Region-specific nitric oxide production in cytosolic and mitochondrial compartments of the rat brain tissues following chronic stress-induced depression-like behavior

Abstract

Aim. To study subcellular nitrergic response in the rat brain regions following chronic stress-induced depression-like behavior. Methods. An animal model of depression induced by chronic circadian stress (CCS) established in our laboratory was used. The L-arginine, L-citrulline and reactive nitrogen species (RNS) levels were determined spectrophotometrically. Results. Immediately after CCS and four days later, a depression-like behavior of rats was observed and accompanied by a substantial persistent elevation of the L-arginine, L-citrulline and RNS levels with a simultaneous up-regulation of the inducible nitric oxide synthase (iNOS) in both cytosolic and mitochondrial compartments of the rat prefrontal cortex, striatum, hippocampus, and hypothalamus, and a down-regulation of their cytosolic constitutive NOS isoforms (cNOS), mitochondrial cNOS was not significantly changed, with the exception for hypothalamus, in which the latter dropped. Conclusions. Compromised balance of the L-arginine levels and NO synthesis in both mitochondria and cytosol in the limbic brain appears to be implicated in the pathogenesis of depression and pathological anxiety

Targeted placental deletion of OGT recapitulates the prenatal stress phenotype including hypothalamic mitochondrial dysfunction

“…Results confirmed that in both EPS and Pl-OGT mice, hypothalamic mitochondria function was significantly reduced, linking placental OGT again to EPS brain programming. Hypothalamic mitochondrial dysfunction has previously been associated with altered whole-body growth and energy homeostasis, as well as stress-related depressive-like behaviors (33)(34)(35)(36)(37)(38). Therefore, the observed phenotypes in male EPS and Pl-OGT mice (HPA hyperresponsivity and dysregulated energy homeostasis) appear to be, at least in part, the result of mitochondrial dysfunction programmed by a reduction in placental OGT during gestation.…”