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
基本信息
- 批准号:10469575
- 负责人:
- 金额:$ 60.44万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 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:
- 关键词:AcuteAddressAffectAgeAge-associated memory impairmentAgingAgitationAlzheimer like pathologyAlzheimer&aposs DiseaseAlzheimer&aposs disease pathologyAnxietyAttenuatedBehavioralBehavioral SymptomsBiochemicalBrainCannabinoidsCannabisChronicCognitionCognitiveCognitive deficitsConsumptionDataElderlyElectrophysiology (science)Exposure toFoundationsFunctional disorderGoalsHippocampus (Brain)HumanImpaired cognitionImpairmentIndividualInflammationKnowledgeLinkMedialMediatingMemoryModelingMusNerve DegenerationNeurobiologyOralPainPathologyPerformancePersonsPrefrontal CortexRattusRecreationResearchRiskRouteShapesShort-Term MemorySignal TransductionSleeplessnessSmokingStructureSynapsesTemporal LobeTestingTetrahydrocannabinoladverse outcomeage groupage relatedage related neurodegenerationagedbaseexecutive functionexperimental studyinflammatory markermalemarijuana smokemarijuana usemarijuana userneuroinflammationneuropathologynovelpre-clinical researchprogramsrelating to nervous systemsexspatial memorytau Proteinstau aggregationtau expressionyoung adult
项目摘要
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.
项目概要:
老年人是美国增长最快的大麻使用者群体。老年人使用大麻的各种
原因包括疼痛、失眠、焦虑和娱乐。然而,大麻也可以发挥强大的作用,
对认知的影响几乎所有关于大麻/大麻素和认知的研究都是在年轻人中进行的。
成人,并在很大程度上表明,急性管理损害记忆和执行功能介导的
内侧颞叶和前额叶皮层(也是最容易衰老和衰老的部位,
相关的神经退行性疾病)。相反,一些研究表明,大麻素可以发挥独特的作用,
与年轻人的大脑相比,大麻对老年人的影响,我们实验室的初步数据表明,大麻可以
实际上可以选择性地增强老年大鼠的认知能力。事实上,大麻素被认为是潜在的
治疗与年龄相关的神经退行性疾病阿尔茨海默病(AD),以及一些临床前
研究表明大麻素可以减弱与AD病理学相关的标志物(例如,神经炎症)。
然而,迄今为止评估大麻的老化研究非常有限,并且没有使用任何大麻
其本身或给药途径,模拟人们最常用的给药途径(吸烟和口服
消费)。因此,目前还不清楚大麻实际上是如何影响认知能力下降和
突触功能障碍和AD样病理,导致老年受试者的认知障碍。
我们项目的长期目标是确定大麻如何影响衰老和AD的认知能力下降,
并确定这种影响的机制。本提案的目标是建立这两个模型,
在充分表征的大鼠模型中,人类使用大麻的最常见途径(吸烟和口服)
与年龄相关的认知能力下降,并使用这些模型开始阐明大麻对行为的影响
以及与衰老和AD相关的神经生物学功能障碍。我们的首要假设是大麻
通过减弱与年龄相关的突触功能障碍、神经炎症和tau蛋白,
病理目标1将确定急性大麻如何影响年轻成年和老年大鼠的表现,以及
作为支持大麻对老年受试者认知影响的突触机制。目标2将评估
慢性大麻对年轻成年和老年大鼠认知功能以及兴奋/抑制信号传导的影响
以及与年龄相关的认知障碍相关的炎症标志物。目标3将评估慢性
大麻对AD样tau病理学和认知的影响,使用一种新的,有针对性的基于AAV的方法在老年大鼠中进行。的
拟议的实验将是重要的,因为它们将提供有关是否和
与人类消费相关的大麻管理如何对与年龄相关的认知下降产生益处
和神经病理学
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
JENNIFER Lynn BIZON其他文献
JENNIFER Lynn BIZON的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('JENNIFER Lynn BIZON', 18)}}的其他基金
Mechanisms and therapeutic potential of vagus nerve stimulation in aging and Alzheimer’s disease
迷走神经刺激在衰老和阿尔茨海默病中的机制和治疗潜力
- 批准号:
10209090 - 财政年份:2021
- 资助金额:
$ 60.44万 - 项目类别:
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:
10316617 - 财政年份:2021
- 资助金额:
$ 60.44万 - 项目类别:
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 - 财政年份:2021
- 资助金额:
$ 60.44万 - 项目类别:
Immunotherapy targeting the HPA axis in Alzheimer's disease
针对阿尔茨海默病 HPA 轴的免疫疗法
- 批准号:
10846355 - 财政年份:2019
- 资助金额:
$ 60.44万 - 项目类别:
Clinical and Translational Pre-doctoral training in Alzheimer's Disease and Related Dementias
阿尔茨海默病和相关痴呆症的临床和转化博士前培训
- 批准号:
10475693 - 财政年份:2018
- 资助金额:
$ 60.44万 - 项目类别:
Clinical and Translational Pre-doctoral training in Alzheimer's Disease and Related Dementias
阿尔茨海默病和相关痴呆症的临床和转化博士前培训
- 批准号:
10228736 - 财政年份:2018
- 资助金额:
$ 60.44万 - 项目类别:
2RO1AG029421 Neural Mechanisms of Age-related cognitive decline
2RO1AG029421 与年龄相关的认知能力下降的神经机制
- 批准号:
8852384 - 财政年份:2014
- 资助金额:
$ 60.44万 - 项目类别:
Neural Mechanisms of Cognitive Decline in Aging
衰老过程中认知能力下降的神经机制
- 批准号:
9250037 - 财政年份:2007
- 资助金额:
$ 60.44万 - 项目类别:
Basal forebrain and cognitive aging: Novel experimental and theraptutic avenues
基底前脑和认知衰老:新的实验和治疗途径
- 批准号:
8180233 - 财政年份:2007
- 资助金额:
$ 60.44万 - 项目类别:
Basal forebrain and cognitive aging: Novel experimental and theraptutic avenues
基底前脑和认知衰老:新的实验和治疗途径
- 批准号:
7627219 - 财政年份:2007
- 资助金额:
$ 60.44万 - 项目类别:
相似海外基金
Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
- 批准号:
MR/S03398X/2 - 财政年份:2024
- 资助金额:
$ 60.44万 - 项目类别:
Fellowship
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
- 批准号:
EP/Y001486/1 - 财政年份:2024
- 资助金额:
$ 60.44万 - 项目类别:
Research Grant
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
- 批准号:
2338423 - 财政年份:2024
- 资助金额:
$ 60.44万 - 项目类别:
Continuing Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
- 批准号:
MR/X03657X/1 - 财政年份:2024
- 资助金额:
$ 60.44万 - 项目类别:
Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
- 批准号:
2348066 - 财政年份:2024
- 资助金额:
$ 60.44万 - 项目类别:
Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
- 批准号:
AH/Z505481/1 - 财政年份:2024
- 资助金额:
$ 60.44万 - 项目类别:
Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10107647 - 财政年份:2024
- 资助金额:
$ 60.44万 - 项目类别:
EU-Funded
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
- 批准号:
2341402 - 财政年份:2024
- 资助金额:
$ 60.44万 - 项目类别:
Standard Grant
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10106221 - 财政年份:2024
- 资助金额:
$ 60.44万 - 项目类别:
EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
- 批准号:
AH/Z505341/1 - 财政年份:2024
- 资助金额:
$ 60.44万 - 项目类别:
Research Grant