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. 2025 Feb;62(2):1337-1358.
doi: 10.1007/s12035-024-04346-7. Epub 2024 Jul 9.

A Mouse Model of Sporadic Alzheimer's Disease with Elements of Major Depression

N V Bobkova #  1 , L N Chuvakova #  2 , V I Kovalev  1 , D Y Zhdanova  1 , A V Chaplygina  1 , A P Rezvykh  2 , M B Evgen'ev  3
Affiliations

A Mouse Model of Sporadic Alzheimer's Disease with Elements of Major Depression

N V Bobkova et al. Mol Neurobiol. 2025 Feb.

Abstract

After olfactory bulbectomy, animals are often used as a model of major depression or sporadic Alzheimer's disease and, hence, the status of this model is still disputable. To elucidate the nature of alterations in the expression of the genome after the operation, we analyzed transcriptomes of the cortex, hippocampus, and cerebellum of the olfactory bulbectomized (OBX) mice. Analysis of the functional significance of genes in the brain of OBX mice indicates that the balance of the GABA/glutamatergic systems is disturbed with hyperactivation of the latter in the hippocampus, leading to the development of excitotoxicity and induction of apoptosis in the background of severe mitochondrial dysfunction and astrogliosis. On top of this, the synthesis of neurotrophic factors decreases leading to the disruption of the cytoskeleton of neurons, an increase in the level of intracellular calcium, and the activation of tau protein hyperphosphorylation. Moreover, the acetylcholinergic system is deficient in the background of the hyperactivation of acetylcholinesterase. Importantly, the activity of the dopaminergic, endorphin, and opiate systems in OBX mice decreases, leading to hormonal dysfunction. On the other hand, genes responsible for the regulation of circadian rhythms, cell migration, and innate immunity are activated in OBX animals. All this takes place in the background of a drastic downregulation of ribosomal protein genes in the brain. The obtained results indicate that OBX mice represent a model of Alzheimer's disease with elements of major depression.

Keywords: Alzheimer’s disease; Depression; Olfactory bulbectomized mice; Transcriptomic analysis.

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Conflict of interest statement

Declarations. Ethics Approval: All animal experiments were conducted in agreement with the Provision and General Recommendation of Chinese Experimental Animals Administration Legislation and were approved by the Animal Ethics Committee in the Institute (SLXD-20180912006, 12 September 2018) in compliance with Russian Federation legislation. Consent to Participate: Informed consent was obtained from all individual participants and authors involved in the study. Consent for Publication: We confirm that consent to publish has been received from all participants involved in this study. Competing Interests: The authors declare no competing interests.

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