Impact of neurosteroids on impaired neurogenesis of Alzheimer's disease

• 1、School of Basic Medical Sciences,Nanjing Medical University
• 2、School of Basic Medical Sciences,Nanjing Medical University,Nanjing 210029

Abstract：Alzheimer's disease (AD) is a progressive neurodegenerative disease that is characterized by damages selective in the cognitive function. Adult mammalian neural stem cells can differentiate into functional activity of neurons (neurogenesis). It is indicated that the new neurons can replace the degenerated neurons to improve the cognitive impairment in AD. However, the survival and maturation of hippocampal newborn neuronal cells are impaired in AD. Neurosteroid pregnenolone-sulfate (PREGS) or dehydroepiandrosterone (DHEA) enhances adult hippocampal neurogenesis. Objective: Effects of PREGS or DHEA treatment on the impaired neurogenesis were investigated in 8-month-old male APPswe/PS1dE9 transgenic (APP/PS1) mice that shows amyloid plaques and spatial cognitive deterioration. Methods: Using Morris water maze and immunohistochemical staining, the spatial memory function, the mitosis of progenitor cells, the neurite growth and survival of newborn neurons were examined in 8-month-old APP/PS1 mice. Results: In the hippocampal dentate gyrus of APP/PS1 mice the proliferation of progenitor cells increased, while the neurite growth and survival of newborn neuronal cells were observably impaired. Either PREGS or DHEA could perfectly rescue the hypoplastic neurite of newborn neurons in APP/PS1 mice, although neither of them affected the over-proliferation of progenitor cells. Notably, PREGS but not DHEA could protect the survival of newborn neuronal cells to approach maturation in APP/PS1 mice. The protection of hippocampal neurogenesis in APP/PS1 mice treated with PREGS was accompanied by an improvement of spatial memory.

Keywords： phsiology Alzheimer's disease (AD) β-amyloid peptides (Aβ) pregnenolone sulfate (PREGS) dehydroepiandrosterone (DHEA) neuroregeneration