Systemic energy and neuroinflammatory disturbances in a lactacystin-induced rat model of Parkinson's disease.

Energy and neuroinflammatory disturbances in the blood and brain tissue were studied in a rat model of Parkinson's disease (PD) induced by a double bilateral injection of the ubiquitin-proteasome system (UPS) inhibitor, lactacystin (LC), into the substantia nigra pars compacta (SNpc) of the brain. Experimental modeling of PD was conducted on male Wistar rats (n = 31). The following differences were observed in the LC group 21 days after the start of the experiment: reduced absolute body weight gain and motor activity, as well as spontaneous rotation and compulsive-like behavior in the open field test. The LC model of PD showed a more than twofold reduction in tyrosine hydroxylase (TH) expression in the SNpc, hypertrophy of IBA1-positive microglial cells, and increased GFAP expression. Cytokine activity in the brain mitochondria and serum of animals with LC was characterized by systemic inflammation: elevated levels of IL-6 and TNF-α and increased production of the anti-inflammatory cytokine IL-10. Activation of the pro-inflammatory signaling pathway NF-κB was observed in the striatum, while in the SNpc, its activity was reduced. Analysis of mitochondria isolated from the brains of LC rats revealed an increase in the rate of hydrogen peroxide production and potassium levels, as well as a decrease in the rate of potassium ion transport in brain mitochondria. We were the first to demonstrate that rats with PD symptoms induced by LC had impaired energy metabolism in blood lymphocytes (hyperactivation of succinate and lactate dehydrogenase) and increased serum lipid peroxidation, which may serve as biomarkers of systemic inflammation and oxidative stress.