Glucocorticoid receptor in astrocytes regulates midbrain dopamine neurodegeneration through connexin hemichannel activity

Cell Death and Differentiation
Layal MaatoukSheela Vyas

Abstract

The precise contribution of astrocytes in neuroinflammatory process occurring in Parkinson's disease (PD) is not well characterized. In this study, using GRCx30CreERT2 mice that are conditionally inactivated for glucocorticoid receptor (GR) in astrocytes, we have examined the actions of astrocytic GR during dopamine neuron (DN) degeneration triggered by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The results show significantly augmented DN loss in GRCx30CreERT2 mutant mice in substantia nigra (SN) compared to controls. Hypertrophy of microglia but not of astrocytes was greatly enhanced in SN of these astrocytic GR mutants intoxicated with MPTP, indicating heightened microglial reactivity compared to similarly-treated control mice. In the SN of GR astrocyte mutants, specific inflammation-associated transcripts ICAM-1, TNF-α and Il-1β as well as TNF-α protein levels were significantly elevated after MPTP neurotoxicity compared to controls. Interestingly, this paralleled increased connexin hemichannel activity and elevated intracellular calcium levels in astrocytes examined in acute midbrain slices from control and mutant mice treated with MPP+ . The increased connexin-43 hemichannel activity was found in v...Continue Reading

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Citations

Oct 23, 2019·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Mohd Nasir Mat NorMonica L Acosta
Aug 23, 2020·International Journal of Molecular Sciences·Peter Illes
Aug 28, 2019·Journal of Experimental Neuroscience·Gianfilippo CoppolaNatalina Salmaso
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Jan 4, 2021·Cellular and Molecular Life Sciences : CMLS·Raghda RamadanLuc Leybaert
Jan 12, 2021·Frontiers in Oncology·Kai-Jun LuoJean X Jiang
Feb 16, 2021·Neurochemistry International·Katherine PicardMarie-Ève Tremblay
Feb 21, 2021·Neurobiology of Disease·Gee Euhn Choi, Ho Jae Han
Jun 15, 2021·Frontiers in Molecular Neuroscience·Xiaomin HuangChenju Yi
Dec 24, 2021·Journal of Neuroendocrinology·Eva M G VihoOnno C Meijer

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Methods Mentioned

BETA
ELISA
PCR
biopsies
protein assay

Software Mentioned

ImageJ
Mercator
Explora Nova VisioScan
MCID TM Analysis system
StatView
ARIVIS

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