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Estrogen Exerts Neuroprotective Effects in Vascular Dementia Rats by Suppressing Autophagy and Activating the Wnt/β-Catenin Signaling Pathway

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A Correction to this article was published on 17 June 2021

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Abstract

Vascular dementia (VD) is a clinical syndrome of acquired cognitive dysfunction caused by various cerebrovascular factors. Estrogen is a steroid hormone involved in promoting neuronal survival and in regulating many signaling pathways. However, the mechanism by which it confers neuroprotective effects in VD remains unclear. Here, we aimed to investigate the effect of estrogen on neuronal injury and cognitive impairment in VD rats. Adult female rats were randomly divided into four groups (sham, model, estrogen early and estrogen later treatment) and received sham surgery or bilateral ovariectomy and permanent occlusion of bilateral common carotid arteries (BCCAO). The early treatment group received daily intraperitoneal injections of 17β-estradiol (100 µg/kg/day) for 8 weeks starting the day after BCCAO. The later treatment group was administered the same starting 1 week after BCCAO. Learning and memory functions were assessed using the Morris water maze. Morphological changes within the hippocampal CA1 region were observed by hematoxylin/eosin staining and electron microscopy. Expression of proteins associated with autophagy and signaling were detected by immunohistochemical staining and Western blot. We found that estrogen significantly alleviated cognitive damage and neuronal injury and reduced the expression of Beclin1 and LC3B, indicating a suppression of autophagy. Moreover, estrogen enhanced expression of β-catenin and Cyclin D1, while reducing glycogen synthase kinase 3β, suggesting activation of Wnt/β-catenin signaling. These results indicate that estrogen ameliorates learning and memory deficiencies in VD rats, and that this neuroprotective effect may be explained by the suppression of autophagy and activation of Wnt/β-catenin signaling.

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Acknowledgements

This study was supported by the Hebei province High-end Talent Special Subsidy Project and The National Natural Science Foundation of China (Grant No. 81241037).

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Correspondence to Peiyuan Lv.

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The authors declare that they have no conflicts of interest regarding the authorship and publication of this article.

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All experimental procedures and usages corresponded to the regulations for laboratory animal management of the Ministry of Science and Technology of the People’s Republic of China [1988] no. 134. All animal studies were approved by the Animal Care and Use Committee of Hebei General Hospital, Shijiazhuang, China, and performed in accordance with ethical standards.

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Yang, Y., Zhao, L., Li, N. et al. Estrogen Exerts Neuroprotective Effects in Vascular Dementia Rats by Suppressing Autophagy and Activating the Wnt/β-Catenin Signaling Pathway. Neurochem Res 45, 2100–2112 (2020). https://doi.org/10.1007/s11064-020-03072-5

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