Transcriptomics

Dataset Information

0

A Molecular Switch for Neuroprotective Astrocyte Reactivity


ABSTRACT: The intrinsic mechanisms that regulate neurotoxic versus neuroprotective astrocyte phenotypes and their effects on central nervous system (CNS) degeneration and repair remain poorly understood. Here, we show injured white matter astrocytes differentiate into two distinct C3-positive and C3-negative reactive populations, previously simplified as neurotoxic (A1) and neuroprotective (A2)1,2, which can be further subdivided into unique subpopulations defined by proliferation and differential gene expression signatures. We find the balance of neurotoxic versus neuroprotective astrocytes is regulated by discrete pools of compartmented cAMP derived from soluble adenylyl cyclase (sAC) and show proliferating neuroprotective astrocytes inhibit microglial activation and downstream neurotoxic astrocyte differentiation to promote retinal ganglion cell (RGC) survival. Finally, we report a new, therapeutically tractable viral vector to specifically target optic nerve head astrocytes and show elevating nuclear or depleting cytoplasmic cAMP in reactive astrocytes inhibits deleterious immune cell infiltration and promotes RGC survival after optic nerve injury. Thus, soluble adenylyl cyclase and compartmented, nuclear- and cytoplasmic-localized cAMP in reactive astrocytes act as a molecular switch for neuroprotective astrocyte reactivity that can be targeted to inhibit microglial activation and neurotoxic astrocyte differentiation to therapeutic effect. These data expand upon and define new reactive astrocyte subtypes and represents a novel step towards the development of gliotherapeutics for the treatment of glaucoma and other optic neuropathies.

ORGANISM(S): Homo sapiens

PROVIDER: GSE245816 | GEO | 2023/12/11

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2023-12-11 | GSE237675 | GEO
2024-04-10 | GSE241131 | GEO
2024-08-31 | GSE241192 | GEO
2024-08-28 | GSE260952 | GEO
2023-08-07 | GSE237423 | GEO
2023-08-07 | GSE237422 | GEO
2020-10-12 | GSE156449 | GEO
2022-03-08 | GSE198111 | GEO
2021-04-23 | GSE173129 | GEO
2022-07-11 | GSE207929 | GEO