Host: The Japanese Society of Toxicology
Name : The 50th Annual Meeting of the Japanese Society of Toxicology
Date : June 19, 2023 - June 21, 2023
Parkinson’s disease (PD) is a progressive neurodegenerative disease with motor symptoms, such as akinesia/bradykinesia, tremor, rigidity, and postural instability, due to a loss of nigrostriatal dopaminergic neurons. Although various pathogenic factors, such as oxidative stress, neuroinflammation, mitochondrial impairment and α-synuclein toxicity, are indicated, the mechanism of neurodegeneration in PD remains unknown. Glial cells play pivotal role in maintenance of neuronal environment in the central nervous system by energy supply and immune defense; however, glial cells promote neuroinflammation followed by neurotoxicity. Recently, it is reported that activated microglia convert astrocytes to neurotoxic A1phenotype. Thus, contribution of astrocyte-microglia crosstalk has been received attention. Furthermore, glial cells exhibit not only morphological but also functional diversity depending on brain region. 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 secreted molecules from microglia, which were treated with conditioned media from rotenone-treated astrocytes, induced dopaminergic neuronal death. In this symposium, we will outline recent findings on astrocyte-microglia crosstalk in PD pathology and would like to discuss the investigation on the mechanism of PD pathogenesis focusing on the regional specificity of glial cells.
