Brain development synaptogenesis

FAS is now considered to be a leading cause of mental retardation in the general population. Figure 7.13 shows the comparison between brain growth spurt in humans and rats. It should be noted that brain development characterized by accelerated synaptogenesis, neuronal proliferation, and myelination commences prenatally during the third trimester in humans and continues into early postnatal life. 

In fetal lambs the T3 receptor concentration increases 2.6-fold from the 50th day to the 82d day of gestation. From 82 to 100 days, the concentration remained constant [54]. In these different species, the changes in receptor numbers correspond to critical periods of brain development (neuroblast proliferation, synaptogenesis). 

The activity of the malate-aspartate shuttle increases during development in parallel with synaptogenesis, which is consistent with the high activity and importance of this shuttle in neurons and synaptic terminals. Evidence of highly regulated malate-aspartate shuttle in adult human brain has been documented [73 and references therein]. 

Nicholson JL, Altman J (1972) The effects of early hypo- and hyperthyroidism on the development of the rat cerebellar cortex. II. Synaptogenesis in the molecular layer. Brain... 

Developmental malformations, impaired neuronal innervation, diminished parenchymal mass, metabolic compromise, and diminished dopamine tone in the frontal cortex typify schizophrenia but have little to do with dopamine receptors. The diminished transcription of genes for synaptogenesis, myeli-nation, metabolism, and development in the schizophrenic brain (8) may explain these impairments and are beginning to provide a novel set of targets for therapeutic intervention. 

In the adult nervous system, neurotransmitters are mainly working as cell-cell signalling molecules in the synapses. However, during development they also affect further differentiation, e.g., expression of different neurotransmitters and receptors. Exposure to chemicals that modify neurotransmitter systems, like psychopharmaceuticals and pesticides, may therefore have serious effects on the developing nervous system and the level of the neurotransmitters in the brain. Other chemicals that are reported to modify synaptogenesis are nicotine [87], ethanol [88], toluene [89], methyl mercury [90], parathion [91] and PCBs [92],... 

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