Increased cannabinoid receptor density in the posterior cingulate cortex in schizophrenia

Newell, Kelly A.; Deng, Chao; Huang, Xu‐Feng

doi:10.1007/s00221-006-0503-x

Cited by 165 publications

(107 citation statements)

References 28 publications

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“…Increased cannabinoid CB1 receptor density in the dorsolateral prefrontal, anterior and posterior cingulate cortex supported this postulation [11][12][13] . The STG is involved in the pathology of schizophrenia, particularly in auditory hallucination [14,[22][23][24] .…”

Section: Subjectsmentioning

confidence: 64%

“…2B) binding showed a homogeneous labelling through all cortical layers of the STG [12,15] . Even though the two ligands showed different binding patterns in the cortex, previous studies have shown that both of them are suitable to reveal the alteration of CB1 receptor density in schizophrenia [11][12][13] . A previous study in our laboratory identified an increase in the binding density of [ 3 H]SR141716A in the anterior cingulate cortex of schizophrenia patients [12] , utilising tissue mostly obtained from subjects used in the present study (all 8 schizophrenia patients and 7 of 8 control cases).…”

Section: Subjectsmentioning

confidence: 98%

“…For example, two endogenous cannabinoid agonists (anandamide and palmitylethanolamide) were found to be significantly higher in the cerebrospinal fluid of schizophrenic patients [9,10] . In post-mortem brain studies, it has been reported that schizophrenic patients had an increased density of cannabinoid CB1 receptors in the dorsolateral prefrontal cortex [11] , and anterior and posterior cingulate cortex [12,13] . There is substantial evidence to support that the superior temporal gyrus (STG) is involved in the pathology of schizophrenia, particularly in auditory hallucination [14] .…”

Section: Introductionmentioning

confidence: 99%

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No changes in densities of cannabinoid receptors in the superior temporal gyrus in schizophrenia

2007

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Objective In recent years, abnormal changes in the endocannabinoid system have been found in schizophrenia. The superior temporal gyrus (STG) is strongly implicated in the pathophysiology of schizophrenia, particularly with regards to auditory hallucinations. In this study, we investigated the binding density of cannabinoid CB1 receptors in the STG of schizophrenia patients compared to control subjects.

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Section: Subjectsmentioning

confidence: 64%

Section: Subjectsmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

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No changes in densities of cannabinoid receptors in the superior temporal gyrus in schizophrenia

2007

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“…Brains were immediately removed, frozen in liquid nitrogen and stored at -80°C. Three sites of the brain (the PFC, Cg, and hippocampus) involved in the pathophysiology of schizophrenia and antipsychotic therapeutics (Ginovart and Kapur, 2012;Lewis and Gonzalez-Burgos, 2006;Newell et al, 2006;Newell et al, 2005;Volk et al, 2010) were dissected to detect NRG1 and ErbB4 protein expression. In addition, abnormal expression of NRG1 and ErbB4 has been identified in the PFC and hippocampus of schizophrenia patients (Chong et al, 2008;Law et al, 2006).…”

Section: Western Blottingmentioning

confidence: 99%

“…Therefore, although the results from post-mortem studies are not completely consistent, evidence from the majority of studies implied an elevation in NRG1-ErbB4 signalling in schizophrenia (Hahn, 2011;Pan et al, 2011). In addition, the cingulate cortex (Cg) is also involved in the pathophysiology of schizophrenia (Natesan et al, 2006;Newell et al, 2006;Newell et al, 2005). A recent animal study indicated that mutation in the NRG1 transmembrane domain altered the expression of glutamatergic receptors in the Cg .…”

Section: Introductionmentioning

confidence: 99%

Differential effects of short- and long-term antipsychotic treatment on the expression of neuregulin-1 and ErbB4 receptors in the rat brain

Deng

Pan

et al. 2015

Psychiatry Research

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Neuregulin-1 (NRG1) and ErbB4 genes have been identified as candidate genes for schizophrenia. Postmortem studies indicated that NRG1-ErbB4 signalling is impaired in schizophrenia subjects. This study investigated whether short-or long-term antipsychotic treatment has different effects on the expression of NRG1 and ErbB4 receptors. Female Sprague-Dawley rats were treated orally with either aripiprazole (0.75 mg/kg), haloperidol (0.1 mg/kg), olanzapine (0.5 mg/kg), or vehicle, 3 times/day for 1 or 12 weeks. Western blotting was performed to examine the expression of NRG1 isoforms (135 kDa, 70 kDa and 40 kDa) and ErbB4 receptors. Both 1-week haloperidol and olanzapine treatment increased NRG1-70 kDa expression in the hippocampus; haloperidol also up-regulated ErbB4 levels in the prefrontal cortex (PFC). In the 12-week group, aripiprazole decreased the expression of all three NRG1 isoforms and ErbB4 receptors in the PFC, NRG1-70 kDa and -40 kDa in the cingulate cortex (Cg), and NRG1-135 kDa, -70 kDa and ErbB4 receptors in the hippocampus; haloperidol reduced NRG1-135 kDa in the PFC, NRG1-40 kDa in all three brain regions, and ErbB4 receptor levels in the PFC and hippocampus; NRG1-40 kDa in the PFC and Cg was also downregulated by olanzapine. These results suggest that the time-dependent and region-specific effects of antipsychotics on NRG1-ErbB4 signalling may contribute to the efficacy of antipsychotics to treat schizophrenia. AbstractNeuregulin-1 (NRG1) and ErbB4 genes have been identified as candidate genes for schizophrenia. Post-mortem studies indicated that NRG1-ErbB4 signalling is impaired in schizophrenia subjects. This study investigated whether short-or long-term antipsychotic treatment has different effects on the expression of NRG1 and ErbB4 receptors. Female Sprague-Dawley rats were treated orally with either aripiprazole (0.75mg/kg), haloperidol (0.1mg/kg), olanzapine (0.5mg/kg), or vehicle, 3 times/day for 1 or 12 weeks. Western blotting was performed to examine the expression of NRG1 isoforms (135kDa, 70kDa and 40kDa) and ErbB4 receptors. Both 1-week haloperidol and olanzapine treatment increased NRG1-70kDa expression in the hippocampus; haloperidol also up-regulated ErbB4 levels in the prefrontal cortex (PFC). In the 12-week group, aripiprazole decreased the expression of all three NRG1 isoforms and ErbB4 receptors in the PFC, NRG1-70kDa and -40kDa in the cingulate cortex (Cg), and NRG1-135kDa, -70kDa and ErbB4 receptors in the hippocampus; haloperidol reduced NRG1-135kDa in the PFC, NRG1-40kDa in all three brain regions, and ErbB4 receptor levels in the PFC and hippocampus; NRG1-40kDa in the PFC and Cg was also down-regulated by olanzapine. These results suggest that the time-dependent and regionspecific effects of antipsychotics on NRG1-ErbB4 signalling may contribute to the efficacy of antipsychotics to treat schizophrenia.

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Reduced Cortical Cannabinoid 1 Receptor Messenger RNA and Protein Expression in Schizophrenia

Eggan

Hashimoto²,

Lewis³

2008

Arch Gen Psychiatry

205

197

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Context Cannabis use is associated with both impaired cognitive functions, including working memory, and an increased risk of schizophrenia. Schizophrenia is characterized by impairments in working memory that are associated with reduced γ-aminobutyric acid (GABA) neurotransmission in the dorsolateral prefrontal cortex. The cannabinoid 1 receptor (CB1R) is highly expressed in the dorsolateral prefrontal cortex, is contained in the axon terminals of a subpopulation of perisomatic-targeting GABA neurons, and, when activated, suppresses the release of GABA. Objective To determine the potential relationship between CB1R signaling and altered GABA neurotransmission in schizophrenia by evaluating CB1R messenger RNA (mRNA) and protein expression in the dorsolateral pre-frontal cortex. Design In situ hybridization and immunocytochemistry techniques were used to examine the cortical levels of CB1R mRNA and protein, respectively. Setting Brain specimens were obtained from autopsies conducted at the Allegheny County Medical Examiner’s Office, Pittsburgh, Pennsylvania. Participants Postmortem brain specimens from 23 pairs of subjects with schizophrenia and age-, sex-, and postmortem interval–matched comparison subjects, as well as brain specimens from 18 macaque monkeys with long-term exposure to haloperidol, olanzapine, or placebo. Main Outcome Measures Optical density measures of CB1R mRNA expression and protein levels and correlations with previously reported glutamic acid decarboxylase 67 and cholecystokinin mRNA measures. Results Levels of CB1R mRNA were significantly lower by 14.8% in the subjects with schizophrenia. Similarly, CB1R protein levels, assessed by radioimmunocytochemistry and standard immunocytochemistry, were significantly decreased by 11.6% and 13.9%, respectively. Group differences in CB1R mRNA levels were significantly correlated with those in glutamic acid decarboxylase 67 and cholecystokinin mRNA levels. Expression of CB1R mRNA was not changed in antipsychotic-exposed monkeys, and neither CB1R mRNA levels nor protein levels were affected by potential confounding factors in the subjects with schizophrenia. Conclusions This combination of findings suggests the testable hypothesis that reduced CB1R mRNA and protein levels in schizophrenia represent a compensatory mechanism to increase GABA transmission from perisomatic-targeting cholecystokinin interneurons with impaired GABA synthesis.

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Increased cannabinoid receptor density in the posterior cingulate cortex in schizophrenia

Cited by 165 publications

References 28 publications

No changes in densities of cannabinoid receptors in the superior temporal gyrus in schizophrenia

No changes in densities of cannabinoid receptors in the superior temporal gyrus in schizophrenia

Differential effects of short- and long-term antipsychotic treatment on the expression of neuregulin-1 and ErbB4 receptors in the rat brain

Reduced Cortical Cannabinoid 1 Receptor Messenger RNA and Protein Expression in Schizophrenia

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