Psychological Stress Phenocopies Brain Mitochondrial Dysfunction and Motor Deficits as Observed in a Parkinsonian Rat Model

AbstractPsychological distress is a public health issue as it contributes to the development of human diseases including neuropathologies. Parkinson ’s disease (PD), a chronic, progressive neurodegenerative disorder, is caused by multiple factors including aging, mitochondrial dysfunction, and/or stressors. In PD, a substantial loss ofsubstantia nigra (SN) neurons leads to rigid tremors, bradykinesia, and chronic fatigue. Several studies have reported that the hypothalamic-pituitary-adrenal (HPA) axis is altered in PD patients, leading to an increase level of cortisol which contributes to neurodegeneration and oxidative stress. We hypothesized that chronic psychological distress induces PD-like symptoms and promotes neurodegeneration in wild-type (WT) rats and exacerbates PD pathology in PINK1 knockout (KO) rats, a well-validated animal model of PD. We measured the bioenergetics profile (oxidative phosphorylation and glycolysis) in the brain by employing an XF24e Seahorse Extracellular Flux Analyzer in young rats subjected to predator-induced psychological distress. In addition, we analyzed anxiety-like behavior, motor function, expression of antioxidant enzymes, mitochondrial content, and neurotrophic factors brain-derived neurotrophic factor (BDNF) in the brain. Overall, we observed that psychological distress diminished up to 50% of mitochondrial respiration and glycolysis in the prefrontal cortex (PFC) derived from both WT and PINK1-KO rats. Mechanistically, the level o...
Source: Molecular Neurobiology - Category: Neurology Source Type: research