Transient astrocytic mGluR5 expression drives synaptic plasticity and subsequent chronic pain in mice.
Journal
The Journal of experimental medicine
ISSN: 1540-9538
Titre abrégé: J Exp Med
Pays: United States
ID NLM: 2985109R
Informations de publication
Date de publication:
04 04 2022
04 04 2022
Historique:
received:
07
05
2021
revised:
03
01
2022
accepted:
31
01
2022
entrez:
23
3
2022
pubmed:
24
3
2022
medline:
3
5
2022
Statut:
ppublish
Résumé
Activation of astrocytes has a profound effect on brain plasticity and is critical for the pathophysiology of several neurological disorders including neuropathic pain. Here, we show that metabotropic glutamate receptor 5 (mGluR5), which reemerges in astrocytes in a restricted time frame, is essential for these functions. Although mGluR5 is absent in healthy adult astrocytes, it transiently reemerges in astrocytes of the somatosensory cortex (S1). During a limited spatiotemporal time frame, astrocytic mGluR5 drives Ca2+ signals; upregulates multiple synaptogenic molecules such as Thrombospondin-1, Glypican-4, and Hevin; causes excess excitatory synaptogenesis; and produces persistent alteration of S1 neuronal activity, leading to mechanical allodynia. All of these events were abolished by the astrocyte-specific deletion of mGluR5. Astrocytes dynamically control synaptic plasticity by turning on and off a single molecule, mGluR5, which defines subsequent persistent brain functions, especially under pathological conditions.
Identifiants
pubmed: 35319723
pii: 213089
doi: 10.1084/jem.20210989
pmc: PMC8952801
pii:
doi:
Substances chimiques
Grm5 protein, mouse
0
Receptor, Metabotropic Glutamate 5
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2022 Danjo et al.
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