Title:Neurosteroid PREGS Protects Neurite Growth and Survival of Newborn Neurons in the Hippocampal Dentate Gyrus of APPswe/PS1dE9 Mice
Volume: 9
Issue: 3
Author(s): Bingzhong Xu, Rong Yang, Fei Chang, Lei Chen, Guiqing Xie, Masahiro Sokabe and Ling Chen
Affiliation:
Keywords:
neurosteroid; pregnenolone sulfate (PREGS); dehydroepiandrosterone (DHEA); neurogenesis; β-amyloid peptides
(Aβ); Alzheimer’s disease (AD)
Abstract: Neurosteroids pregnenolone-sulfate (PREGS) and dehydroepiandrosterone (DHEA) have been shown to enhance
neurogenesis in the hippocampal dentate gyrus (DG) of adult rodents. In Alzheimer’s disease (AD) brain, the levels
of these neurosteroids are known to be altered compared to age-matched non-demented controls. The aim of this study
was to examine the effects of PREGS and DHEA on the hippocampal neurogenesis in 8-month-old male APPswe/PS1dE9
transgenic (APP/PS1) mice that show amyloid plaques and impaired spatial cognitive performance. In the DG of APP/PS1
mice the proliferation of progenitor cells was increased, while the neurite growth and survival of newborn neuronal cells
were markedly impaired. Treatment with PREGS or DHEA rescued perfectly the hypoplastic neurite of newborn neurons
in APP/PS1 mice, while neither of them affected the over-proliferation of progenitor cells. Notably, the administration of
PREGS, but not DHEA, to APP/PS1 mice could protect the survival and maturation of newborn neuronal cells, which was
accompanied by the improvement of spatial cognitive performance. The results indicate that treatment of AD like brains
of APP/PS1 mice with PREGS might protect the hippocampal neurogenesis, leading to the improved spatial cognitive performance
