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• W1924066 abstract "Somatostatin is a secretory neuropeptide and marker of gamma-aminobutyric acid (GABA) interneurons that contribute to information processing of local cortical circuits. SST deficits are frequently observed in depression and other neurological disorders with mood disturbances, but the origin of SST-related pathological changes and their role in disease processes remain elusive. We used mice lacking Sst (SstKO) to investigate the contribution of low SST to anxiety/depressive-like phenotypes (defined as emotionality) under baseline and stressed conditions. High emotionality was found in SstKO mice at baseline and after unpredictable chronic mild stress exposure. Compared to wild-type mice, unstressed SstKO mice showed high basal plasma corticosterone and reduced gene expression of Bdnf, Cortistatin, and Gad67 in the cingulate cortex. Compared to pyramidal neurons, cell-specific transcriptome analyses indicated that SST neurons in the cingulate cortex are more vulnerable to chronic stress. Protein translation through eukaryotic initiation factor 2 (EIF2) signaling, a pathway previously implicated in neurodegenerative diseases, was most affected and suppressed in stress-exposed SST neurons. Activating EIF2 signaling with an EIF2 kinase inhibitor mitigated mouse anxiety/depressive-like behaviors that were induced by stress. Together, our results suggest a causal relationship between SST deficits and mood-related phenotypes by first showing that SstKO mice exhibit behavioral, neuroendocrine and molecular phenotypes parallel those seen in human patients with major depression. Our results further suggest a novel antidepressant function for EIF2-related protein translational control, and may prove important in elucidating mechanisms of how chronic stress triggers and sustains selective vulnerability of SST neurons associated with mood symptoms in stress-related neuropsychiatric disorders." @default.
• W1924066 created "2016-06-24" @default.
• W1924066 creator A5073575553 @default.
• W1924066 date "2014-06-27" @default.
• W1924066 modified "2023-09-27" @default.
• W1924066 title "CONTRIBUTION OF SOMATOSTATIN DEFICITS AND EIF2 SIGNALING TO ANXIETY/DEPRESSIVE-LIKE BEHAVIORS" @default.
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• W1924066 hasPublicationYear "2014" @default.
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