Original Articles
Vol. 9 No. 1 (2025)
Structural and ultrastructural organization of the parietal cortex and dorsal hippocampus in transgenic 5xFAD mice administered sodium valproate, a histone deacetylase inhibitor
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Published: 24 December 2025
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Light and electron microscopy revealed significant neuropathological alterations in both parietal cortical and hippocampal tissues of 7-month-old 5xFAD (familial Alzheimer’s disease) transgenic mice, a well-established model of human Alzheimer’s disease (AD), compared to age-matched wild-type controls. Key pathological findings included neuronal degeneration, extensive β- amyloid (Aβ) plaque deposition in the neuropil, and astroglial activation with elevated glial fibrillary acidic protein (GFAP) expression in affected brain regions. Consistent with AD-like pathology, 5xFAD mice exhibited cognitive deficits resembling human dementia, which correlated with reduced activity of neprilysin (NEP), the principal amyloid-degrading enzyme. To counteract the reduction in NEP level, we performed daily intraperitoneal administration of the histone deacetylase (HDAC) inhibitor sodium valproate (VA; 200 mg/kg body weight) for one month. VA treatment of adult mice normalized NEP expression levels, restored olfactory and mental functions, and significantly reduced amyloidosis progression. Notably, while VA treatment ameliorated major pathological features, residual ultrastructural abnormalities persisted in cortical and hippocampal tissues. These findings highlight the critical role of amyloid clearance mechanisms in early AD pathogenesis. It can be concluded that the therapeutic potential of NEP upregulation might be crucial as an early therapy strategy applied prior to extensive Aβ plaque formation and irreversible neurodegeneration.
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How to Cite
Structural and ultrastructural organization of the parietal cortex and dorsal hippocampus in transgenic 5xFAD mice administered sodium valproate, a histone deacetylase inhibitor. (2025). Veterinary Science Development, 9(1). https://doi.org/10.4081/vsd.2025.10639
Copyright (c) 2025 Natalia L. Tumanova, Dmitrii S. Vasilev, Nadezhda M. Dubrovskaya, Natalia N. Nalivaeva
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.