Early Handling Exerts Anxiolytic Effects and Alters Brain Mitochondrial Dynamics in Adult High Anxiety Mice.

Autor: Thomou C; Laboratory of Biochemistry, Department of Biological Applications and Technology, University of Ioannina, Ioannina, Greece.; Biomedical Research Institute, Foundation for Research and Technology-Hellas (FORTH), Ioannina, Greece., Nussbaumer M; Laboratory of Biochemistry, Department of Biological Applications and Technology, University of Ioannina, Ioannina, Greece.; Biomedical Research Institute, Foundation for Research and Technology-Hellas (FORTH), Ioannina, Greece., Grammenou E; Laboratory of Biochemistry, Department of Biological Applications and Technology, University of Ioannina, Ioannina, Greece.; Biomedical Research Institute, Foundation for Research and Technology-Hellas (FORTH), Ioannina, Greece., Komini C; Laboratory of Biochemistry, Department of Biological Applications and Technology, University of Ioannina, Ioannina, Greece.; Biomedical Research Institute, Foundation for Research and Technology-Hellas (FORTH), Ioannina, Greece., Vlaikou AM; Laboratory of Biochemistry, Department of Biological Applications and Technology, University of Ioannina, Ioannina, Greece.; Biomedical Research Institute, Foundation for Research and Technology-Hellas (FORTH), Ioannina, Greece., Papageorgiou MP; Laboratory of Biochemistry, Department of Biological Applications and Technology, University of Ioannina, Ioannina, Greece.; Biomedical Research Institute, Foundation for Research and Technology-Hellas (FORTH), Ioannina, Greece., Filiou MD; Laboratory of Biochemistry, Department of Biological Applications and Technology, University of Ioannina, Ioannina, Greece. mfiliou@uoi.gr.; Biomedical Research Institute, Foundation for Research and Technology-Hellas (FORTH), Ioannina, Greece. mfiliou@uoi.gr.; Institute of Biosciences, University of Ioannina, Ioannina, Greece. mfiliou@uoi.gr.
Jazyk: angličtina
Zdroj: Molecular neurobiology [Mol Neurobiol] 2024 Dec; Vol. 61 (12), pp. 10593-10612. Date of Electronic Publication: 2024 May 18.
DOI: 10.1007/s12035-024-04116-5
Abstrakt: Early handling (EH), the brief separation of pups from their mother during early life, has been shown to exert beneficial effects. However, the impact of EH in a high anxiety background as well as the role of brain mitochondria in shaping EH-driven responses remain elusive.Here, we used a high (HAB) vs. normal (NAB) anxiety-related behavior mouse model to study how EH affects pup and dam behavior in divergent anxiety backgrounds. We also investigated EH-induced effects at the protein and mRNA levels in adult male HAB mice in the hypothalamus, the prefrontal cortex, and the hippocampus by examining the same mitochondrial/energy pathways and mitochondrial dynamics mechanisms (fission, fusion, biogenesis, and mitophagy) in all three brain regions.EH exerts anxiolytic effects in adult HAB but not NAB male mice and does not affect HAB or NAB maternal behavior, although basal HAB vs. NAB maternal behaviors differ. In adult HAB male mice, EH does not impact oxidative phosphorylation (OXPHOS) and oxidative stress in any of the brain regions studied but leads to increased protein expression of glycolysis enzymes and a correlation of anxiety-related behavior with Krebs cycle enzymes in HAB mice in the hypothalamus. Intriguingly, EH alters mitochondrial dynamics by increasing hypothalamic DRP1, OPA1, and PGC1a protein levels. At the mRNA level, we observe altered, EH-driven mitochondrial dynamics mRNA signatures which predominantly affect the prefrontal cortex.Taken together, our results show that EH exerts anxiolytic effects in adulthood in high anxiety and modulates mitochondrial dynamics pathways in a brain region-specific manner.
Competing Interests: Declarations. Ethics Approval: Animal work was carried out in accordance with the European Communities Council Directives 2010/63/EU and approved by the local authorities. Consent to Participate: Not applicable. Consent for Publication: Not applicable. Competing Interests: The authors declare no competing interests.
(© 2024. The Author(s).)
Databáze: MEDLINE
Externí odkaz: