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ORIGINAL RESEARCH ARTICLE

Brain-derived neurotrophic factor-overexpressing adipose-derived stem cells attenuate Aβ1–42-induced hippocampal neurodegeneration by suppressing apoptosis

Fangfang Liu1† ,  Aiping Wang2† ,  Xidi Chi1 ,  Guiyun Ye1 ,  Haolin Wu3* ,  Haofei Fan4*
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1 Clinical Laboratory, Nanping First Hospital Affiliated to Fujian Medical University, Nanping, Fujian, China
2 Department of Basic Medicine, Faculty of Basic Medical Sciences, Hainan Vocational University of Science and Technology, Haikou, Hainan, China
3 International Center for Aging and Cancer, Hainan Medical University, Haikou, Hainan, China
4 Equipment Section, Logistics Management Office, School of Basic Medicine and Life Sciences, Hainan Medical University, Haikou, Hainan, China
†These authors contributed equally to this work.
EJMO, 026120137 https://doi.org/10.36922/EJMO026120137
Received: 22 March 2026 | Revised: 5 June 2026 | Accepted: 10 July 2026 | Published online: 14 July 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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Abstract

Introduction: Alzheimer’s disease (AD) manifests as progressive hippocampal neurodegeneration coupled with deteriorating cognitive performance. Although brain-derived neurotrophic factor (BDNF) exerts neuroprotective effects, its translational potential remains constrained.

Objectives: This study evaluated whether BDNF-overexpressing adipose-derived mesenchymal stem cells (BDNF-ADSCs) exert neuroprotective effects in an AD mouse model.

Methods: AD-like hippocampal injury was induced by stereotaxic injection of Aβ1–42 into the CA1 region of mice, followed by local transplantation of BDNF-ADSCs. Behavioral tests assessed anxiety-like behavior and cognitive function. Histological analysis evaluated hippocampal neuronal integrity, and apoptosis-related proteins were examined.

Results: BDNF-ADSC transplantation significantly alleviated anxiety-like behavior and spatial learning and memory impairments induced by Aβ1–42. Histological analyses demonstrated reduced hippocampal neuronal loss and partial restoration of hippocampal cytoarchitecture. Moreover, Aβ1–42 markedly increased Bax expression and caspase-3 activation while decreasing Bcl-2 levels, whereas BDNF-ADSCs reversed these alterations by suppressing pro-apoptotic signaling and enhancing anti-apoptotic protein expression.

Conclusion: BDNF-ADSCs protect against Aβ1–42-induced hippocampal injury and cognitive impairment, partly via modulation of the Bax/Bcl-2/caspase-3 apoptotic pathway, highlighting their potential as a cell-based therapeutic strategy for AD.

Keywords
Alzheimer’s disease
Brain-derived neurotrophic factor
Adipose-derived stem cells
Neuronal apoptosis
Hippocampal neuroprotection
Funding
This research was funded by the Fujian Provincial Natural Science Foundation of China (Grant number: 2023J011869); Nanping Joint Funding Program for Science and Technology Innovation in Healthcare (Grant number: N2024LH006); Startup Fund for scientific research, Fujian Medical University (Grant number: 2022QH1236); Hainan Province for the Scientific Research Projects of Higher Education Institutions in 2023 (Grant number: Hnky2023- 31).
Conflict of interest
The authors declare they have no competing interests.
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Eurasian Journal of Medicine and Oncology, Electronic ISSN: 2587-196X Print ISSN: 2587-2400, Published by AccScience Publishing
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