Alterations in Brain Cannabinoid Receptor Levels Are Associated with HIV-Associated Neurocognitive Disorders in the ART Era: Implications for Therapeutic Strategies Targeting the Endocannabinoid System.
Viruses
; 13(9)2021 08 31.
Article
em En
| MEDLINE
| ID: mdl-34578323
ABSTRACT
HIV-associated neurocognitive disorders (HAND) persist despite the advent of antiretroviral therapy (ART), suggesting underlying systemic and central nervous system (CNS) inflammatory mechanisms. The endogenous cannabinoid receptors 1 and 2 (CB1 and CB2) modulate inflammatory gene expression and play an important role in maintaining neuronal homeostasis. Cannabis use is disproportionately high among people with HIV (PWH) and may provide a neuroprotective effect for those on ART due to its anti-inflammatory properties. However, expression profiles of CB1 and CB2 in the brains of PWH on ART with HAND have not been reported. In this study, biochemical and immunohistochemical analyses were performed to determine CB1 and CB2 expression in the brain specimens of HAND donors. Immunoblot revealed that CB1 and CB2 were differentially expressed in the frontal cortices of HAND brains compared to neurocognitively unimpaired (NUI) brains of PWH. CB1 expression levels negatively correlated with memory and information processing speed. CB1 was primarily localized to neuronal soma in HAND brains versus a more punctate distribution of neuronal processes in NUI brains. CB1 expression was increased in cells with glial morphology and showed increased colocalization with an astroglial marker. These results suggest that targeting the endocannabinoid system may be a potential therapeutic strategy for HAND.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
8_ODS3_consumo_sustancias_psicoactivas
Base de dados:
MEDLINE
Assunto principal:
Encéfalo
/
Infecções por HIV
/
Transtornos Neurocognitivos
/
Receptores de Canabinoides
/
Endocanabinoides
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Viruses
Ano de publicação:
2021
Tipo de documento:
Article