BACKGROUND: Parkinson's disease (PD) is characterized by selective degeneration of dopaminergic (DA) neurons of the substantia nigra pars compacta (SN) while neighboring ventral tegmental area (VTA) DA neurons are relatively spared. Mechanisms underlying the selective protection of the VTA and susceptibility of the SN are still mostly unknown. Here, we demonstrate the importance of balance between astrocytes and microglia in the susceptibility of SN DA neurons to the PD mimetic toxin 1-methyl-4-phenylpyridinium (MPP
METHODS: Previously established methods were used to isolate astrocytes and microglia from the cortex (CTX), SN, and VTA, as well as embryonic midbrain DA neurons from the SN and VTA. The transcriptional profile of isolated microglia was examined for 21 canonical pro- and anti-inflammatory cytokines by qRT-PCR with and without MPP
RESULTS: We found that regionally isolated microglia (SN, VTA, CTX) exhibit basal differences in their cytokine profiles and that activation of these microglia with MPP
CONCLUSION: These results suggest that the balance of astrocytes and microglia within the midbrain is a key factor underlying the selective vulnerability of SN DA neurons seen in PD pathogenesis and that VTA astrocytes mediate protection of DA neurons which can be countered by greater numbers of deleterious microglia.
Kostuk, Eric Wildon; Cai, Jingli; and Iacovitti, Lorraine, "Regional microglia are transcriptionally distinct but similarly exacerbate neurodegeneration in a culture model of Parkinson's disease." (2018). Department of Neuroscience Faculty Papers. Paper 35.
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