| First Author | Li H | Year | 2020 |
| Journal | Biochim Biophys Acta Mol Basis Dis | Volume | 1866 |
| Issue | 1 | Pages | 165590 |
| PubMed ID | 31706914 | Mgi Jnum | J:282301 |
| Mgi Id | MGI:6378645 | Doi | 10.1016/j.bbadis.2019.165590 |
| Citation | Li H, et al. (2020) The deficiency of NRSF/REST enhances the pro-inflammatory function of astrocytes in a model of Parkinson's disease. Biochim Biophys Acta Mol Basis Dis 1866(1):165590 |
| abstractText | Neuroinflammation, as an important pathological characteristic of Parkinson's disease (PD), is primarily mediated by activated astrocytes and microglia. Neuron-restrictive silencer factor/repressor element 1 (RE1)-silencing transcription factor (NRSF/REST) regulates many genes and signal pathways involved in the inflammatory process in astrocytes. In the present study, we established the GFAP-Cre:NRSF(flox/flox) conditional knockout (cKO) mice. The expression of inflammation-associated molecules were measured in primary astrocytes from wild type (WT) and cKO mice after stimulation by 1-Methyl-4-phenylpyridine (MPP(+)), LPS, and conditioned medium (CM) of LPS-treated BV-2 microglial cells. The inflammatory molecule expression in BV-2 microglial cells exposed to conditioned medium of MPP(+)-treated primary astrocytes were also analyzed. Moreover, a subacute regimen of 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine hydrochloride (MPTP) was used to establish mouse PD model and the damages to the nigrostriatal pathway were comprehensively evaluated in WT and cKO mice. We found that MPP(+) induced a remarkable increase of NRSF expression in cultured astrocytes. Compared to WT astrocytes, the expression of inflammatory molecules IL-1beta, IL-6, COX-2, and iNOS increased dramatically in NRSF deficient astrocytes challenged with CM of LPS-treated BV-2 cells. COX-2 and IL-1beta transcripts were significantly elevated in BV-2 microglial cells exposed to CM of MPP(+)-treated NRSF deficient astrocytes compared to WT astrocytes. In cKO mice, the activation of astrocytes and microglial cells was more obvious, and the nigrostriatal dopaminergic system was more heavily injured compared to their WT counterparts after MPTP administration. Our results suggest that reactive NRSF deficient astrocytes orchestrated with microglial cells aggravate the pathophysiological progress in PD. |
