Terminal type-specific cannabinoid CB1 receptor alterations in patients with schizophrenia: a pilot study.
Journal
bioRxiv : the preprint server for biology
Titre abrégé: bioRxiv
Pays: United States
ID NLM: 101680187
Informations de publication
Date de publication:
11 Apr 2023
11 Apr 2023
Historique:
medline:
24
4
2023
pubmed:
24
4
2023
entrez:
24
04
2023
Statut:
epublish
Résumé
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. 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 diagnosed with schizophrenia and non-psychiatric comparisons. 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. 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.
Sections du résumé
Background
UNASSIGNED
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
UNASSIGNED
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 diagnosed with schizophrenia and non-psychiatric comparisons.
Results
UNASSIGNED
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
UNASSIGNED
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.
Identifiants
pubmed: 37090672
doi: 10.1101/2023.04.11.536217
pmc: PMC10120624
pii:
doi:
Types de publication
Preprint
Langues
eng
Subventions
Organisme : NIMH NIH HHS
ID : P50 MH103204
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH071533
Pays : United States
Commentaires et corrections
Type : UpdateIn
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