CSR&D Research Career Scientist Award Application

企业社会责任

• 批准号: 10657428
• 负责人: JASON R TREGELLAS
• 金额: --
• 依托单位: VA EASTERN COLORADO HEALTH CARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10657428
• 关键词: Affinity; American; Anticonvulsants; Antipsychotic Agents; Attention; Award; Behavior; Behavioral; Biological Psychiatry; Brain; Brain imaging; Cardiovascular Diseases; Cause of Death; Clinical Nutrition; Clinical Trials; Cognition; Congresses; Coupled; Dedications; Dose; Eating; Energy Intake; Energy Metabolism; Epilepsy; Exercise; Functional disorder; Funding; General Population; Goals; Grant; Health; Healthcare; Hippocampus; Human; Hyperactivity; Impaired cognition; Individual; International; Interview; Journals; Levetiracetam; Life; Magnetic Resonance Imaging; Manuscripts; Measures; Medical center; Mental disorders; Metabolic; Neurobiology; Neurons; Neurosciences; Nicotinic Agonists; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Paper; Pathology; Patients; Peer Review; Pharmaceutical Preparations; Prevalence; Process; Productivity; Psychiatry; Publications; Publishing; Quality of life; Radio; Reducing Agents; Research; Resistance; Rest; Risk; Schizophrenia; Science; Scientist; Seizures; Sensory; Series; Societies; Symptoms; Therapeutic; United States National Institutes of Health; Veterans; Washington; Weight; Weight Gain; Work; brain research; cardiometabolism; career; cognitive process; college; disability; effective therapy; exercise intervention; high risk; imaging facilities; improved; instrumentation; interest; meetings; mild cognitive impairment; mortality; mouse model; neuroimaging; neuronal excitability; neuropsychopharmacology; obesity prevention; pharmacologic; response; symposium; symptom treatment; therapeutic development; therapy development; trend

Dr. Tregellas’ research career has focused on the neurobiology of schizophrenia, a leading cause of disability for Veterans. Much of this research is focused on low-level sensory processing deficits and hippocampal hyperactivity, which is now considered a core feature of the illness. In addition to work examining various contexts in which hippocampal hyperactivity is observed in schizophrenia, Dr. Tregellas has explored the effect of this activity on other cognitive processes and is actively engaged in therapeutic development. Initially with nicotinic agonists, and now with other potential therapeutic strategies, he is leading efforts to target hippocampal hyperactivity as a means to improve treatments for the symptoms of schizophrenia. In his current project, Dr. Tregellas is determining if low-lose levetiracetam, an anticonvulsant agent typically used to control seizures, may reduce hippocampal hyperactivity in patients. This strategy originally was motivated not only by the fact that levetiracetam effectively reduces neuronal excitability in epilepsy, but also that low doses of the agent were shown to reduce neuronal activity in individuals with mild cognitive impairment, who also show excessive activity in the hippocampus. After initial studies showing that the agent reduces a measure of neuronal excitability in a mouse model of schizophrenia, Dr. Tregellas is now in the initial stages of a human clinical trial to determine if levetiracetam can reduce hippocampal hyperactivity and improve cognition in Veterans with schizophrenia. This work is currently funded by a VA Merit Review Award and a VA Research Career Scientist Award. In addition to work examining the neurobiology of schizophrenia, Dr. Tregellas is also interested in understanding how current treatments for schizophrenia cause weight gain and metabolic problems in patients. Toward this end, he has an NIH R01 to study the neuronal processes of antipsychotic-induced weight gain, and to examine the effects of exercise on these processes in patients. Specifically, this study examines the neuronal effects of antipsychotics associated with a high risk of weight gain, compared to treatments associated with a low risk of weight gain. Coupled with this, Dr. Tregellas also is studying the effects of a 12-week exercise intervention on neuronal responses associated with food intake behavior. Related to this work, Dr. Tregellas also is interested in understanding the neurobiology of obesity in the general population. With his VA collaborator Dr. Marc Cornier, Dr. Tregellas has performed and published a series of studies examining differences in neuronal response in individuals prone or resistant to obesity. Many of these studies have examined responses to changes in energy intake or expenditure. In his current work on this topic, Dr. Tregellas is leveraging an observation from his schizophrenia work, that an alpha-7 nicotinic agonist causes reduced neuronal response in some of the same networks that he had previously found to be hyperactive in individuals with obesity. This finding, along with an observed effect of drug on weight in the schizophrenia work, led to an NIH R01-funded study of the effects of an alpha-7 nicotinic agonist on neurobiological and behavioral processes related to obesity in the general population. The aim of this work is to better understand the neurobiology of obesity and develop treatments to reduce its prevalence, a goal of vital importance to the VA.

Tregellas 博士的研究生涯主要集中在精神分裂症的神经生物学上，这是导致精神分裂症的主要原因 这项研究的大部分内容都集中在低水平的感觉处理缺陷和 海马过度活跃，现在被认为是除了工作之外的疾病的核心特征。 Tregellas 博士检查了精神分裂症患者海马过度活跃的各种情况 探索了这项活动对其他认知过程的影响，并积极参与治疗 他最初使用烟碱激动剂，现在使用其他潜在的治疗策略。 领导针对海马过度活跃的努力，以此作为改善海马症状治疗的手段 在他当前的项目中，Tregellas 博士正在确定低剂量左乙拉西坦是否是一种治疗精神分裂症的药物。 抗惊厥药通常用于控制癫痫发作，可以减少患者海马的过度活跃。 这一策略最初的动机不仅是因为左乙拉西坦有效地减少了神经元 癫痫的兴奋性，而且低剂量的药物也被证明可以减少神经元活动 患有轻度认知障碍的人，也表现出海马体过度活动。 初步研究表明，该药物降低了小鼠模型中神经兴奋性的测量值 Tregellas 博士目前正处于一项人体临床试验的初始阶段，以确定是否患有精神分裂症 左乙拉西坦可以减少海马过度活跃并改善退伍军人的认知 这项工作目前由 VA 优异评审奖和 VA 研究事业资助。 科学家奖。 除了研究精神分裂症的神经生物学之外，Tregellas 博士还对 了解当前的精神分裂症治疗方法如何导致体重增加和代谢问题 为此，他拥有 NIH R01 来研究抗精神病药物引起的神经元过程。 体重增加，并检查运动对患者这些过程的影响。 检查与体重增加高风险相关的抗精神病药物的神经效应，与 与此同时，Tregellas 博士还在研究与体重增加风险较低相关的治疗方法。 12 周的运动干预对与食物摄入行为相关的神经反应的影响。 与这项工作相关，Tregellas 博士还对了解肥胖的神经生物学感兴趣。 Tregellas 博士与他的 VA 合作者 Marc Cornier 博士一起表演并发表了论文。 一系列研究检查易肥胖或抗肥胖个体的神经反应差异。 其中许多研究考察了对能量摄入或支出变化的反应。 Tregellas 博士正在利用他在精神分裂症研究中的观察结果，即 α-7 烟碱激动剂导致某些与他相同的网络中的神经反应减弱 先前发现肥胖个体过度活跃这一发现以及观察到的效果。 在精神分裂症研究中药物对体重的影响，导致了 NIH R01 资助的一项关于 alpha-7 影响的研究 烟碱激动剂对普通人群与肥胖相关的神经生物学和行为过程的影响。 这项工作的目的是更好地了解肥胖的神经生物学并开发治疗方法来减少肥胖 其普及率是退伍军人事务部至关重要的目标。