Neuroactive Molecules in the Brains of Nonhuman Primates and Their Therapeutic Application to Neurodegenerative Disorders

Motoharu Hayashi

The central nervous system (CNS) is more complex in primates, including humans, than in other mammals. Primates have particularly larger, visual, prefrontal, parietal, and temporal cortices. This expansion may cause the higher visual and learning abilities. Furthermore, transient increases in axons and synapses are unique characteristics in the primate neocortex during development. To understand these processes from the molecular level, we have focused on growth-associated proteins, GAP-43 and SCG-10 and on neurotrophins such as BDNF and its TrkB receptor. We have found that the development of truncated TrkB, which lacks the tyrosine kinase domain, correlated well with the downregulation of GAP-43 and SCG-10 expression. This downregulation seems to result in the elimination of axons in primate neocortices during development. The highest levels of BDNF protein in the primate visual and prefrontal cortices occur between 1 and 6 months of age, when the number of synapses is highest, suggesting that BDNF is a candidate molecule for the development of synapses in the primate neocortex. In aging primates, expression of BDNF and somatotstatin (SRIF) decreased and Aβpeptides accumulated. Similar cellular and molecular changes have been found in the brains of patients with Alzheimer's disease, suggesting that aged monkeys are good model animals for this disease. Furthermore, gene therapies for various neurotrophins may be used in the future to cure neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, HuntingtonĄÇs disease, and schizophrenia.

Central Nervous System Agents in Mdedicinal Chemistry 8, 220-228. (2008)

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