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Open Access 01-12-2017 | Original Article

Increased glutamic acid decarboxylase expression in the hypothalamic suprachiasmatic nucleus in depression

Authors: Xueyan Wu, Rawien Balesar, Jing Lu, Sahar Farajnia, Qiongbin Zhu, Manli Huang, Ai-Min Bao, Dick F. Swaab

Published in: Brain Structure and Function | Issue 9/2017

Abstract

In depression, disrupted circadian rhythms reflect abnormalities in the central circadian pacemaker, the hypothalamic suprachiasmatic nucleus (SCN). Although many SCN neurons are said to be GABAergic, it was not yet known whether and how SCN GABA changes occur in the SCN in depression. We, therefore, studied GABA in the SCN in relation to the changes in arginine vasopressin (AVP), which is one of the major SCN output systems. Postmortem hypothalamus specimens of 13 subjects suffering from depression and of 13 well-matched controls were collected. Quantitative immunocytochemistry was used to analyze the protein levels of glutamic acid decarboxylase (GAD)65/67 and AVP, and quantitative in situ hybridization was used to measure transcript levels of GAD67 in the SCN. There were a significant 58% increase of SCN GAD65/67-ir and a significant 169% increase of SCN GAD67-mRNA in the depression group. In addition, there were a significant 253% increase of AVP-ir in female depression subjects but not in male depression patients. This sex difference was supported by a re-analysis of SCN AVP-ir data of a previous study of our group. Moreover, SCN-AVP-ir showed a significant negative correlation with age in the control group and in the male, but not in the female depression group. Given the crucial role of GABA in mediating SCN function, our finding of increased SCN GABA expression may significantly contribute to the disordered circadian rhythms in depression. The increased SCN AVP-ir in female—but not in male-depression patients—may reflect the higher vulnerability for depression in women.

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Title: Increased glutamic acid decarboxylase expression in the hypothalamic suprachiasmatic nucleus in depression
Authors: Xueyan Wu
Rawien Balesar
Jing Lu
Sahar Farajnia
Qiongbin Zhu
Manli Huang
Ai-Min Bao
Dick F. Swaab
Publication date: 01-12-2017
Publisher: Springer Berlin Heidelberg
Published in: Brain Structure and Function / Issue 9/2017
Print ISSN: 1863-2653
Electronic ISSN: 1863-2661
DOI: https://doi.org/10.1007/s00429-017-1442-y

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Increased glutamic acid decarboxylase expression in the hypothalamic suprachiasmatic nucleus in depression

Abstract

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Abstract

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