Terminal type-specific cannabinoid CB1 receptor alterations in patients with schizophrenia: A pilot study
Background: Individuals with schizophrenia are at elevated genetic risks for comorbid cannabis use, and often experience exacerbations of cognitive and psychotic symptoms when exposed to cannabis. These findings have led a number of investigators to examine cannabinoid CB1 receptor (CB1R) alteration...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-09-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996123002772 |
| _version_ | 1827855749675483136 |
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| author | Shinnyi Chou Kenneth N. Fish David A. Lewis Robert A. Sweet |
| author_facet | Shinnyi Chou Kenneth N. Fish David A. Lewis Robert A. Sweet |
| author_sort | Shinnyi Chou |
| collection | DOAJ |
| description | Background: Individuals with schizophrenia are at elevated genetic risks for comorbid cannabis use, and often experience exacerbations of cognitive and psychotic symptoms when exposed to cannabis. These findings have led a number of investigators to examine cannabinoid CB1 receptor (CB1R) alterations in schizophrenia, though with conflicting results. We recently demonstrated the presence of CB1R in both excitatory and inhibitory boutons in the human prefrontal cortex, with differential levels of the receptor between bouton types. We hypothesized that the differential enrichment of CB1R between bouton types – a factor previously unaccounted for when examining CB1R changes in schizophrenia – may resolve prior discrepant reports and increase our insight into the effects of CB1R alterations on the pathophysiology of schizophrenia. Methods: Using co-labeling immunohistochemistry and fluorescent microscopy, we examined total CB1R levels and CB1R levels within excitatory (vGlut1-positive) and inhibitory (vGAT-positive) boutons of prefrontal cortex samples from ten pairs of individuals (nine male pairs and one female pair) diagnosed with schizophrenia and non-psychiatric comparisons. Results: Significantly higher total CB1R levels were found within samples from individuals with schizophrenia. Terminal type-specific analyses identified significantly higher CB1R levels within excitatory boutons in samples from individuals with schizophrenia relative to comparisons. In contrast, CB1R levels within the subset of inhibitory boutons that normally express high CB1R levels (presumptive cholecystokinin neuron boutons) were lower in samples from individuals with schizophrenia relative to comparison samples. Conclusion: Given CB1R's role in suppressing neurotransmission upon activation, these results suggest an overall shift in excitatory and inhibitory balance regulation toward a net reduction of excitatory activity in schizophrenia. |
| first_indexed | 2024-03-12T11:55:19Z |
| format | Article |
| id | doaj.art-fcf61b4ab41b4d589a3f04713eecfb53 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-03-12T11:55:19Z |
| publishDate | 2023-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-fcf61b4ab41b4d589a3f04713eecfb532023-08-31T05:00:32ZengElsevierNeurobiology of Disease1095-953X2023-09-01185106262Terminal type-specific cannabinoid CB1 receptor alterations in patients with schizophrenia: A pilot studyShinnyi Chou0Kenneth N. Fish1David A. Lewis2Robert A. Sweet3Translational Neuroscience Program, Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, United States of AmericaTranslational Neuroscience Program, Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, United States of AmericaTranslational Neuroscience Program, Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, United States of AmericaCorresponding author.; Translational Neuroscience Program, Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, United States of AmericaBackground: Individuals with schizophrenia are at elevated genetic risks for comorbid cannabis use, and often experience exacerbations of cognitive and psychotic symptoms when exposed to cannabis. These findings have led a number of investigators to examine cannabinoid CB1 receptor (CB1R) alterations in schizophrenia, though with conflicting results. We recently demonstrated the presence of CB1R in both excitatory and inhibitory boutons in the human prefrontal cortex, with differential levels of the receptor between bouton types. We hypothesized that the differential enrichment of CB1R between bouton types – a factor previously unaccounted for when examining CB1R changes in schizophrenia – may resolve prior discrepant reports and increase our insight into the effects of CB1R alterations on the pathophysiology of schizophrenia. Methods: Using co-labeling immunohistochemistry and fluorescent microscopy, we examined total CB1R levels and CB1R levels within excitatory (vGlut1-positive) and inhibitory (vGAT-positive) boutons of prefrontal cortex samples from ten pairs of individuals (nine male pairs and one female pair) diagnosed with schizophrenia and non-psychiatric comparisons. Results: Significantly higher total CB1R levels were found within samples from individuals with schizophrenia. Terminal type-specific analyses identified significantly higher CB1R levels within excitatory boutons in samples from individuals with schizophrenia relative to comparisons. In contrast, CB1R levels within the subset of inhibitory boutons that normally express high CB1R levels (presumptive cholecystokinin neuron boutons) were lower in samples from individuals with schizophrenia relative to comparison samples. Conclusion: Given CB1R's role in suppressing neurotransmission upon activation, these results suggest an overall shift in excitatory and inhibitory balance regulation toward a net reduction of excitatory activity in schizophrenia.http://www.sciencedirect.com/science/article/pii/S0969996123002772Cannabinoid receptorCB1Cell typePostmortemPrefrontal cortexSchizophrenia |
| spellingShingle | Shinnyi Chou Kenneth N. Fish David A. Lewis Robert A. Sweet Terminal type-specific cannabinoid CB1 receptor alterations in patients with schizophrenia: A pilot study Neurobiology of Disease Cannabinoid receptor CB1 Cell type Postmortem Prefrontal cortex Schizophrenia |
| title | Terminal type-specific cannabinoid CB1 receptor alterations in patients with schizophrenia: A pilot study |
| title_full | Terminal type-specific cannabinoid CB1 receptor alterations in patients with schizophrenia: A pilot study |
| title_fullStr | Terminal type-specific cannabinoid CB1 receptor alterations in patients with schizophrenia: A pilot study |
| title_full_unstemmed | Terminal type-specific cannabinoid CB1 receptor alterations in patients with schizophrenia: A pilot study |
| title_short | Terminal type-specific cannabinoid CB1 receptor alterations in patients with schizophrenia: A pilot study |
| title_sort | terminal type specific cannabinoid cb1 receptor alterations in patients with schizophrenia a pilot study |
| topic | Cannabinoid receptor CB1 Cell type Postmortem Prefrontal cortex Schizophrenia |
| url | http://www.sciencedirect.com/science/article/pii/S0969996123002772 |
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