Cocaine and HIV-mediated disruptions of hypothalamic signaling in hypothyroidism

可卡因和艾滋病毒介导的甲状腺功能减退症下丘脑信号传导破坏

基本信息

批准号：
8099600
负责人：
Dianne Teresa LANGFORD
金额：
$ 18.19万
依托单位：
TEMPLE UNIV OF THE COMMONWEALTH
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-07-01 至 2012-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8099600
关键词：
Address Adherence Adult Affect Anti-Retroviral Agents Astrocytes Awareness Back Behavior Behavioral Binding Biological CREB1 gene Cell Line Cell Nucleus Central Nervous System Diseases Cocaine Cocaine Abuse Coculture Techniques Cognition Comorbidity Complication Conflict (Psychology)DARPP Data Dementia Depressed mood Disease Disease Progression Dopamine Receptor Drug Addiction Drug abuse Enzymes Feedback Functional disorder Gene Expression HIV HIV Infections HIV Seropositivity Health Personnel Healthcare Highly Active Antiretroviral Therapy Hormones Human Hypothalamic structure Hypothyroidism Impaired cognition In Vitro Individual Infection Injection of therapeutic agent Investigation Iodide Peroxidase Lead Left Life Link Mediating Mental Depression Molecular Monitor Mood Disorders Mus Neuronal Plasticity Neurons Nuclear Receptors Pathway interactions Patients Pattern Pituitary Gland Plasma Play Process Proteins Quality of life Regulation Research Design Risk Role Signal Transduction Substance abuse problem Synapses Syndrome System Testing Thyroid Diseases Thyroid Gland Thyroid Hormones Thyroxine Treatment Failure Unemployment Virus Withdrawal base cocaine exposure cohort design enzyme activity mouse model neurogranin protein expression public health relevance receptor socioeconomics substance abuser treatment program treatment strategy

项目摘要

DESCRIPTION (provided by applicant): Low socio-economic background, unemployment and depressed environmental surroundings play significant roles in outlook and behavior. Likewise, some individuals suffering from mood disorders may delay seeking healthcare or may not have healthcare benefits and turn to substance abuse (SA) as an alternative. Some comorbidities associated with SA and/or HIV infection directly affect behavior and cognition, and impact significantly on quality of life, adherence to anti-retroviral therapy and successful drug addiction treatment programs. In this context, alterations in thyroid hormone levels have emerged as a complication among some individuals with SA disorders and/or HIV infection, although the molecular basis for the connection is unknown. Our broad hypothesis is that SA and HIV CNS disease contribute to disruptions in the hypothalamic pituitary thyroid (HPT) feedback loop and may lead to or exacerbate hypothyroidism. We propose that these disruptions occur, in part, at the level of hypothalamic signaling and may contribute, in part, to HPT syndrome observed in many individuals who abuse cocaine and are HIV positive. Results from our proposed exploratory study will provide valuable information needed to design more detailed studies addressing: molecular interactions among cocaine, HIV, HAART and CNS HPT signaling impact on cognitive dysfunction, behavior and disease progression treatment strategies for HIV patients with SA disorder at risk for thyroid disease. Our studies are designed to address if cocaine and/or HIV affect pre-existing subclinical or overt hypothyroidism to provide increased awareness among healthcare providers treating substance abuser and/or HIV patients. Left unchecked, the combination of these disorders could lead to increased SA and more rapid disease progression. Results from the proposed studies will increase our understanding of how altered hypothalamic signaling in patients suffering from SA disorders and/or HIV infection may contribute to declining cognition and disease progression, and/or treatment failure. PUBLIC HEALTH RELEVANCE: Alterations in thyroid hormone levels have emerged as a complication among some individuals with SA disorders and/or HIV infection, although the molecular basis for the connection is unknown. Left unchecked, the combination of these disorders could lead to increased SA and more rapid disease progression. Our study will provide information to address molecular interactions among cocaine, HIV, and CNS thyroid signaling.

描述（由申请人提供）：低社会经济背景、失业和抑郁的环境环境在观念和行为中发挥着重要作用。同样，一些患有情绪障碍的人可能会延迟寻求医疗保健，或者可能没有医疗保健福利，而转向药物滥用 (SA) 作为替代方案。一些与 SA 和/或 HIV 感染相关的合并症直接影响行为和认知，并对生活质量、抗逆转录病毒治疗依从性和成功的毒瘾治疗计划产生重大影响。在这种情况下，甲状腺激素水平的改变已成为一些患有 SA 疾病和/或 HIV 感染的个体的并发症，尽管这种联系的分子基础尚不清楚。我们的广泛假设是，SA 和 HIV 中枢神经系统疾病会导致下丘脑垂体甲状腺 (HPT) 反馈回路中断，并可能导致或加剧甲状腺功能减退症。我们认为，这些干扰部分发生在下丘脑信号传导水平，并且可能部分导致在许多滥用可卡因且艾滋病毒呈阳性的个体中观察到的 HPT 综合征。我们提出的探索性研究的结果将提供设计更详细的研究所需的有价值的信息，解决以下问题：可卡因、HIV、HAART 和 CNS HPT 信号传导之间的分子相互作用对认知功能障碍、行为和疾病进展的影响患有甲状腺疾病风险的 SA 疾病 HIV 患者的治疗策略。我们的研究旨在解决可卡因和/或艾滋病毒是否影响先前存在的亚临床或明显的症状甲状腺功能减退症，以提高治疗药物滥用者和/或艾滋病毒患者的医疗保健提供者的认识。如果不加以控制，这些疾病的组合可能会导致 SA 增加和疾病进展更快。拟议研究的结果将加深我们对 SA 疾病和/或 HIV 感染患者下丘脑信号传导改变如何导致认知能力下降和疾病进展和/或治疗失败的理解。公共卫生相关性：甲状腺激素水平的变化已成为一些 SA 疾病和/或 HIV 感染患者的并发症，尽管这种联系的分子基础尚不清楚。如果不加以控制，这些疾病的组合可能会导致 SA 增加和疾病进展更快。我们的研究将提供信息来解决可卡因、艾滋病毒和中枢神经系统甲状腺信号传导之间的分子相互作用。