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博士的研究职业集中于精神分裂症的神经生物学，这是一个主要原因 退伍军人的残疾。这项研究的大部分都集中在低级感觉处理缺陷上 海马多动症，现在被认为是疾病的核心特征。除了工作 检查各种环境，在精神分裂症中观察到海马过度活跃，特雷格拉斯博士 已经探索了这项活动对其他认知过程的影响，并积极从事治疗 发展。最初与烟碱激动剂一起，现在采用其他潜在的治疗策略，是 主要努力以海马过度行动为例，以改善治疗症状的方法 精神分裂症。 Tregellas博士在他目前的项目中确定了低锁定Levetiracetam是否 通常用于控制癫痫发作的抗惊厥药物可能会减少患者的海马多动症。 最初，这种策略不仅是由于有效减少神经元的事实而激发了这种策略 癫痫的兴奋性，但也显示出低剂量的药物可降低神经元活性 患有轻度认知障碍的个体，他们在海马中也表现出过度活性。后 初步研究表明，该药物在小鼠模型中降低了神经元令人兴奋的度量 精神分裂症，特雷格拉斯博士现在处于人类临床试验的初始阶段，以确定是否是否 Levetiracetam可以减少海马过度动力，并改善退伍军人的认知 精神分裂症。目前，这项工作由VA功绩审查奖和VA研究职业提供资金 科学家奖。 除了研究精神分裂症的神经生物学外，特雷格拉斯博士还对 了解当前的精神分裂症治疗如何导致体重增加和代谢问题 患者。为此，他有一个NIH R01来研究抗精神病药诱导的神经元过程 体重增加，并检查运动对患者这些过程的影响。具体来说，这项研究 检查与高体重增加风险相关的抗精神病药的神经元作用 与体重增加的低风险相关的治疗。再加上这一点，Tregellas博士也正在研究 12周运动干预对与食物摄入行为相关的神经元反应的影响。 与这项工作有关，特雷格拉斯博士也有兴趣了解肥胖的神经生物学 一般人口。 Tregellas博士与他的VA合作者Marc Cornier博士一起表演和出版了 一系列研究，研究了俯卧或抗肥胖的个体中神经元反应差异的研究。 这些研究中的许多研究都检查了对能量摄入或支出变化的反应。在他的 当前关于此主题的工作，特雷格拉斯博士正在利用他的精神分裂症工作的观察，这是一个 Alpha-7烟碱激动剂会导致他所拥有的某些网络中的神经元反应降低 先前发现在肥胖个体中过度活跃。这一发现，以及观察到的效果 精神分裂症工作中体重的药物，导致了NIH R01资助的alpha-7的影响 关于普通人群中与肥胖有关的神经生物学和行为过程的烟碱激动剂。 这项工作的目的是更好地了解肥胖和发育治疗的神经生物学以减少 它的普遍性是对VA至关重要的目标。