Developmental processes and the pathophysiology of mental retardation

Abstract

Some of the known causes of mental retardation (MR) include genetic abnormalities, exposure to toxins, many types of infections, malnutrition, brain trauma, and even extreme postnatal neglect. The developing brain is vulnerable to these insults during all the identifiable stages of brain development. Gastrulation leads to the formation of the three germ layers, and neurulation leads to the formation of the central and peripheral nervous systems. Cells formed in these nervous systems migrate from their site of origin to their final position in the brain and periphery. They then differentiate into structures and cells with the final functional properties of nerve cells during prenatal and postnatal activity-dependent periods. All reported causes of MR also produce other types of impairments, which may include physical, neurologic, or psychiatric manifestations and disabilities. The authors suggest that if the biological basis of normal learning, memory, and adaptive behavior can be reduced to cellular events, regulation of synaptic strength would be the most fundamental basis of neural plasticity and learning. Thus, understanding conditions or events that impair or delay development of brain mechanisms for plasticity, learning, and memory is an important first step in understanding the conditions that prevent their development. This article focuses on the particular aspects of neuroembryology, differentiation, and synaptic modification that are particularly vulnerable to developmental insults that cause MR. The most effective types of behavioral and other interventions in the future may be improved by knowledge of the rules that regulate the development of brain plasticity mechanisms in experimental animals. © 1997 Wiley-Liss, Inc.