Recent work has suggested that 5α-reduced metabolites of testosterone may contribute to the neuroprotection conferred by their parent androgen, as well as to sex differences in the incidence and progression of Alzheimer's disease (AD). This study investigated the effects of inhibiting 5α-reductase on object recognition memory (ORM), hippocampal dendritic morphology and proteins involved in AD pathology, in male 3xTg-AD mice. Male 6-month old wild-type or 3xTg-AD mice received daily injections of finasteride (50 mg/kg i.p.) or vehicle (18% β-cyclodextrin, 1% v/b.w.) for 20 days. Female wild-type and 3xTg-AD mice received only the vehicle. Finasteride treatment differentially impaired ORM in males after short-term (3xTg-AD only) or long-term (3xTg-AD and wild-type) retention delays. Dendritic spine density and dendritic branching of pyramidal neurons in the CA3 hippocampal subfield were significantly lower in 3xTg-AD females than in males. Finasteride reduced CA3 dendritic branching and spine density in 3xTg-AD males, to within the range observed in vehicle-treated females. In the CA1 hippocampal subfield, dendritic branching and spine density were reduced in both male and female 3xTg-AD mice, compared to wild type controls. Hippocampal amyloid β levels were substantially higher in 3xTg-AD females compared to both vehicle and finasteride-treated 3xTg-AD males. Site-specific Tau phosphorylation was higher in 3xTg-AD mice compared to sex-matched wild-type controls, increasing slightly after finasteride treatment. These results suggest that 5α-reduced neurosteroids may play a role in testosterone-mediated neuroprotection and may contribute to sex differences in the development and severity of AD.

中文翻译：

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抑制5α还原酶损害认知能力，改变树突形态并增加雄性3xTg-AD小鼠海马中的Tau磷酸化。

最近的研究表明，睾丸激素的5α还原代谢产物可能有助于其父母雄激素赋予的神经保护作用，以及阿尔茨海默氏病（AD）发病和进展的性别差异。这项研究调查了抑制5α-还原酶对雄性3xTg-AD小鼠的对象识别记忆（ORM），海马树突形态和与AD病理相关的蛋白质的影响。雄性6个月大的野生型或3xTg-AD小鼠每天注射非那雄胺（50 mg / kg ip）或溶媒（18％β-环糊精，1％v / bw）注射20天。雌性野生型和3xTg-AD小鼠仅接受载体。在短期（仅3xTg-AD）或长期（3xTg-AD和野生型）保留延迟后，非那雄胺治疗可差异性影响男性ORM。在3xTg-AD女性中，CA3海马亚区中的树突棘密度和锥体神经元的树突分支明显低于男性。非那雄胺降低了3xTg-AD雄性的CA3树突分支和脊柱密度，至在接受媒介物处理的雌性中观察到的范围内。与野生型对照组相比，在雄性和雌性3xTg-AD小鼠中，CA1海马亚区的树突状分支和脊柱密度均降低。与媒介物和非那雄胺治疗的3xTg-AD雄性相比，3xTg-AD雌性海马淀粉样蛋白β水平明显更高。与性别匹配的野生型对照相比，3xTg-AD小鼠的位点特异性Tau磷酸化更高，在非那雄胺治疗后略有增加。