Effects of cannabis on age-related cognitive decline and Alzheimers disease pathology

大麻对与年龄相关的认知能力下降和阿尔茨海默病病理学的影响

• 批准号: 10633300
• 负责人: JENNIFER Lynn BIZON
• 金额: $ 67.68万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-15 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10633300
• 关键词: Acute; Address; Affect; Age; Age-associated memory impairment; Aging; Agitation; Alzheimer like pathology; Alzheimer' s Disease; Alzheimer' s disease pathology; Anorexia; Anxiety; Attenuated; Behavioral; Behavioral Symptoms; Biochemical; Brain; Cannabinoids; Cannabis; Chronic; Cognition; Cognitive deficits; Cognitive remediation; Consumption; Data; Elderly; Electrophysiology (science); Exposure to; Functional disorder; Goals; Hippocampus; Human; Impaired cognition; Impairment; Individual; Inflammation; Knowledge; Link; Medial; Mediating; Memory; Modeling; Mus; Nerve Degeneration; Neurobiology; Oral; Pain; Pathology; Performance; Persons; Prefrontal Cortex; Rattus; Recreation; Research; Risk; Route; Shapes; Short-Term Memory; Signal Transduction; Sleeplessness; Smoking; Structure; Synapses; Temporal Lobe; Testing; Tetrahydrocannabinol; adverse outcome; age group; age related; age related neurodegeneration; aged; cannabis administration; executive function; experimental study; inflammatory marker; male; marijuana smoke; marijuana use; marijuana user; middle age; neural; neuroinflammation; neuropathology; novel; pre-clinical research; programs; remediation; sex; spatial memory; tau Proteins; tau aggregation; tau expression; young adult

PROJECT SUMMARY: Older adults are the fastest-growing group of cannabis users in the US. Older adults use cannabis for a variety of reasons, including pain, insomnia, anxiety, and for recreation. Cannabis can, however, also exert robust effects on cognition. Almost all research on cannabis/cannabinoids and cognition has been conducted in young adults, and largely shows that acute administration impairs mnemonic and executive functions mediated by the medial temporal lobe and prefrontal cortex (which are also those most vulnerable to decline in aging and age- related neurodegenerative disease). In contrast, a few studies suggest that cannabinoids can exert distinct effects on the aged compared to the young brain, and preliminary data from our labs show that cannabis can actually enhance cognition selectively in aged rats. Indeed, cannabinoids have been proposed as potential treatments for the age-related neurodegenerative condition Alzheimer's disease (AD), and some preclinical research shows that cannabinoids can attenuate markers linked to AD pathology (e.g., neuroinflammation). Aging studies evaluating cannabis to date, however, are very limited and have not employed either cannabis itself or routes of administration that model those used most frequently by people (smoking and oral consumption). As such, it is unclear how cannabis, as it is actually used, affects cognitive decline and the synaptic dysfunction and AD-like pathology that contribute to cognitive impairments in older subjects. The long-term goal of our program is to determine how cannabis affects cognitive decline in aging and AD, and to determine the mechanisms of such effects. The objective of the current proposal is to model the two most common routes of human cannabis use (smoking and oral consumption) in well-characterized rat models of age-related cognitive decline, and to use these models to begin to elucidate effects of cannabis on behavioral and neurobiological dysfunction associated with aging and AD. Our overarching hypothesis is that cannabis can benefit cognition in aging by attenuating age-associated synaptic dysfunction, neuroinflammation, and tau pathology. Aim 1 will determine how acute cannabis affects performance in young adult and aged rats, as well as the synaptic mechanisms supporting effects of cannabis on cognition in aged subjects. Aim 2 will assess effects of chronic cannabis on cognition in young adult and aged rats, as well as on excitatory/inhibitory signaling and inflammatory markers linked to age-related cognitive impairments. Aim 3 will assess effects of chronic cannabis on AD-like tau pathology and cognition using a novel, targeted AAV-based approach in aged rats. The proposed experiments will be significant because they will provide foundational data concerning whether and how cannabis administration relevant for human consumption yields benefits for age-related cognitive decline and neuropathology.

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