FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4387449940> ?p ?o ?g. }

• W4387449940 endingPage "23.2023" @default.
• W4387449940 startingPage "ENEURO.0162" @default.
• W4387449940 abstract "Depression is a frequent and serious illness and stress is considered the main risk factor for its onset. First-line antidepressants increase serotonin (5-hydroxytryptamine and 5-HT) levels in the brain. We previously reported that an N -acetyltransferase, Shati/Nat8l, is upregulated in the dorsal striatum (dSTR) of stress-susceptible mice exposed to repeated social defeat stress (RSDS) and that dSTR Shati/Nat8l overexpression in mice (dSTR-Shati OE) induces stress vulnerability and local reduction in 5-HT content. Male mice were used in this study, and we found that dSTR 5-HT content decreased in stress-susceptible but not in resilient mice. Moreover, vulnerability to stress in dSTR-Shati OE mice was suppressed by the activation of serotonergic neurons projecting from the dorsal raphe nucleus (dRN) to the dSTR, followed by upregulation of 5-HT content in the dSTR using designer receptors exclusively activated by designer drugs (DREADD). We evaluated the role of GABA in modulating the serotonergic system in the dRN. Stress-susceptible after RSDS and dSTR-Shati OE mice exhibited an increase in dRN GABA content. Furthermore, dRN GABA content was correlated with stress sensitivity. We found that the blockade of GABA signaling in the dRN suppressed stress susceptibility in dSTR-Shati OE mice. In conclusion, we propose that dSTR 5-HT and dRN GABA, controlled by striatal Shati/Nat8l via the dSTR-dRN neuronal circuitry, critically regulate stress sensitivity. Our study provides insights into the neural processes that underlie stress and suggests that dSTR Shati/Nat8l could be a novel therapeutic target for drugs against depression, allowing direct control of the dRN serotonergic system. Significance Statement Given that 30% of depression patients have resistant to conventional antidepressants, finding novel therapeutic strategies for its disease is required. We previously demonstrated that the overexpression of Shati/Nat8l, N -acetyltransferase, in the dorsal striatum (dSTR) of mice induces stress vulnerability. dSTR 5-HT (5-hydroxytryptamine and 5-HT) levels are downregulated in stress-susceptible, non-resilient mice exposed to repeated social defeat stress. Stress vulnerability in dSTR Shati/Nat8l overexpression mice was suppressed by the activation of serotonergic neurons projecting from the dorsal raphe nucleus (dRN) to the dSTR. We discovered that dRN GABA content correlated with stress sensitivity and inhibited GABA signaling in dRN-induced stress resilience. We suggest that novel bidirectional dSTR-dRN circuits determine the stress sensitivity underlying depression pathology." @default.
• W4387449940 created "2023-10-10" @default.
• W4387449940 creator A5017641271 @default.
• W4387449940 creator A5027509774 @default.
• W4387449940 creator A5047756030 @default.
• W4387449940 creator A5060591351 @default.
• W4387449940 creator A5069754613 @default.
• W4387449940 creator A5072554548 @default.
• W4387449940 creator A5085780525 @default.
• W4387449940 creator A5093027195 @default.
• W4387449940 date "2023-10-09" @default.
• W4387449940 modified "2023-10-13" @default.
• W4387449940 title "The role of GABA in the in the dorsal striatum-raphe nucleus circuit regulating stress vulnerability in male mice with high levels of Shati/Nat8l" @default.
• W4387449940 doi "https://doi.org/10.1523/eneuro.0162-23.2023" @default.
• W4387449940 hasPublicationYear "2023" @default.
• W4387449940 type Work @default.
• W4387449940 citedByCount "0" @default.
• W4387449940 crossrefType "journal-article" @default.
• W4387449940 hasAuthorship W4387449940A5017641271 @default.
• W4387449940 hasAuthorship W4387449940A5027509774 @default.
• W4387449940 hasAuthorship W4387449940A5047756030 @default.
• W4387449940 hasAuthorship W4387449940A5060591351 @default.
• W4387449940 hasAuthorship W4387449940A5069754613 @default.
• W4387449940 hasAuthorship W4387449940A5072554548 @default.
• W4387449940 hasAuthorship W4387449940A5085780525 @default.
• W4387449940 hasAuthorship W4387449940A5093027195 @default.
• W4387449940 hasBestOaLocation W43874499401 @default.
• W4387449940 hasConcept C126322002 @default.
• W4387449940 hasConcept C134018914 @default.
• W4387449940 hasConcept C15744967 @default.
• W4387449940 hasConcept C169760540 @default.
• W4387449940 hasConcept C170493617 @default.
• W4387449940 hasConcept C2775864247 @default.
• W4387449940 hasConcept C2780062018 @default.
• W4387449940 hasConcept C32610206 @default.
• W4387449940 hasConcept C37000724 @default.
• W4387449940 hasConcept C513476851 @default.
• W4387449940 hasConcept C71924100 @default.
• W4387449940 hasConcept C86803240 @default.
• W4387449940 hasConceptScore W4387449940C126322002 @default.
• W4387449940 hasConceptScore W4387449940C134018914 @default.
• W4387449940 hasConceptScore W4387449940C15744967 @default.
• W4387449940 hasConceptScore W4387449940C169760540 @default.
• W4387449940 hasConceptScore W4387449940C170493617 @default.
• W4387449940 hasConceptScore W4387449940C2775864247 @default.
• W4387449940 hasConceptScore W4387449940C2780062018 @default.
• W4387449940 hasConceptScore W4387449940C32610206 @default.
• W4387449940 hasConceptScore W4387449940C37000724 @default.
• W4387449940 hasConceptScore W4387449940C513476851 @default.
• W4387449940 hasConceptScore W4387449940C71924100 @default.
• W4387449940 hasConceptScore W4387449940C86803240 @default.
• W4387449940 hasFunder F4320334764 @default.
• W4387449940 hasLocation W43874499401 @default.
• W4387449940 hasOpenAccess W4387449940 @default.
• W4387449940 hasPrimaryLocation W43874499401 @default.
• W4387449940 hasRelatedWork W1972622243 @default.
• W4387449940 hasRelatedWork W1976200965 @default.
• W4387449940 hasRelatedWork W1990448043 @default.
• W4387449940 hasRelatedWork W2014541695 @default.
• W4387449940 hasRelatedWork W2027364088 @default.
• W4387449940 hasRelatedWork W2067625942 @default.
• W4387449940 hasRelatedWork W2072185657 @default.
• W4387449940 hasRelatedWork W2081701126 @default.
• W4387449940 hasRelatedWork W2089046934 @default.
• W4387449940 hasRelatedWork W2160840055 @default.
• W4387449940 isParatext "false" @default.
• W4387449940 isRetracted "false" @default.
• W4387449940 workType "article" @default.