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Abnormalities of the serotonergic system in diacylglycerol kinase δ-deficient mouse brain

Journal Article · · Biochemical and Biophysical Research Communications
; ; ; ;  [1]
  1. Department of Chemistry, Graduate School of Science, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba, 263-8522 (Japan)
Highlights: • DGKδ deficiency increased SERT protein levels in the mouse cerebral cortex. • DGKδ interacted and co-localized with SERT. • DGKδ deficiency decreased TPH-2 expression and increased MAO-A expression. • The amount of 5-HT was significantly decreased in DGKδ-deficient mice. • OCD-like behaviors in DGKδ-KO mice are caused by composite serotonergic hypofunction. We previously reported that brain-specific diacylglycerol kinase (DGK) δ-knockout (KO) mice showed obsessive-compulsive disorder (OCD)-like behaviors, which were alleviated by a serotonin (5-HT) transporter (SERT) inhibitor. However, the molecular mechanisms causing the OCD-like abnormal behaviors remain unclear. In the present study, we found that DGKδ deficiency increased SERT protein levels in the mouse cerebral cortex. Moreover, DGKδ interacted and co-localized with SERT. Furthermore, DGKδ-KO decreased tryptophan hydroxylase-2 expression and increased monoamine oxidase-A expression. Indeed, the amount of 5-HT in the cerebral cortex was significantly decreased in DGKδ-KO mice. These data strongly suggest that OCD-like behaviors in the DGKδ-KO mice are caused by comprehensive and composite serotonergic hypofunction.
OSTI ID:
23137274
Journal Information:
Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 4 Vol. 497; ISSN 0006-291X; ISSN BBRCA9
Country of Publication:
United States
Language:
English

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