Host: The Japanese Society of Toxicology
Name : The 51st Annual Meeting of the Japanese Society of Toxicology
Date : July 03, 2024 - July 05, 2024
Parkinson’s disease (PD) is a progressive neurodegenerative disease with motor symptoms due to a loss of nigrostriatal dopaminergic neurons, and non-motor symptoms which precedes motor symptoms. Pathologically, neurodegeneration accompanied by α-synuclein accumulation is thought to propagate from the peripheral enteric nervous system or within the brain, and exhibit motor symptoms when it reaches the substantia nigra. However, the mechanism of neurodegeneration in PD is still unknown. Currently, prion-like cell-to-cell propagation of α-synuclein aggregation is a plausible hypothesis on neuropathology. Glial cells play pivotal role in not only maintenance of neuronal environment by energy supply and immune defense but also degradation of α-synuclein aggregation. On the other hand, glial cells promote neuroinflammation followed by neurotoxicity in the pathological condition. We have demonstrated that exposure to the pesticide rotenone, an environmental risk factor in PD, induced brain region-specific glial dysfunction mediated by astrocyte-microglia interactions, and caused non-cell autonomous dopaminergic neurodegeneration. Furthermore, we found that glial cells secrete protective molecules which inhibit or degrade protein aggregation, and that rotenone reduced their secretions. In this symposium, we will outline the above findings and also introduce our recent examination that involvement of glial cells in neurotoxicity induced by α-synuclein aggregation in the central and peripheral enteric nervous system.
