Ovarian hormones ameliorate memory impairment, cholinergic deficit, neuronal apoptosis and astrogliosis in a rat model of Alzheimer's disease

Hu,Zhiying; Yang,Yang; Gao,Keqiang; Rudd,John  A.; Fang,Marong

doi:10.3892/etm.2015.2868

Ovarian hormones ameliorate memory impairment, cholinergic deficit, neuronal apoptosis and astrogliosis in a rat model of Alzheimer's disease

Authors:
- Zhiying Hu
- Yang Yang
- Keqiang Gao
- John A. Rudd
- Marong Fang
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Affiliations: Department of Obstetrics and Gynecology, Hangzhou Red Cross Hospital, Hangzhou, Zheijiang, P.R. China, Institute of Neuroscience, Zhejiang University School of Medicine, Hangzhou, Zhejiang, P.R. China, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, P.R. China
Published online on: November 13, 2015 https://doi.org/10.3892/etm.2015.2868
Pages: 89-97
Copyright: © Hu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Ovarian hormones, including progesterone (P4) and 17 β-estradiol (E2), have been shown to affect memory functions; however, the underlying mechanism whereby ovarian hormone replacement therapy may decrease the risk of Alzheimer's disease (AD) is currently unclear. The present study aimed to investigate the effects of P4 and E2 on spatial and learning memory in an ovariectomized rat model of AD. β‑amyloid (Aβ) or saline were stereotaxically injected into the hippocampus of the rats and, after 1 day, ovariectomy or sham operations were performed. Subsequently, the rats were treated with P4 alone, E2 alone, or a combination of P4 and E2. Treatment with E2 and/or P4 was shown to improve the learning and memory functions of the rats, as demonstrated by the Morris water maze test. In addition, treatment with E2 and P4 was associated with increased expression levels of choline acetyltransferase and 5‑hydroxytryptamine receptor 2A (5‑HT2A), and decreased expression levels of the glial fibrillary acidic protein in the hippocampus of the rats. Furthermore, E2 and P4 treatment significantly attenuated neuronal cell apoptosis, as demonstrated by terminal deoxynucleotidyl transferase dUTP nick end labeling assays; thus suggesting that the ovarian hormones were able to protect against Aβ‑induced neuronal cell toxicity. The results of the present study suggested that the neuroprotective effects of P4 and E2 were associated with amelioration of the cholinergic deficit, suppression of apoptotic signals and astrogliosis, and upregulation of 5‑HT2A expression levels. Therefore, hormone replacement therapy may be considered an effective strategy for the treatment of patients with cognitive disorders and neurodegenerative diseases.

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