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Cortical glutamic acid decarboxylase 67 deficiency results in lower cannabinoid 1 receptor messenger RNA expression: implications for schizophrenia.

Publication ,  Journal Article
Eggan, SM; Lazarus, MS; Stoyak, SR; Volk, DW; Glausier, JR; Huang, ZJ; Lewis, DA
Published in: Biol Psychiatry
January 15, 2012

BACKGROUND: Levels of cannabinoid 1 receptor (CB1R) messenger RNA (mRNA) and protein, which are expressed most heavily in the cholecystokinin class of γ-aminobutyric acid (GABA) neurons, are lower in the dorsolateral prefrontal cortex in schizophrenia, and the magnitude of these differences is strongly correlated with that for glutamic acid decarboxylase 67 (GAD(67)) mRNA, a synthesizing enzyme for GABA. However, whether this correlation reflects a cause-effect relationship is unknown. METHODS: Using quantitative in situ hybridization, we measured CB1R, GAD(67), and diacylglycerol lipase alpha (the synthesizing enzyme for the endocannabinoid 2-arachidonoylglycerol) mRNA levels in the medial prefrontal cortex of genetically engineered GAD(67) heterozygous (GAD(67)(+/-)), CB1R heterozygous (CB1R(+/-)), CB1R knockout (CB1R(-/-)), and matched wild-type mice. RESULTS: In GAD(67)(+/-) mice, GAD(67) and CB1R mRNA levels were significantly reduced by 37% and 16%, respectively, relative to wild-type mice and were significantly correlated across animals (r = .61; p = .01). In contrast, GAD(67) mRNA levels were unaltered in CB1R(+/-) andCB1R(-/-) mice. Expression of diacylglycerol lipase alpha mRNA, which is not altered in schizophrenia, was also not altered in any of the genetically engineered mice. CONCLUSIONS: The findings that reduced GAD(67) mRNA expression can induce lower CB1R mRNA expression support the hypothesis that lower cortical levels of CB1Rs in schizophrenia may partially compensate for deficient GAD(67)-mediated GABA synthesis by reducing endogenous cannabinoid suppression of GABA release.

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Published In

Biol Psychiatry

DOI

EISSN

1873-2402

Publication Date

January 15, 2012

Volume

71

Issue

2

Start / End Page

114 / 119

Location

United States

Related Subject Headings

  • Schizophrenia
  • Receptor, Cannabinoid, CB1
  • RNA, Messenger
  • Psychiatry
  • Prefrontal Cortex
  • Mice, Transgenic
  • Mice, Knockout
  • Mice
  • Male
  • Lipoprotein Lipase
 

Citation

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Eggan, S. M., Lazarus, M. S., Stoyak, S. R., Volk, D. W., Glausier, J. R., Huang, Z. J., & Lewis, D. A. (2012). Cortical glutamic acid decarboxylase 67 deficiency results in lower cannabinoid 1 receptor messenger RNA expression: implications for schizophrenia. Biol Psychiatry, 71(2), 114–119. https://doi.org/10.1016/j.biopsych.2011.09.014
Eggan, Stephen M., Matthew S. Lazarus, Samuel R. Stoyak, David W. Volk, Jill R. Glausier, Z Josh Huang, and David A. Lewis. “Cortical glutamic acid decarboxylase 67 deficiency results in lower cannabinoid 1 receptor messenger RNA expression: implications for schizophrenia.Biol Psychiatry 71, no. 2 (January 15, 2012): 114–19. https://doi.org/10.1016/j.biopsych.2011.09.014.
Eggan SM, Lazarus MS, Stoyak SR, Volk DW, Glausier JR, Huang ZJ, et al. Cortical glutamic acid decarboxylase 67 deficiency results in lower cannabinoid 1 receptor messenger RNA expression: implications for schizophrenia. Biol Psychiatry. 2012 Jan 15;71(2):114–9.
Eggan, Stephen M., et al. “Cortical glutamic acid decarboxylase 67 deficiency results in lower cannabinoid 1 receptor messenger RNA expression: implications for schizophrenia.Biol Psychiatry, vol. 71, no. 2, Jan. 2012, pp. 114–19. Pubmed, doi:10.1016/j.biopsych.2011.09.014.
Eggan SM, Lazarus MS, Stoyak SR, Volk DW, Glausier JR, Huang ZJ, Lewis DA. Cortical glutamic acid decarboxylase 67 deficiency results in lower cannabinoid 1 receptor messenger RNA expression: implications for schizophrenia. Biol Psychiatry. 2012 Jan 15;71(2):114–119.
Journal cover image

Published In

Biol Psychiatry

DOI

EISSN

1873-2402

Publication Date

January 15, 2012

Volume

71

Issue

2

Start / End Page

114 / 119

Location

United States

Related Subject Headings

  • Schizophrenia
  • Receptor, Cannabinoid, CB1
  • RNA, Messenger
  • Psychiatry
  • Prefrontal Cortex
  • Mice, Transgenic
  • Mice, Knockout
  • Mice
  • Male
  • Lipoprotein Lipase