ORIGINAL RESEARCH article
Front. Aging Neurosci.
Sec. Alzheimer's Disease and Related Dementias
Dexmedetomidine Ameliorates Cognitive and Affective Deficits by Modulating Neuroinflammation and Neurogenesis in an Alzheimer's Disease Mouse Model
Provisionally accepted
Mai Li1Chanyuan An2Xin Wang2
Minghe Ren2Shiyu Liu2Ruixin Chen2
Yuyan Guo3Jun Wang4Yulang Fei5Dafei Ma6
Kaige Ma2
Yuming Zhang1*- 1Shaanxi Provincial People's Hospital, Xi'An, China
- 2School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi'an, China
- 3Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
- 4Shaanxi Provincial Cancer Hospital, Xi'an, China
- 5The First Affiliated Hospital of Nanyang Medical College, Nanyang, China
- 6Golden horse Arts & Grafts Co..Ltd, Zhejiang, China
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Alzheimer’s disease (AD) involves progressive cognitive decline and neuropsychiatric symptoms that are strongly linked to neuroinflammation and aberrant hippocampal neurogenesis. We examined whether dexmedetomidine (Dex), a clinically used selective α2-adrenergic agonist, could mitigate Aβ1-42–induced pathology in mice. After intracerebroventricular Aβ1-42 injection, animals were treated with Dex (25 or 50 μg/kg/day) for seven days; a subgroup additionally received the α2 antagonist Yohimbine. Behavioral tests showed improved memory performance across recognition and spatial paradigms, accompanied by reduced anxiety-like behavior in exploratory assays. Histological analyses with Nissl and doublecortin (DCX) staining indicated preserved neuronal integrity, fewer degenerating cells, and normalization of pathological neurogenesis. At the molecular level, Dex suppressed the expression of pro-inflammatory and apoptotic genes (CXCL2, IL-1β, iNOS, SPHK1) and lowered hippocampal malondialdehyde, consistent with reduced oxidative stress and improved cellular resilience. Yohimbine partly reversed these effects, supporting α2-adrenergic involvement but leaving open the possibility of additional pathways contributing to the response. Overall, our results suggest that Dex protects against Aβ-driven injury through coordinated regulation of neuroinflammation, oxidative stress, and neurogenesis, underscoring its promise as a molecularly targeted candidate for early therapeutic strategies in AD management.
Keywords: Alzheimer's disease, Dexmedetomidine, Neuroinflammation, Neurogenesis, Cognition
Received: 14 Oct 2025; Accepted: 02 Dec 2025.
Copyright: © 2025 Li, An, Wang, Ren, Liu, Chen, Guo, Wang, Fei, Ma, Ma and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yuming Zhang
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