CSR&D Research Career Scientist Award Application

Tregellas博士的研究生涯一直专注于精神分裂症的神经生物学，精神分裂症是导致精神分裂症的主要原因 退伍军人的残疾问题。这项研究的大部分都集中在低水平的感觉加工缺陷和 海马区过度活跃，这现在被认为是这种疾病的核心特征。除了工作之外 特雷盖拉斯博士研究了在精神分裂症中观察到的海马区过度活跃的各种情况 探索了这一活动对其他认知过程的影响，并积极参与治疗 发展。最初使用尼古丁激动剂，现在使用其他潜在的治疗策略，他 领导以海马体多动为目标的努力，以此作为改进对 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是否可以 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区过度活动。 这一策略最初的动机不仅是左乙拉西坦有效地减少了神经元 癫痫的兴奋性，但也表明低剂量的药物减少神经元的活动。 轻度认知障碍的人，他们的海马体也表现出过度活动。之后 初步研究表明，该药物降低了小鼠模型中神经元的兴奋性。 Tregellas博士目前正处于人类临床试验的初始阶段，以确定 左乙拉西坦可减少退伍军人海马区过度活动并改善认知功能 精神分裂症。这项工作目前由退伍军人荣誉奖和退伍军人研究生涯资助 科学家奖。 除了研究精神分裂症的神经生物学，特雷盖拉斯博士还对 了解目前对精神分裂症的治疗如何导致体重增加和代谢问题 病人。为此，他有一台NIH R01来研究抗精神病药物诱导的神经元过程 体重增加，并检查运动对患者这些过程的影响。具体地说，这项研究 检查与体重增加的高风险相关的抗精神病药物的神经元影响，与 与低体重增加风险相关的治疗。此外，特雷盖拉斯博士还在研究 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，特雷格拉斯博士还对了解老年人肥胖的神经生物学感兴趣。 普通人口。Tregellas博士与他的VA合作者Marc Cornier博士一起表演并出版了 一系列研究考察了肥胖倾向或抵抗个体的神经元反应的差异。 这些研究中的许多都考察了对能量摄入或消耗变化的反应。在他的 目前关于这一主题的工作，Tregellas博士利用了他在精神分裂症工作中的观察，即 α-7尼古丁激动剂在一些与他相同的网络中导致神经元反应减弱 以前发现肥胖者有过度活跃的症状。这一发现以及观察到的影响 药物对精神分裂症体重影响的研究，导致了一项由NIH R01资助的关于α-7影响的研究 尼古丁激动剂对普通人群中与肥胖有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，并开发减少肥胖的治疗方法。 它的流行，一个对退伍军人管理局至关重要的目标。

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.