Impact of Restraint Stress on Mitochondrial Ion Transporter Activity in Mice Brain-Gut Regions and Gender Response to Aging

The ability to respond suitably and maintain a steady state after exposure to stressors is an essential dynamic element in maintaining ion homeostasis. Besides the factors linked to the stressor itself, there are aspects intrinsic to the organisms that are pertinent to shape the stress response, such as age, gender and genetics. This study in mice analyses the functional role of mitochondria, which may affect the integrated responses to psychological stress. Mitochondria depend on a series of ion transporters to interface the communication between the cytosol and the site of energy production, which is key to the survival of the organism. Ion transporters, like mCa²⁺ATPase, F₁F₀ATPase and mH⁺ATPase, are the functional components of the mitochondria involved in Ca²⁺, H⁺ homeostasis and energy production. Since the process of aging starts with the birth, and ends with the death of an organism, physiological and molecular processes tend to vary throughout aging. Moreover, males and females have qualitatively different mitochondria, and only a little is known about the mitochondrial responses to stressors. Therefore, we hypothesized that mitochondrial ion transporter functions would modulate the organism’s multisystemic response to psychological stress in an age-, gender- and tissue-specific manner. In this study, BALB/c mice of different age groups (4 weeks-, 8 weeks-, 16 weeks- and 24 weeks-old mice) were subjected to restraint stress of 30 minutes for two consecutive days and the ion transporter activity was quantified in the different regions of the brain (cerebrum, cerebellum and hippocampus) and the gut (duodenum of the intestine, fundus and pyloric regions of the stomach). Overall, the data indicate that in mice both gender-specific and age-specific differential sensitivities to restraint stress exist in mitochondrial ion transporter function in the brain and gut regions. This further points to a decisive interactive role of stress and sex hormones in the energetics and ion transport performance of brain-gut axis in mice.