Journal of Endocrinology and Reproduction

Ajith M. Thomas ¹, Lija L. Raju ¹, K. Manish ², M. C. Subhash Peter ¹

Affiliations
1 Department of Zoology, University of Kerala, Kariavattom, Thiruvananthapuram – 695581, Kerala, IN
2 Inter-University Centre for Evolutionary and Integrative Biology iCEIB, University of Kerala, Kariavattom, Thiruvananthapuram – 695581, Kerala, IN

Abstract

Ageing is believed to be a continuous process that begins at conception and proceeds until death. Little is known about the response of mice to ageing and restraint stress. Therefore, in this study, BALB/c mice of different age groups (1, 2, 4 and 6 months) were subjected to restraint stress of 30 min for two consecutive days. Ion transporters being the ion homeostasis regulators of the cell, we explored the response of Na+/K+-ATPase (NKA) and Plasma Membrane Calcium ATPase (PMCA) to restraint stress, an acute stressor. We examined the activity pattern of these ATPases in mice gut (fundus and pyloric regions of the stomach, the duodenum and the jejunum) and brain (cortex, hippocampus and cerebellum) in the stressed condition. The pattern of NKA and PMCA activities showed significant shift in stressed mice that corresponds with increasing age. This differential pattern of ion transporter response in the varied regions of the brain and gut present physiological evidence for a spatio-temporal modification of ion-transporter activity during ageing and restraint stress. Overall, the present data point to a vital role of brain-gut axis in the regulation of ion homeostasis in male mice.

Keywords

Ageing, Brain-Gut Axis, Na⁺/K⁺ATPase, Mice, PMCA, Restraint Stress.

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S. Simi ¹, K. Manish ², M. C. Subhash Peter ¹

Affiliations
1 Department of Zoology, School of Life Sciences, University of Kerala, Kariavattom, Thiruvananthapuram – 695 581, Kerala, IN
2 Inter-University Centre for Evolutionary and Integrative Biology (iCEIB), School of Life Sciences, University of Kerala, Kariavattom, Thiruvananthapuram – 695 581, Kerala, IN

Abstract

Thyroid hormones (TH) have a multitude of actions, mainly on development and differentiation during early life and play many vital roles in almost all tissues including neuronal tissues. TH rapidly alters the mitochondrial functions both by its genomic and direct actions on mitochondrial binding sites. The functional relationship between TH and mitochondrial ion transport during stress response has not yet been elucidated in mammals so far. Here, we report a rapid in vivo action of triiodothyronine (T₃) on mitochondrial ion transporter functions in the neuronal clusters of cortex, hippocampus and cerebellum of Swiss Albino mouse (Mus musculus) treated short-term with triiodothyronine (T₃; 200ng g^-1) for 30 min either in non-stressed or in restraint-stressed (30 min each day for 7 days). The mH⁺-ATPase activity in the cortex decreased to significant levels after T₃ treatment in both non-stressed and restraint-stressed mice. On the contrary, the mH⁺-ATPase activity in the hippocampus and cerebellum increased to significant levels after T₃ treatment in both non-stressed and restraint-stressed mice. The mCa²⁺-ATPase activity in the cortex and cerebellum decreased to significant levels after T₃ treatment in both non-stressed and restraint-stressed mice. The mCa²⁺-ATPase activity in the hippocampus that increased to significant levels after T₃ treatment, showed a reversal after restraint-stress in T₃-treated mice. The mitochondrial Mg²⁺-ATPase activity in the cortex decreased to significant levels after T₃ treatment in restraint-stressed mice. On the contrary, T₃ treatment in restraint stressed mice increased to significant levels the mitochondrial Mg²⁺-ATPase activity in the cerebellum. The mitochondrial Mg²⁺-ATPase activity in the hippocampus, which increased to significant levels after T₃ treatment in non-stressed mice, reversed its activity in T₃-treated restraint-stressed mice. Spatial and differential action of T₃ on the mitochondrial ion transporters has been found in the present study that corroborates with a rapid modulatory action of T₃ on the transport of H⁺, Ca²⁺ and Mg²⁺ in the brain mitochondria of mice which appears to be sensitive to restraint stress.

Keywords

Brain, Mice, Mitochondrial Ca²⁺, H⁺, Mg²⁺ATPase, Restraint Stress, Triiodothyronine.

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Lija L. Raju ¹, Ajith M. Thomas ², K. Manish ², Valsa S. Peter ², M. C. Subhash Peter ¹

Affiliations
1 Department of Zoology, Inter-University Centre for Evolutionary and Integrative Biology iCEIB, School of Life Sciences, University of Kerala, Kariavattom, Thiruvananthapuram - 695581, Kerala, IN
2 Inter-University Centre for Evolutionary and Integrative Biology iCEIB, School of Life Sciences, University of Kerala, Kariavattom, Thiruvananthapuram - 695581, Kerala, IN

Abstract

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.

Keywords

Aging, Brain Gut Axis, Ion Transport, Mice, Mitochondria, Restraint Stress

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