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Brain cannabinoid CB2 receptor in schizophrenia.
Hiroki Ishiguro1, Yasue Horiuchi, Maya Ishikawa
1Department of Medical Genetics, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan. hishigur@md.tsukuba.ac.jp
Biological Psychiatry
|November 26, 2009
Summary
Investigating the CB2 receptor
Area of Science:
- Neuroscience
- Genetics
- Psychiatry
Background:
- The endocannabinoid system, including CB1 and CB2 receptors, plays a role in brain function.
- Dysregulation of neural endocannabinoid signaling is implicated in schizophrenia.
- The specific role of the CB2 receptor in schizophrenia requires further investigation.
Purpose of the Study:
- To investigate the association between the CNR2 gene, encoding the CB2 receptor, and schizophrenia.
- To explore the functional consequences of genetic variations in CB2 receptor.
- To examine the impact of CB2 receptor antagonism on schizophrenia-relevant behaviors in a mouse model.
Main Methods:
- A case-control association study was conducted using tag single nucleotide polymorphisms (SNPs) in the CNR2 gene.
- Allelic variations were analyzed in human postmortem brain tissues and cultured cells.
- Prepulse inhibition and locomotor activity were assessed in mice following administration of a CB2 receptor antagonist.
Main Results:
- Significant associations were found between specific CNR2 SNPs and schizophrenia in two independent populations.
- The R63 allele of rs2501432 and the C allele of rs12744386, along with their haplotype, were increased in schizophrenia patients.
- Lower CB2 receptor function and expression were observed in individuals with specific genotypes, and CB2 antagonism exacerbated behavioral deficits in mice.
Conclusions:
- Genetic variations in the CNR2 gene are associated with an increased risk of schizophrenia.
- Reduced CB2 receptor function may contribute to the pathophysiology of schizophrenia.
- These findings highlight the CB2 receptor as a potential therapeutic target for schizophrenia.
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