期刊
NEUROBIOLOGY OF AGING
卷 32, 期 11, 页码 1964-1976出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2009.12.014
关键词
Neurosteroids; GABA-A receptors; Alzheimer's disease; Postmortem; Prefrontal cortex; Aromatase; Gene expression
资金
- Istituto Der-mopatico Immacolata (IDI-IRCCS)
- Santa Lucia Foundation (Santa Lucia-IRCCS), Rome, Italy
- Netherlands Institute for Neuroscience
Expression of the genes for enzymes involved in neurosteroid biosynthesis was studied in human prefrontal cortex (PFC) in the course of Alzheimer's disease (AD) (n = 49). Quantitative RT-PCR (qPCR) revealed that mRNA levels of diazepam binding inhibitor (DBI), which is involved in the first step of steroidogenesis and in GABAergic transmission, were increased, as were mRNA levels for several neurosteroid biosynthetic enzymes. Aromatase, 17 beta-hydroxysteroid dehydrogenase type 1 (HSD17B1) and aldo-keto reductase 1C2 (AKR1C2), were all increased in the late stages of AD. Several GABA-A subunits were significantly reduced in AD. Increased expression of aromatase in the PFC was confirmed by immunohistochemistry and was found to be localized predominantly in astrocytes. These data suggest a role for estrogens and allopregnanolone produced by astrocytes in the PFC in AD, possibly as part of a rescue program. The reduced gene expression of some synaptic and extra-synaptic GABA-A subunits may indicate a deficit of modulation of GABA-A receptors by neuro active steroids, which may contribute to the neuropsychiatric characteristics of this disease. (C) 2009 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据