CSR&D Research Career Scientist Award Application

企业社会责任

• 批准号: 10426078
• 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/10426078
• 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; Dose; Eating; Energy Intake; Energy Metabolism; Epilepsy; Exercise; Functional disorder; Funding; General Population; Goals; Grant; Health; Healthcare; Hippocampus (Brain); 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; Pharmacology; Prevalence; Process; Psychiatry; Publications; Publishing; Quality of life; Radio; Reducing Agents; Research; Resistance; Rest; Risk; Schizophrenia; Science; Scientist; Seizures; Sensory; Series; Societies; Sum; 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; 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博士的研究生涯一直专注于精神分裂症的神经生物学， 残疾退伍军人。大部分研究都集中在低水平的感觉处理缺陷， 海马过度活跃，现在被认为是这种疾病的核心特征。除了工作 Tregellas博士研究了在精神分裂症中观察到的海马体过度活跃的各种情况， 已经探索了这种活动对其他认知过程的影响，并积极参与治疗 发展最初使用烟碱激动剂，现在使用其他潜在的治疗策略， 领导努力以海马过度活跃为目标，作为改善治疗症状的手段， 精神分裂症在他目前的项目中，Tregellas博士正在确定低损失的左乙拉西坦， 通常用于控制癫痫发作的抗惊厥药，可降低患者的海马活动过度。 这种策略最初的动机不仅是左乙拉西坦有效地减少神经元的 此外，低剂量的药物也显示出降低癫痫患者的神经元活动， 有轻度认知障碍的人，他们也表现出海马体的过度活动。后 最初的研究表明，该试剂降低了小鼠模型中神经元兴奋性的测量， Tregellas博士目前正处于人类临床试验的初始阶段，以确定是否 左乙拉西坦可以减少海马活动过度，改善退伍军人的认知能力。 精神分裂症这项工作目前由VA Merit Review Award和VA Research Career资助。 科学家奖。 除了研究精神分裂症的神经生物学外，Tregellas博士还对以下方面感兴趣： 了解目前精神分裂症的治疗如何导致体重增加和代谢问题， 患者为此，他有一个NIH R 01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 研究了抗精神病药物与体重增加高风险相关的神经元效应， 与体重增加风险低相关的治疗。与此同时，Tregellas博士也在研究 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。 与这项工作相关的是，Tregellas博士也对了解肥胖的神经生物学感兴趣， 一般人口。Tregellas博士与他的退伍军人事务部合作者Marc科尼尔博士合作， 一系列的研究检查了易患或不易患肥胖症的个体的神经元反应的差异。 其中许多研究检查了对能量摄入或支出变化的反应。在他 Tregellas博士正在利用他的精神分裂症工作中的观察结果， α-7烟碱激动剂导致一些相同的网络中的神经元反应降低， 以前发现在肥胖症患者中过度活跃。这一发现，沿着观察到的影响， 在精神分裂症的工作中，药物对体重的影响，导致了一项由NIH R 01资助的关于α-7的影响的研究。 烟碱激动剂对一般人群中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，以减少 它的流行，一个对VA至关重要的目标。