Neural Growth and Regeneration

Tuesday, February 28, 2012

The elaborate networks of nerve cell processes that characterize the nervous system are remarkably similar in all human beings and depend upon the outgrowth of specific axons to specific targets. Development of the nervous system in the embryo begins with a series of divisions of undifferentiated precursor cells (stem cells) that can develop into neurons or glia. After the last cell division, each neuronal daughter cell differentiates, migrates to its final location, and sends out processes that will become its axon and dendrites. A specialized enlargement, the growth cone, forms the tip of each extending axon and is involved in finding the correct route and final target for the process.

As the axon grows, it is guided along the surfaces of other cells, most commonly glial cells. Which route is followed depends largely on attracting, supporting, deflecting, or inhibiting influences exerted by several types of molecules. Some of these molecules, such as cell adhesion molecules, reside on the membranes of the glia and embryonic neurons. Others are soluble neurotropic factors (growth factors for neural tissue) in the extracellular fluid surrounding the growth cone or its distant target. Once the target of the advancing growth cone is reached, synapses are formed. The synapses are active, however, before their final maturation occurs. This early activity, in part, determines their final use. During these early stages of neural development, which occur during all trimesters of pregnancy and into infancy, alcohol and other drugs, radiation, malnutrition, and viruses can exert effects that cause permanent damage to the developing fetal nervous system.

A normal, although unexpected, aspect of development of the nervous system occurs after growth and projection of the axons. Many of the newly formed neurons and synapses degenerate. In fact, as many as 50 to 70 percent of neurons die by apoptosis in some regions of the developing nervous system. Exactly why this seemingly wasteful process occurs is unknown, although neuroscientists speculate that in this way connectivity in the nervous system is refined, or "fine-tuned." The basic shape and location of existing neurons in the mature central nervous system do not change. The creation and removal of synaptic contacts begun during fetal development continue, however, albeit at a slow pace throughout life as part of normal growth, learning, and aging. Division of neuron precursor stem cells is largely complete before birth.