An association between the reduced levels of SLC1A2 and GAD1 in the dorsolateral prefrontal cortex in major depressive disorder: possible involvement of an attenuated RAF/MEK/ERK signaling pathway

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• 作者：Dong Hoon Oh (1)
  Daeyoung Oh (5)
  Hyeon Son (2)
  Maree J. Webster (3)
  Cyndi S. Weickert (4)
  Seok Hyeon Kim (1)
  
• 关键词：Glutamate transporters ; Glutamic acid decarboxylase ; MEK ERK pathway ; Dorsolateral prefrontal cortex ; Major depressive disorder
• 刊名：Journal of Neural Transmission
• 出版年：2014
• 出版时间：July 2014
• 年：2014
• 卷：121
• 期：7
• 页码：783-792
• 全文大小：478 KB
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• 作者单位：Dong Hoon Oh (1)
  Daeyoung Oh (5)
  Hyeon Son (2)
  Maree J. Webster (3)
  Cyndi S. Weickert (4)
  Seok Hyeon Kim (1)
  
  1. Department of Psychiatry, College of Medicine and Institute of Mental Health, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul, 133-791, Republic of Korea
  5. Department of Psychiatry, CHA Bundang Medical Center, CHA University School of Medicine, 59 Yatap-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, 463-712, Republic of Korea
  2. Department of Biochemistry and Molecular Biology, College of Medicine, Hanyang University, Seoul, Republic of Korea
  3. Laboratory of Brain Research, Stanley Medical Research Institute, 9800 Medical Center Drive, Rockville, MD, USA
  4. Schizophrenia Research Laboratory, Neuroscience Research Australia, Sydney, NSW, Australia
  
• ISSN：1435-1463

文摘

Previous human postmortem studies have shown that expression of glutamate transporters (SLC1A2 and SLC1A3) and gamma-aminobutyric acid-synthesizing enzyme [glutamic acid decarboxylase 1 (GAD1)] are reduced in the dorsolateral prefrontal cortex (dlPFC) in subjects with major depressive disorder (MDD). However, no studies have explored the association between these two molecules and its related biological processes in MDD because of limited postmortem sample availability. Data sharing using the Stanley neuropathology consortium integrative database (SNCID), a web-based tool that integrates datasets from the same postmortem brain samples, allowed us to reanalyze existing postmortem data efficiently. We found two datasets where the mRNA levels of GAD1 and SLC1A2 in subregions of the dlPFC were significantly and marginally lower in subjects with MDD (n?=?15) than in controls (n?=?15) (p?=?0.045 and 0.057, respectively). In addition, there was a positive correlation between these two molecules (n?=?30, p?n?=?60, p?mRNA expression and their relation to the attenuation of the RAF/MEK/ERK signaling pathway in the dlPFC in MDD. The integration of the existing archival data may shed light on one important aspect of the pathophysiology of MDD.