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Updated: Aug 14, 2026
Chronic Unpredictable Mild Stress in Rats based on the Mongolian medicine
Published on: October 27, 2023
Chronic mild stress disrupts mitophagy and mitochondrial status in rat frontal cortex
Cristina Ulecia-Morón1, Álvaro G Bris1, Karina S MacDowell1
1Departamento de Farmacología y Toxicología, Facultad de Medicina, Universidad Complutense de Madrid (UCM), Centro de Investigación Biomédica en Red de Salud Mental, Instituto de Salud Carlos III (CIBERSAM, ISCIII), Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Instituto Universitario de Investigación Neuroquímica (IUIN-UCM), Plaza Ramón y Cajal s/n, Madrid, 28040, Spain.
Background:
Mitochondria are very dynamic organelles that maintain cellular homeostasis, crucial in the central nervous system. Mitochondrial abnormalities have been described in neuropsychiatric diseases, namely major depression disorder (MDD) and schizophrenia. Since stress is the predominant non-genetic cause of MDD, and has a direct impact on mitochondrial networks, understanding how psychological stress affects mitochondrial health is vital to improve the current pharmacological therapies.
Methods:
The effect of 21 days of unpredictable stress was evaluated in frontal cortex of Wistar male rats comparing protein and gene markers of mitophagy (PINK1, PARKIN, BNIP3, NIX, FUNDC1), mitochondrial biosynthesis (PGC1α, NRF1, TFAM) and dynamics (MFN1, MFN2, OPA1, DRP1), and mitochondrial presence within microglia with the MitoTracker Green FM™ probe.
Results:
Chronic mild stress (CMS) caused the upregulation of mitochondrial mass, mitochondria depolarization, dysregulation in mitochondrial dynamics towards fusion, the increase of mitophagy markers and the induction of genes that activate mitochondrial biogenesis in frontal cortex. CMS also promoted microglia recruitment and mitochondrial number boosting within them.
Conclusions:
There is a dysregulation of mitochondrial dynamics towards fusion, an upregulation of mitophagy markers, and the induction of genes associated with mitochondrial biogenesis in response to CMS in the frontal cortex of adult rats. This study highlights the impact of psychological stress on brain mitochondrial networks.
