title: Metabolic alteration of neuroactive steroids and protective effect of progesterone in Alzheimer's disease-like rats.
abstract: A correlation between metabolic alterations of neuroactive steroids and Alzheimer's disease remains unknown. In the present study, amyloid beta (Aβ) 25-35 (Aβ25-35) injected into the bilateral hippocampus CA1 region significantly reduced learning and memory. At the biochemical level, hippocampal levels of pregnenolone were significantly reduced with Aβ25-35 treatment. Furthermore, progesterone was considerably decreased in the prefrontal cortex and hippocampus, and 17β-estradiol was significantly elevated. To our knowledge, this is the first report showing that Aβ25-35, a main etiological factor of Alzheimer's disease, can alter the level and metabolism of neuroactive steroids in the prefrontal cortex and hippocampus, which are brain regions significantly involved in learning and memory. Aβ25-35 exposure also increased the expression of inflammatory mediators, tumor necrosis factor-α and interleukin-1β. However, subcutaneous injection of progesterone reversed the upregulation of tumor necrosis factor-α and interleukin-1β in a dose-dependent manner. Concomitant with improved cognitive abilities, progesterone blocked Aβ-mediated inflammation and increased the survival rate of hippocampal pyramidal cells. We thus hypothesize that Aβ-mediated cognitive deficits may occur via changes in neuroactive steroids. Moreover, our findings provide a possible therapeutic strategy for Alzheimer's disease via neuroactive steroids, particularly progesterone.
authors.affiliation: Hebei Medical University, Shijiazhuang 050017, Hebei Province, China.
authors.forename: Sha
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Pharmacy, Bethune International Peace Hospital of Chinese PLA, Shijiazhuang 050082, Hebei Province, China.
authors.forename: Honghai
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Pharmacy, Bethune International Peace Hospital of Chinese PLA, Shijiazhuang 050082, Hebei Province, China.
authors.forename: Gai
authors.initials: G
authors.lastname: Xue
authors.affiliation: Hebei Medical University, Shijiazhuang 050017, Hebei Province, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Ma
authors.affiliation: Hebei Medical University, Shijiazhuang 050017, Hebei Province, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Wu
authors.affiliation: Hebei Medical University, Shijiazhuang 050017, Hebei Province, China.
authors.forename: Yabin
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Hebei Medical University, Shijiazhuang 050017, Hebei Province, China ; Department of Pharmacy, Bethune International Peace Hospital of Chinese PLA, Shijiazhuang 050082, Hebei Province, China.
authors.forename: Yanning
authors.initials: Y
authors.lastname: Hou
keywords: Alzheimer's disease; amyloid beta; cognition; neural regeneration; neuroactive steroids; neurodegenerative disease; neuroprotection; neuroregeneration; progesterone