Neurocognitive implications of cannabidiol (CBD) while aging with HIV

大麻二酚 (CBD) 在艾滋病毒衰老过程中对神经认知的影响

• 批准号: 10548522
• 负责人: Myosotys Rodriguez
• 金额: $ 14.75万
• 依托单位: FLORIDA INTERNATIONAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10548522
• 关键词: Adult; Affect; Age; Aging; Alzheimer' s Disease; Alzheimer' s disease model; Animals; Anti-Inflammatory Agents; Anti-Retroviral Agents; Anxiety; Astrocytes; Autopsy; Behavior assessment; Brain; CNR1 gene; Cannabidiol; Cannabinoids; Cannabis; Cell Aging; Characteristics; Chronic; Clinical; Cognition; Cognitive deficits; Conflict (Psychology); Consumption; Cyclin-Dependent Kinase Inhibitor; Dementia; Development; Disease; Drug Kinetics; Effectiveness; Elderly; Exposure to; Female; Flow Cytometry; Fractals; General Population; Genes; Goals; HIV; HIV Infections; HIV Seropositivity; Histologic; Immune; Immunohistochemistry; In Vitro; Individual; Inflammaging; Inflammation; Intervention; JAK2 gene; Learning; Life Expectancy; Liquid Chromatography; Longevity; Measures; Mediating; Medical; Medical Marijuana; Memory; Methodology; Molecular; Morphology; Mus; Nerve Degeneration; Neurocognitive; Neurocognitive Deficit; Neurologic Deficit; Opioid; Organ; Pain management; Parkinson Disease; Pathway interactions; Patients; Persons; Phenotype; Play; Population; Premature aging syndrome; Process; Property; Regimen; Reporting; Rest; Reverse Transcriptase Polymerase Chain Reaction; Risk; Role; STAT1 gene; Serum; TP53 gene; Testing; Therapeutic; Viral; Viral Load result; Walkers; Western Blotting; age related; aged; aging brain; aging population; antiretroviral therapy; behavior test; brain tissue; chronic pain management; cognitive change; comorbidity; emtricitabine; experience; experimental study; human old age (65+); immune activation; immunosenescence; improved; in vivo; male; marijuana use; marijuana user; memory recognition; mitochondrial membrane; mouse model; neuroAIDS; neuroinflammation; non-drug; normal aging; novel; object recognition; older patient; pre-clinical; premature; prevent; prospective; senescence; success; tandem mass spectrometry; therapeutic target

PROJECT SUMMARY The success of combined antiretroviral therapy (cART) has drastically improved the life expectancy of people living with HIV. This has resulted in the clinical observations of significant age-related neurocognitive complications among the population aging with HIV. HIV-associated inflammation has been implicated in premature aging and increased risk of age-associated comorbidities even in cART-treated individuals. Currently, people living with HIV are using cannabis, for recreational or medical purposes, at higher rates than the general population. However, cannabinoids in the context of HIV and aging remain preclinically unexplored. As the use of medical cannabis among older HIV individuals continues to rise, there is an urgent need to investigate the consequences of cannabinoids during aging with HIV. The goal of this proposal is to unravel the beneficial versus the detrimental effects of cannabinoids on HIV and HIV-induced neurocognitive deficits in aged mice. It has been shown that cannabidiol (CBD) improves both spatial and recognition memory and decreases anxiety in a mouse model of Alzheimer’s disease, suggesting its therapeutic potential for age‐related dementia. Therefore, we hypothesize that exposure to CBD will modulate neuroinflammation and cognitive deficits in mice that aged with HIV. To test this hypothesis, C57BL/6J male and female adult mice (at 16-months old) will be infected with the mouse-tropic HIV, EcoHIV. After 8 weeks (at 18-months old), a subset of EcoHIV-infected mice will be exposed to CBD alone, antiretrovirals alone, and concomitant CBD and antiretrovirals for 21 days. In Specific Aim 1, we posit that CBD will modulate HIV- and age-associated cognitive deficits, specifically memory, and learning functions, measured by the novel object recognition test and the Y-maze behavioral test. In Specific Aim 2, we posit that CBD exposure will modulate neuroinflammation, glial phenotypes, and cellular senescence in postmortem brain tissue of EcoHIV-infected and aged mice recovered in Specific Aim 1. The experiments described in this proposal will allow us to determine the molecular mechanisms that could mediate the consequences of cannabinoids exposure in the HIV-infected aged brain. The ultimate goal of this project is to identify a potential therapeutic target that could reduce age-related neurodegenerative deficits associated with chronic HIV infection.

项目总结