ABSTRACT

The central nervous system (CNS) of primates, including humans, is more complex than the CNS of other mammals. In particular, the neocortex expanded during evolution. This has resulted in the emergence of higher cognitive abilities such as learning and memory in primates. Recent neurochemical and neuroanatomical methods have clarified the presence of various neuroactive molecules, such as neurotransmitters, neuropeptides, neurotrophic factors (neurotrophins), and growth-associated proteins in he neocortex of primates. These molecules participate in various physiological functions that occur not only during development, but also during the adult stage and the aging process. The inhibitory GABAergic system develops concomitantly with the increase of neuronal activities in the primate neocortex. In contrast, gene expressions of neuropeptide, somatotstatin (SRIF), and the growth-associated protein GAP43 are up-regulated during the embryonic stage and decline after birth. These developmental changes in the gene expressions of SRIF and GAP43 are regulated by one of the neurotrophins, brain-derived neurotrophic factor (BDNF), and its receptor (TrkB). The levels of truncated TrkB only increased after birth, which correlated with the decrease in the gene expressions of SRIF and GAP43. These down-regulations of SRIF and GAP43 seem to participate in the elimination of commissural axons in the primate neocortex. Moreover, the highest levels of BDNF protein in the various cerebral cortices occur between postnatal months 1 and 4, when the numbers of synapses are highest, suggesting that BDNF is involved in the synaptic development in primates. Although no significant numbers of neurons are lost during the normal aging process, a decrease in glutaminergic and cholinergic signalings and gene expressions of SRIF and BDNF are observed in the monkey neocortex and hippocampus. Recent findings that the gene expressions of neurotrophins are regulated by stress, learning, maternal care, and exercise indicate that these neuroactive molecules may be beneficial for the treatment of various neurological diseases, such as autism, depression, age-related cognitive decline, and Alzheimer’s disease.