Role of the STINGâIRF3 Pathway in Ambient GABA Homeostasis and Cognitive Function.
J Neurosci
; 44(41)2024 Oct 09.
Article
in En
| MEDLINE
| ID: mdl-39227159
ABSTRACT
Targeting altered expression and/or activity of GABA (γ-aminobutyric acid) transporters (GATs) provide therapeutic benefit for age-related impairments, including cognitive dysfunction. However, the mechanisms underlying the transcriptional regulation of GATs are unknown. In the present study, we demonstrated that the stimulator of interferon genes (STING) upregulates GAT1 and GAT3 expression in the brain, which resulted in cognitive dysfunction. Genetic and pharmacological intervention of STING suppressed the expression of both GAT1 and GAT3, increased the ambient GABA concentration, and therefore, enhanced tonic GABAA inhibition of principal hippocampal neurons, resulting in spatial learning and working memory deficits in mice in a type I interferon-independent manner. Stimulation of the STINGâGAT pathway efficiently restored cognitive dysfunction in STING-deficient mice models. Our study uncovered for the first time that the STING signaling pathway regulates GAT expression in a cell autonomous manner and therefore could be a novel target for GABAergic cognitive deficits.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Signal Transduction
/
Interferon Regulatory Factor-3
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GABA Plasma Membrane Transport Proteins
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Gamma-Aminobutyric Acid
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Homeostasis
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Membrane Proteins
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Mice, Inbred C57BL
Limits:
Animals
Language:
En
Journal:
J Neurosci
/
J. neurosci
/
Journal of neuroscience
Year:
2024
Type:
Article