In our previous issue, we attempted to show briefly how an organism as complex as the human body begins as a single cell or two, develops in the embryo with cells differentiating into vital functioning systems and organs of particular interest to us in the nervous system and its many components. We learn that the fate of nerve cells, in combination with other neurons, depends largely on whether they are successful in establishing viable connections with peripheral organs. If an organ is transplanted into a developing embryo, the organ is likely to be supplied with nerves from a nerve center in which the number of cells seem to increase. But, no additional cells are actually provided. Cells that would have otherwise degenerated, remain active and tend to differentiate into functional neurons, thus satisfying the demand created by the new organ.
Anatomy of the Developing Human Nervous System
Most all neurons are generated in the embryo and are not replaced after birth. Morphologically, the genesis of the neural plate ushers in the initial appearance of the nervous system at about 18 days after conception. Functionally, the nervous system appears with the first sign of reflex activity during the second prenatal month. By the third month, many reflexes can be elicited in the head, trunk, and extremities.
During its development, it is estimated that the nervous system generates an average of 2.5 million neurons per minute during the entire prenatal life in order to produce an estimated one trillion neurons present in the mature brain. This incredible growth includes the formation of neuronal circuits that comprise 100 trillion synapses. Remember that each potential neuron is ultimately connected with either a selected set of other neurons or specific targets such as sensory endings. The synaptic connections with other neurons are made at precise locations on the cell membranes of the target neurons. Rather than these events being considered as the exclusive product of the genetic code, the differentiation and subsequent development of embryonic cells into mature neurons and glial cells are achieved by two sets of influences: 1) specific subsets of genes, and 2) environmental stimuli from within and outside of the organism.
The Spinal Cord: It's Structure and Function
Neurons are not exclusively outgrowths of the brain and spinal cord. Many neuronal components are outgrowths of other neural cell bodies located in ganglia (masses). There are three main classifications of ganglia: spinal, cranial, and ganglia of the autonomic nervous system.
The spinal ganglia fibers that connect peripheral organs to the spinal cord constitute the sensory pathways in the spinal nerves. The spinal nerves have motor components that activate skeletal muscles and are derived from the neural-crest cells (the loose mesenchyme-like tissue between the neural tube and skin, after separation of the two.)
It has long been accepted that oligodendrocytes and Schwann cells considered as neuralgia (or nerve glue) produce and maintain the myelin sheath that covers neuronal axons. Studies have indicated that some constituent of the axonal surface tends to stimulate Schwann cell proliferation. Nodes of Ranvier, important in the transmission of nerve impulses, are exposed sections between segments of myelin wrapping.
Neuroglial cells have another well-defined function. Following trauma to the CNS, astrocytes are found to divide and occupy the spaces left by injured neurons.
After neurons in the PNS are cut, the fibers are shown to degenerate and then eventually regenerate in such a way as to return to their original target sites. Apparently Schwann cells that remain after nerve degeneration will mark the route. Astrocytes also seem capable of providing route direction during development of the CNS. Thus we see that neuroglia plays a significant role in neuronal organization.
Astrocytes have also been shown to have high-affinity uptake systems for such neurotransmitters as glutamate and gamma-aminobutyric acid (GABA)...so important in the modulation of synaptic transmission. The function of uptake systems is to terminate neurotransmitter activity at the synapses. When motor nerves are injured and their terminals degenerate, their original sites become occupied by Schwann cells that can receive current, and evoke neurotransmitter release. Thus, the synthesis of neuro-transmitters by neurons apparently requires the presence of neuroglial cells.
It has been demonstrated that neuroglial cells in vitro do indeed have voltage-sensitive properties similar to those of excitable neurons. However, there is no proof available of electrical activity similar to that occurring in neurons having ever been generated in neuroglial cells in vivo.
There appear to be two main groups of neuroglia:
The neural crest in embryo contributes to the formation of the meningeal covering of the brain, is the source of Schwann cells, and gives rise to paired chains of sympathetic nerve ganglia, as well as to certain cells of the adrenal gland.
Schwann cell layers make up the myelin sheath in both the PNS and CNS. Myelin sheaths that cover nerve fibers are white. Nonmyelinated nerve fibers are gray.
Acquired demyelinating neuropathies often damage the smallest blood vessels that supply the nerves. Probably still the most common cause of neuropathy in the world is leprosy.
External compression of a nerve is a common example of ischemic neuropathies. Persistent compression can cause the Schwann cells to migrate. Compression of spinal nerve roots can require precise surgical intervention in order to release the entrapped nerve.
The neuromuscular junction is a point of contact between the motor nerve and the muscle. The neural signal (electrical impulse) is conducted from the motor neuron in the spinal cord, along the axon to its destination at the neuromuscular junction. In humans, each muscle fiber is innervated by a single motor nerve fiber. As the nerve approaches the muscle, it loses its myelin sheath but remains partially covered by some Schwann cell processes. The narrow synapse that separates the nerve from the muscle contains the basal lamina which penetrates the muscle membrane of the subneural region. What is interesting about the neural signal is that no apparent electrical continuity exists between the nerve and the muscle. The signal is transmitted by chemical means that require both presynaptic and postsynaptic structures. As the axon conducts nerve impulses from the cell soma to the terminal, the terminal itself secretes chemical neurotransmitters. Synthesizing enzymes are formed by ribosomes in the soma and are transported down the axon to the terminal by the process known as axoplasmic flow, which occurs in both directions along the axon.
Specialized structures at the axon terminal form junctions with other neurons as well as with muscle cells. These junctions, called synapses are known to contain many organelles, most of which are filled with neurotransmitters.
The basal lamina in the synaptic cleft of nerve-muscle junctions serves to regulate the activity of neurotransmitters.
Cell-To-Cell Communication Via Chemical Signaling
The three types of chemical signaling are:
Receptors are specific proteins on the surface or in the cytoplasm of a cell that are necessary in order for a cell to respond to an extracellular signal. Cells may contain a variety of specific receptors that allow them to respond to an array of chemical agents.
An event within the cell is induced by the binding of chemical agents to their corresponding receptors. When cell surface receptors are occupied, they can work in several ways. Some activate membrane enzymes. Some enter the cell while still bound to the chemical agent. Other receptors open membrane channels, allowing a flow of ions that can change the electrical properties of the membrane.
A more rapid form of cell communication, probably of an electrical nature, occurs in invertebrate, and particularly fish nervous systems. Instead of a synaptic gap, they have gap junctions which are direct channels between neurons that establish a continuity between the cytoplasm of adjacent cells and a structural symmetry between the pre- and post-synaptic sites. In these electrical transmissions, the ionic current flows directly through channels that couple the cells. Whereas, in chemical transmissions, the neurotransmitters pass from one cell to the other, stimulating the second cell to generate its own action potential.
We are taught that once neurons are destroyed, they are not replaced. Although severed axons will sprout growths from the cut end, they don't form effective connections in the spinal cord.
We are also taught that cut or damaged axons in the PNS can regrow and eventually re-establish effective connection with sensory organs or muscle fibers.
The spinal cord contains descending autonomic fibers that terminate upon visceral cell groups that innervate muscle cells. The descending autonomic fibers seem to begin mostly from nuclei in the hypothalamus, the oculomotor complex, and the locus ceruleus. Reticulospinal tracts, via the pons and medulla, are also known to give rise to descending fibers.
The neurotransmitters of the long ascending and descending tracts of the spinal cord have not been identified--with the exception of some descending autonomic pathways and the corticospinal tract. However, it is believed by many that glutamate and/or aspartate are probably the principal neurotransmitters of cortical projections.
What is known as the lower motor neuron unit or final common pathway, is composed of anterior horn cells and their axons projecting via the ventral root to striated muscle. Injury to the anterior horn cells or their projecting axons including ventral roots, is likely to result in paralysis and atrophy of the muscles innervated by these fibers.
Most all of the descending spinal systems have some influence on the lower motor neuron. But, overwhelming clinical significance of the corticospinal tract has caused it to be equated with the upper motor neuron unit.
Spinal Cord Lesions
Cutting of the dorsal roots will abolish all input supplied by these roots and interrupt segmental reflex arcs.
Neural degeneration is limited to the primary afferent fibers and does not involve intrinsic spinal neurons or their processes.
What is referred to as complete spinal cord transection will result in the immediate loss of all neural function below the level of the lesion. The loss refers to 1) all somatic sensation, 2) all motor function, 3) all visceral sensation, 4) all reflex activity, 5) all muscle tone, and 6) thermoregulatory control. This complete cessation of neural function below the lesion is called spinal shock. Spinal shock generally persists from 1 to 6 weeks, with an average of 3 weeks in humans. At the end of the spinal shock period, the Babinsky reflex (an extensor toe response to stroking the sole of the foot) may reappear. Usually beginning about 4 months post-injury there is a slow, gradual, and progressive increase in extensor muscle tone.
In general, degeneration resulting from so-called complete transection of the spinal cord follows a well-established pattern. Above the level of the lesion, ascending tracts degenerate. Below the lesion level, ascending tracts appear intact. In descending tracts, the reverse is observed.
Differentiation and Duplication of Genetic Material
Scientists tell us that no matter what the cell type, all of an organism's genes are present in each cell nucleus, and that differences between tissues are due to the selective expression of some genes and the repression of others. Some experiments show that any nucleus has the genetic information required for the growth of a developing organism. Cell differentiation seems to arise from the regulation of genetic activity, rather than from the destruction or removal of unselected genes. The only known exception to this rule comes from the immune system. There, a wide variety of antibody and receptor molecules are produced where segments of DNA in developing white blood cells are slightly rearranged.
The expression of a gene can be differentially regulated in different cell types at the molecular level in many ways. But, by the time cells reach a state of terminal, or final differentiation, they are normally very sharply different from one another. States of terminal differentiation are inherently stable and persistent probably as a result of a feedback mechanism in which the products of active genes act on those genes in order to maintain their activity, and on other genes to maintain their inactivity.
Each human chromosome consists of a long double helix, or spiral, each strand of which consists of more than 100 million nucleotides. In order for each cell's progeny to function and survive, before the cell can divide, it must completely and accurately duplicate the genetic information encoded in its DNA. This duplication of DNA is called DNA replication, and it is initiated by complex enzymes called DNA polymerases.
In embryonic differentiation, with each progressive sequence of states, the cell becomes committed to a narrower range of types into which it can develop, probably based on differentiated gene activity.
Adult human differentiation generally only occurs in renewal tissues where differentiated cells are constantly produced from an undifferentiated stem cell population. Most renewal tissues are epithelial (skin), but blood has renewal tissue whose differentiation is best understood by science. The different types of blood cells are erythrocytes (red blood cells), granulocytes, lymphocytes, monocytes, platelets, and fragments of giant megekaryocyte cells. All of these types of blood cells arise from a single type of stem cell found in bone marrow. Control over the number of terminal cell types occurs through the action of growth-promoting substances on each of the lines at a precursor stage when they are already commited. The level of cell commitment actually appears to be a random process. So the identification activity of growth-promoting substances is interesting study, especially in the development of the nervous system.
Internet Services Provided by
