Regional microglia are transcriptionally distinct but similarly exacerbate neurodegeneration in a culture model of Parkinson's disease

Journal of Neuroinflammation
Eric W KostukLorraine Iacovitti

Abstract

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+). 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+ exposure. Homo- and heterotypic co-cultures of neurons and astrocytes were established, and the effect of altering the ratio of astrocytes and microglia in vitro on the susceptibility of midbrain DA neurons to the PD mimetic toxin MPP+ was investigated. We found that regionally isolated microglia (SN, VTA, CTX) exhibit basal differences in their cytokine profiles and that activation of these microglia with...Continue Reading

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Citations

Mar 19, 2019·Anesthesia and Analgesia·Saraswathi Subramaniyan, Niccolò Terrando
May 7, 2021·Frontiers in Immunology·Andrea ManciniMassimiliano Di Filippo

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Methods Mentioned

BETA
dissection
enzymatic dissociation
mechanical dissociation
PCR
transgenic
RNAseq

Key Resources (RRID) Mentioned

AB_2665520
AB_393594

Software Mentioned

ImageJ

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