| Autor: |
Chiranjivi Neupane, Ramesh Sharma, Fei Fei Gao, Thuy Linh Pham, Yoo Sung Kim, Bo-Eun Yoon, Eun-Kyeong Jo, Kyung-Cheol Sohn, Gang Min Hur, Guang-Ho Cha, Sun Seek Min, Cuk-Seong Kim, Jin Bong Park |
| Předmět: |
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| Zdroj: |
Journal of Neuroscience; 10/9/2024, Vol. 44 Issue 41, p1-16, 16p |
| Abstrakt: |
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 STING→GAT 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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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