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Excessive activation of the loop between the NR2B subunit of the N-methyl-d-aspartate receptor and glycogen synthase kinase-3β in the hippocampi of patients with major depressive disorder

Published online by Cambridge University Press:  24 June 2014

Dong Hoon Oh ,
Seon-Cheol Park ,
Yong Chon Park  and
Seok Hyeon Kim
Dong Hoon Oh
Affiliation:
Department of Neuropsychiatry, College of Medicine and Institute of Mental Health, Hanyang University, Seoul, Korea
Seon-Cheol Park
Affiliation:
Department of Neuropsychiatry, College of Medicine and Institute of Mental Health, Hanyang University, Seoul, Korea
Yong Chon Park
Affiliation:
Department of Neuropsychiatry, College of Medicine and Institute of Mental Health, Hanyang University, Seoul, Korea
Seok Hyeon Kim*
Affiliation:
Department of Neuropsychiatry, College of Medicine and Institute of Mental Health, Hanyang University, Seoul, Korea
*
Professor Seok Hyeon Kim, Department of Neuropsychiatry, College of Medicine and Institute of Mental Health, Hanyang University, Haengdang 1-dong, Seongdong-gu, Seoul 133-792, Korea. Tel: +82 2 2290 8426; Fax: +82 2 2298 2055; E-mail: shkim1219@hanyang.ac.kr
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Extract

Objective: We showed previously that glycogen synthase kinase-3β (GSK-3β) levels are significantly elevated in the hippocampi of patients with major depressive disorder (MDD). However, the exact cause of this elevation and its function are unknown. Recent animal studies have suggested a mechanism involving the N-methyl-d-aspartate (NMDA) NR2B–GSK-3β loop.

Methods: To investigate the existence of an NR2B–GSK-3β loop in the hippocampi of patients with MDD, we examined the expression of NR2B. We also attempted to identify markers that correlate with NR2B levels in the hippocampus, using the Stanley Neuropathology Consortium Integrative Database (SNCID). The SNCID is a web-based tool used to integrate Stanley Medical Research Institute (SMRI) data sets.

Results: We found that hippocampal levels of NR2B and DLGAP1 mRNA were higher in the MDD group (n = 8) than in unaffected controls (n = 12) (p < 0.05). NR2B expression levels were correlated with the expression levels of NR2A, NR1, DLGAP1, GSK-3β and nitric oxide synthase 1, as well as with the number of calretinin-immunoreactive neurons in the hippocampus in all subjects in the SNC (n = 42, p < 0.001).

Conclusion: The results of our study show the possible involvement of excessive activation of the NR2B–GSK-3β loop in the overexpression of GSK-3β in the hippocampi of patients with MDD.

Keywords

data miningglycogen synthase kinase-3βhippocampusmajor depressive disorderN-methyl-d-aspartate receptor
Type
Research Article
Information
Acta Neuropsychiatrica , Volume 24 , Issue 1 , February 2012 , pp. 26 - 33
Copyright
Copyright © Cambridge University Press 2011

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