Study of Metabolic Plasticity of the Brain in Animals with Modeled Parkinson’s Disease

Abstract

Neuroinflammation plays the key role in progression of Parkinson’s disease (PD), the neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons of the substantia nigra, which results in the motor impairment. The major pathogenetic mechanisms of PD are metabolic dysfunctions, mitochondrial impairments and inflammatory response determined by the activation of microglia. Understanding the molecular pathways underlying these processes is an important stage in the development of target therapeutic strategies. Recent studies have emphasized the significance of lactate metabolism and the related signaling pathways in modulation of both neuroinflammation and energy homeostasis. GPR81, also known as HCAR1, is a lactate receptor involved in the regulation of metabolism and inflammatory processes. In spite of the well-studied role of this receptor in peripheral tissues, its involvement in the pathogenesis of neurodegenerative diseases such as PD yet remains insufficiently studied. In the present study, the expression of GPR81 in the substantia nigra of the rat brain is studied under the conditions of LPS-induced PD model with the accent on its potential role in the regulation of inflammatory and metabolic processes. The analysis of dynamic changes in the expression of GPR81 will reveal its contribution to neuroprotection and metabolic plasticity of the brain, opening up new prospects for slowing down neurodegeneration in PD.