Due to the increasing cases of neurodegenerative diseases in recent years, the eventual goal of nerve repair is very important. One approach for achieving a neuronal cell induction is by regenerative pharmacology. Nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) are neurotrophins that play roles in neuronal development, differentiation, and protection. On the other hand, dehydroepiandrosterone (DHEA) is a neurosteroid which has multiple actions in the nervous system. DHEA could be an important agent in regenerative pharmacology for neuronal differentiation during tissue regeneration. In this study, we investigated the possible role of DHEA to modulate NGF and BDNF production. The in vivo level of neurotrophins expression was demonstrated by ELISA in rat harvested brain cortex. Also neurotrophins expression after DHEA treatment was revealed by the increased neurite extension, immunostaining, and BrdU labeling in rats. Anti-NGF and anti-BDNF antibodies were used as suppressive agents on neurogenesis. The results showed that NGF and BDNF are overproduced after DHEA treatment but there is not any overexpression for NT-3 and NT-4. Also DHEA increased neurite extension and neural cell proliferation significantly. Overall, DHEA might induce NGF and BDNF neurotrophins overproduction in cortical neurons which promotes neural cell protection, survival, and proliferation. 1. Introduction The central nervous system (CNS) is composed of an orchestrated control of cell proliferation, motility and maturation of neuronal and glial cells, axonal growth, neurite outgrowth, and the design of synapses. Neurotrophins are originally identified as important peptides involved in the development of nervous system and could determine neuronal differentiation phenotype. The neurotrophins that influence neural development include nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), NT-4/5, and neurotrophin-6 (NT-6) [1, 2]. Nerve growth factor (NGF) is the most important target-derived trophic factor for basal forebrain cholinergic neurons (BFCNs) [3]. These are small proteins, which share more than 50% sequence homology. These factors could enhance survival, proliferation, and differentiation of postmitotic neurons [4]. It is known that they could increase in neuronal numbers and neurite outgrowth [5]. So it is important to find molecules that promote overproduction of the neurotrophins. In this study, we focused to understand the induction of NGF and BDNF through dehydroepiandrosterone (DHEA) as a pharmacological agent.
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