cells of the Nervous System

The nervous system contains a complex organization of over a trillion cells. Many cells rapidly communicate with each other by producing electrical impulses that are sent from one cell to another. The nervous system is composed of two major types of cells: neurons and glia (or glial cells). Neurons are designed to transmit information rapidly from one cell to another. They are responsible for the functions normally associated with the nervous system, such as sensory perception and movement. Glia, on the other hand, help maintain the environment surrounding neurons and aid in their ability to transmit information rapidly.


Neurons 

 

Neurons are the cells that encode information within the nervous system. These cells transmit information from one region of the brain to another.  Their anatomical structure is highly specialized to carry out these functions. Neurons are composed of four functionally distinct components: the soma, dendrites, the axon, and axon terminals. The soma is the cell body of a neuron. It contains the molecular machinery required to produce and package proteins used in other parts of the cell to maintain a variety of cellular functions. The membrane of the soma also has receptors to bind neurotransmitter molecules that are released by other nerve cells.  Activation of receptors on the soma membrane is an important part of cell-to-cell communication in the nervous system. Dendrites are fiber-like structures that branch out from the cell body. Dendrites also express receptors on their surface membranes to provide extensive areas for cell-to-cell communication.  

The axon is a long fiber-like structure that extends from the soma to make contact with other nerve cells. The initial segment or axon hillock of the axon is a sensitive region that triggers the discharge of electrical impulses. In many nerve cells, sections of the axon are surrounded by myelin. The areas in between the segments of insulation are called nodes of Ranvier. As we will later in the textbook, the nodes of Ranvier enhance the conduction of electrical impulses. The axons end at terminals, which make contact with other nerve cells at junctions called synapses.  It is at the synapse where neurotransmitters are released from one neuron to bind to receptors on other neurons.  This is accomplished by an electrochemical process where the electrical impulse called an action potential is conducted from the initial segment to the axon terminal to release neurotransmitters for binding with postsynaptic receptors.

Specialized Subcellular Structures   

As with other types of cells, the nucleus of nerve cells contains DNA the genetic information needed for the synthesis of specific proteins. Some proteins, for example, are involved in the formation of new functional connections with other cells as a result of signals from afferent inputs or during the process of regeneration.

 

In neurons the nucleus is relatively quite large. A substantial portion of the genetic information contained within the genome is continually transcribed by neurons. Based on hybridization studies, it is estimated that one third of the genome is actively transcribed, producing more mRNA than any other organ in the body. Because of the high level of transcriptional activity, the nuclear chromatin is in the form of dispersed chromatin. In contrast, the chromatin in non-neuronal cells in the brain such as glia is found in clusters on the internal face of the nuclear membrane. The neuronal nucleus also contains one or two nucleoli, which often have attached electron-dense bodies. One of the dense bodies associated with the nucleolus in females is the Barr body, which is the condensed chromatin of the inactive X-chromosome.

Most of the proteins formed by free ribosomes and polyribosomes remain within the cell, while proteins formed by rough endoplasmic reticulum (RER) are exported. Polyribosomes and RER are found predominantly in the soma of neurons. Axons contain no RER and are unable to synthesize proteins. Dendrites, on the other hand, contain ribosomes and RNA, and are thought to play an important part in the plastic modulation of dendritic structure and function.  It is thought that the synaptic plasticity or modifiability of synaptic-dendritic interactions represent the anatomical and biochemical basis of learning and memory.

The smooth endoplasmic reticulum is involved in the intracellular storage of calcium. Smooth endoplasmic reticulum within neurons binds calcium and maintains the intracellular cytoplasmic concentration at a low level of 0.1 µmoles. Prolonged elevation of intracellular calcium has been shown to lead to neuronal death and degeneration.

In neurons the Golgi apparatus is found in the soma. As in other types of cells, this structure is engaged in the terminal glycosylation of proteins synthesized in the RER. The Golgi apparatus takes proteins produced for exportation in the RER and forms protein-containing vesicles. These vesicles are released into the cytoplasm, where some are carried by axoplasmic transport to the axon terminals.

The Neuronal Cytoskeleton 


 

The transport of proteins from the Golgi apparatus and the highly specialized form of the neuron are dependent on the internal framework of the cytoskeleton.  The neuronal cytoskeleton is made of microfilaments, neurofilaments, and microtubules (Fig. 7-8).  Microfilaments are composed of actin, a contractile protein commonly found in muscle.  They are 4-5 nm in diameter, and in neurons they are found in dendritic spines and growth cones.  

Neurofilaments, on the other hand, are found in axons and dendrites and are thought to provide structural rigidity.  They are not found in the growing tips of axons and dendritic spines, which are more dynamic structures.  Neurofilaments are about the size (10 nm diameter) of the intermediate filaments found in other types of cells.  However, intermediate filaments in other cell types consist of one protein, while neurofilaments are composed of three proteins (70 kd, 140 kd, and 220 kd in size).  The core of the filament consists of the 70 kd protein, similar to intermediate filaments in other cells.  The two other neurofilament proteins are thought to be side arms that interact with microtubules for movement of organelles within the neuron.

Microtubules are responsible for the rapid movement of material in axons and dendrites. They are 23 nm in diameter and are composed of tubulin with molecular weights of 52 and 56 kd. In neurons, microtubules have accessory proteins called microtubule-associated proteins (MAPS). Dendrites have high molecular weight MAPS, while axons have low molecular weight MAPS; these two types of MAPS are thought to determine whether material is distributed to dendrites or to axons.

In neurons, energy producing organelles called mitochondria are highly concentrated in the region of axon terminals. They produce adenosine triphosphate (ATP), which is required as a source of energy for many cellular processes. In the axon terminal the mitochondria not only provide a source of energy for the process of synaptic transmission but also provide substrates for the synthesis of certain neurotransmitter chemicals such as the glutamate. In addition, enzymes involved in the degradation of other types of neurotransmitter chemicals are embedded in the outer membrane of the mitochondria. Thus the role of mitochondria in the neuron is multifunctional and is a key player in the loss of neurons via apoptosis or programmed cell death, as seen in many neurodegenerative diseases.



Axonal and Dendritic Transport Mechanisms   

The shapes of most cells in the body are relatively simple in comparison to the complexity of neurons, with their elaborate axonal and dendritic processes. Because of the length of nerve cell processes, however, neurons have developed specialized mechanisms to transport proteins, organelles, and other cellular material along the length of axons and dendrites needed for the maintenance of the cell. These transport mechanisms are capable of moving cellular components along fiber processes in an anterograde direction away from the soma, or in a retrograde direction toward the soma. Kinesin, a microtubule associated protein, is involved in anterograde transport of organelles and vesicles via the hydrolysis of ATP. Retrograde transport, on the other hand, is mediated by another microtubule associated protein called dynein.

In the axon, anterograde transport occurs at both a slow and a fast rate.  The rate of slow axonal transport is 1 to 2 mm/day.  Structural proteins such as actin, as well as neurofilaments and microtubules, are transported at this speed.  The rate of fast axonal transport is 400 mm/day.  Fast transport mechanisms are utilized by organelles, vesicles, and membrane glycoproteins needed at the synaptic terminal.  Another feature that distinguishes fast from slow transport mechanisms is that fast transport requires Ca2+, glucose, and ATP (i.e., it is dependent upon oxidative metabolism).

In dendrites, anterograde transport occurs at a rate of 0.4 mm/day, and like fast transport, it also requires ATP.  Dendritic transport appears to be involved in the movement of ribosomes and RNA, suggesting that protein synthesis occurs within dendrites.

In retrograde axonal transport, material is moved from terminal endings to the cell body. This provides a mechanism for the cell body to sample the environment around its synaptic terminals. In so some neurons, maintenance of synaptic connections depends on the transneuronal transport of trophic substances, such as
nerve growth factor (NGF), across the synapse. After transport to the soma, NGF activates mechanisms gene expression for protein synthesis.


The Growth Cone in Nerve Fiber Development and Regeneration  

 

One of the major features distinguishing nerve cell differentiation and growth from that of other cell types is the outgrowth of the axon from the nerve cell body, in a specific direction and along a specific pathway, to form synaptic connections with specific targets. The growth of axons is determined largely by interactions between the growing axon and the tissue environment. At the leading edge of a growing axon is the growth cone. Growth cones are structures that give rise to protrusions called filopodia. Growth cones contain actin, a contractile protein, and are quite motile, with filopodia extending and retracting at a rate of 6 to 10 µm/min. Newly synthesized membranes in the form of vesicles are also found in the growth cone and fuse with it as it extends. As the growth cone elongates, microtubules and neurofilaments are added to the distal end of the fiber and partially extend into the growth cone. They are transported to the growth cone via the process of slow axonal transport.

The direction of axonal growth is directed in part by cell adhesion molecules (CAMs). CAMs are glycoproteins that are expressed on cell surfaces to promote cell adhesion. Neuron-glia-CAM (Ng-CAM) is expressed in postmitotic neurons and is particularly prominent in growing neurites (axons and dendrites); these neurites migrate along certain types of glial cells that provide a guiding path to target sites. The secretion of tropic factors by target cells also influences the direction of axon growth. Once the proper target site is reached, and synaptic connections are formed, the processes of growth cone elongation and migration are terminated.

During development, axon terminals are found on target cells in excess of the numbers seen after the nervous system has matured. Cells in the lateral geniculate nucleus of the thalamus, for example, receive both ipsi- and contralateral inputs during development. In the adult, however, these cells no longer receive inputs from both eyes but only from either the ipsilateral or contralateral input. This loss of synaptic contacts is a result of a selection process whereby the most active inputs predominate and survive at the expense of less active synaptic contacts.

Growth cones are found not only during development but also during the regeneration of nerve fibers. When a nerve fiber is cut, the distal end degenerates while the fiber segment proximal to the soma develops growth cones for elongation and extension. Regeneration of an axon therefore occurs at a rate of 1 mm/day, the rate of slow axonal transport.

Glia – Oligodendroglia, Astroglia, and Microglia 

 

There are three basic types of glial cells in the CNS: oligodendroglia, astroglia, and microglia. Oligodendroglia wrap themselves around axons to form myelin, layers of lipid membrane, which insulate the axon to prevent the passage of ions through the axonal membrane.  In between the myelinated regions of the axon are nodes of Ranvier.  The exposed nerve membranes at these nodes contain a high concentration of channels that regulate the passage of ions the are responsible for the generation of electrical impulses called action potentials. Disease processes can sometimes lead to the loss of oligodendroglia as in the case of multiple sclerosis resulting in a variety of neurological deficits.   Typically, one oligodendroglia will myelinate many axons in the central nervous system.  In the peripheral nervous system, Schwann cells play a similar role to oligodendroglia in forming myelin around nerve fibers. In contrast to oligodendroglia, however, one Schwann cell will myelinate only one axon in the peripheral nervous system (PNS). The Schwann cell has been shown to play an important role in the regeneration of damaged nerve processes in the peripheral nervous system.  Interestingly, molecules expressed by oligodendroglia inhibit regeneration, and nerve fiber damage in the central nervous system (CNS) is therefore typically irreparable.

 

Astroglia, also called astrocytes, are star-shaped cells which exhibit the greatest diversity of function among glial cells in the CNS.  One type of astroglia, the fibrous astrocyte, is found in areas containing predominantly nerve fibers.  It is called fibrous because of the large number of intermediate filaments found in glial cells.  Protoplasmic astrocytes are similar to fibrous astrocytes but have fewer filaments.  They are found in areas containing predominantly nerve cell bodies, dendrites, and synapses.  Both types form "glial end-feet" on blood vessels.  The anatomical relationship between glial end-feet and blood vessels form the so-called blood-brain-barrier that prevents unwanted substances in the circulatory system from penetrating the brain. A key component of the blood-brain-barrier are the tight junctions between the endothelial cells that form the lumen of the blood vessels.

During injury to the brain astrocytes proliferate and transform into reactive astrocyte.  In this activated state they remove degenerating debris by the process of phagocytosis.  After removal of debris astroscytes form glial scars that are typically seen after brain injury.

Astrocytes regulate the concentration of K+ ions in the extracellular space by uptake and redistributing to other astrocytes. This is accomplished by the transport of K+ ions through the gap junctions that link networks of glial cells. This type of spatial buffering is needed to maintain the constant extracellular environment of K+ that is critical to the function of neuron-generated electrical impulses.

Astrocytes also regulate the concentration of neurotransmitters that are released by nerve cells during the process of synaptic transmission. This uptake by glial cells is needed to terminate synaptic transmission and prevent the flooding of neurotransmitters between nerve cells.

Astrocytes are also thought to be involved in the maintenance of interstitial pH, which is required for the optimal function of many cellular processes. As in other organ systems, the enzyme carbonic anhydrase plays a critical part in acid-base balance. In the central nervous system, this enzyme is found mainly in astrocytes and oligodendroglia.

  Microglia differ from oligodendroglia and astrocytes in that they are not derived from neural progenitor cells but from bone marrow.  They function similar to macrophage cells of the immune system that are capable of engulfing infected cells and processing proteins for recognition by immune cells. After injury to the nervous system, microglia are transformed from a quiescent to an activated state, migrate to the site of damage where their main function is the removal of cellular debris by phagocytosis and antigen presentation. In the activated stated the secrete cytokines that are involved in the inflammatory processes that recruit immune cells to sites of injury.

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