Compartment-Specific Mitochondrial Proteomic Alterations in Rat Hippocampus Following Chronic Social Isolation Stress

Dragana Filipović

doi:10.3390/ijms27083386

journal article Open Access Apr 09, 2026

Compartment-Specific Mitochondrial Proteomic Alterations in Rat Hippocampus Following Chronic Social Isolation Stress

Dragana Filipović

International Journal of Molecular Sciences Vol. 27 No. 8 pp. 3386 · MDPI AG

View at Publisher Save 10.3390/ijms27083386

Abstract

Chronic social isolation (CSIS) is a form of psychosocial stressor strongly associated with the development of depression. Preclinical studies demonstrated that CSIS induces behavioral phenotypes resembling human depression, including anhedonia, behavioral despair and anxiety. This review summarizes proteomic-driven discoveries characterizing hippocampal non-synaptic mitochondria (NSM) and synaptosomal fractions containing synaptic mitochondria from adult male rats exposed to six weeks of CSIS, an animal model of depression, compared to controls. The compartment-specific proteomic alterations reveal mechanisms underlying mitochondrial dysregulation, providing molecular insights into the depression-like phenotype. Hippocampal NSM exhibit changes in energy metabolism-related proteins, including components of the tricarboxylic acid cycle and oxidative phosphorylation, as well as mitochondrial transport proteins and alterations in chaperones, structural and translational proteins, and monoamine oxidase, further elucidating how these proteomic changes contribute to mitochondrial dysregulation. In contrast, synaptosomal proteomics reveal predominantly increased protein abundance associated with energy metabolism, signaling, cytoskeletal organization, protein quality control, and vesicle trafficking, suggesting compensatory adaptations. Together, these findings highlight compartment-specific mitochondrial proteomic changes that may underlie depression-like behaviors and represent potential targets for therapeutic intervention.

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Published: Apr 09, 2026
Vol/Issue: 27(8)
Pages: 3386
License: View

Authors

D

Dragana Filipović

Department of Molecular Biology and Endocrinology, “VINČA”, Institute of Nuclear Sciences—National Institute of the Republic of Serbia, University of Belgrade, 11000 Belgrade, Serbia

Funding

Ministry of Education, Science and Technological Development of the Republic of Serbia Award: 451-03-136/2025-03/ 200017

Cite This Article

Dragana Filipović (2026). Compartment-Specific Mitochondrial Proteomic Alterations in Rat Hippocampus Following Chronic Social Isolation Stress. International Journal of Molecular Sciences, 27(8), 3386. https://doi.org/10.3390/ijms27083386

Compartment-Specific Mitochondrial Proteomic Alterations in Rat Hippocampus Following Chronic Social Isolation Stress

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