Psychophysical stress disturbs expression of mitochondrial biogenesis markers in hypothalamus and adenohypophysis

Abstract

Summary. Although psychophysical stress is widespread in human society and a major contributor to a range of pathological conditions, it is not known if this form of stress regulates mitochondrial biogenesis in the hypothalamus or adenohypophysis, the main organs involved in compensatory specifc response of the organism to stress (so called “fght or flight” response). Accordingly, this study was designed to evaluate the effects of acute and repeated psychophysical stress on a profle of mitochondrial biogenesis markers in the hypothalamus and adenohypophysis. Rats were either lef undisturbed (freely moving, control group) or exposed to psychophysical stress by immobilization (IMO) for 2 h (acute, 1xIMO) or 2 h daily for 2 (repeated, 2xIMO) or 10 consecutive days (repeated, 10xIMO).Result suggest that all types of immobilization stress signifcantly increase expression of hypothalamic NRF1 (nuclear respiratory factor 1; acts on the genes for subunits of the OXPHOS encoded by the nuclear genome) as well as its downstream target TFAM (mitochondrial transcription factor A), the essential ubiquitous factors for mtDNA replication and expression. In the same samples, TFB1M (markedly enhance mtDNA transcription) significantly decreased, while the level of COX4 (mitochondrial complex IV cytochrome C oxidase) protein was reduced only in hypothalamuses isolated from repeatedly stressed rats. Independently of the type of stress, the level of PGC1 protein, the master regulator of mitochondrial biogenesis involved in transcriptional control of all processes related to mitochondrial homeostasis and integrator of environmental signals, remained unchanged. In adenohypophyses of the same animals, 10xIMO signifcantly increased expression of adenohypophyseal PGC1 as well as its downstream target TFB1M, while NRF1 and TFAM remained unchanged. Similarly to hypothalamuses, the level of COX4 protein was reduced in adenohypophyses isolated from repeatedly stressed rats. Our results provide new molecular insights into the relationship between stress and hypothalamo-adenohypophyseal axis, as well as mitochondrial biology.