Fatty Acids and Preclinical Models of Psychiatric Disorders

脂肪酸和精神疾病的临床前模型

• 批准号: 8429361
• 负责人: BITA MOGHADDAM
• 金额: $ 21.67万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-02-16 至 2015-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8429361
• 关键词: Accounting; Address; Adolescence; Adolescent; Affect; Affective; Animal Model; Animals; Archives; Attention deficit hyperactivity disorder; Behavior; Behavioral; Brain; Brain region; Categories; Cereals; Clinical; Cognitive; Cognitive deficits; Complex; Consumption; Controlled Clinical Trials; Corn Oil; Corpus striatum structure; Cues; Data; Development; Diet; Dietary intake; Disease; Double-Blind Method; Employee Strikes; Event; Extinction (Psychology); Face; Fatty Acids; Fatty acid glycerol esters; Future; Generations; Human; Individual; Intake; Intervention; Investigation; Learning; Link; Literature; Livestock; Maintenance; Malnutrition; Margarine; Mediating; Mental Health; Mental disorders; Methodology; Modeling; Molecular; Mood Disorders; Motivation; N-3 polyunsaturated fatty acid; Neurons; Neurosciences; Omega-3 Fatty Acids; Operant Conditioning; Outcome; Outcome Measure; Outcome Study; Parents; Placebo Control; Pre-Clinical Model; Prefrontal Cortex; Process; Psychiatry; Psychological reinforcement; Psychopathology; Psychotic Disorders; Public Health; Publishing; Randomized; Rattus; Reporting; Research; Retrieval; Rewards; Rodent Model; Schizophrenia; Staging; Supplementation; Testing; Ventral Striatum; behavior influence; behavioral impairment; depressive symptoms; dietary supplements; falls; fatty acid metabolism; feeding; high risk; indexing; innovation; man; motivated behavior; placebo controlled study; premature; research study; response; trend

DESCRIPTION (provided by applicant): Deficiency in dietary intake of omega-3 polyunsaturated fatty acids (n-3 PUFA) negatively impacts cognitive and affective functioning. A plethora of psychopathology literature also implicates n-3 PUFA deficiency in psychiatric disorders, including mood disorders and schizophrenia. Thus, defining potential neuronal mechanisms that link n-3 PUFA levels to behavioral deficits has important implications for basic neuroscience, as well as for public health, given that the trend of the modern diet has been toward reduced n-3 PUFA intake. The overarching objective of this exploratory R21 application is to move a field, which is becoming increasingly relevant to mental health, forward from the phenomenological stage to delineating brain mechanisms. We propose to use a rodent model to gain mechanistic understanding of the impact of n-3 PUFA deficiency and supplementation on coordinated neuronal activity of the prefrontal cortex (PFC) and ventral striatum (vStr) of adolescent rats. We have found subtle behavioral impairments in n-3 PUFA deficient adolescent rats, suggestive of disrupted motivational and attentional processing. Electrophysiological recordings of single unit activity and local field potentials (LFPs) in PFC subregions and vStr of behaviorally engaged adolescent rats will be made during a reward driven learning task to address two hypotheses: (1) n-3 PUFA deficiency disrupts the dynamics of neuronal activity in the PFC and ventral striatum in response to salient task relevant events, (2) These cellular disruptions are ameliorated with n-3 PUFA supplementation. It is anticipated that the results of these studies will increase our mechanistic understanding of the functional circuitry that influences the behavioral effects of n-3 PUFA deficiency and supplementation.

描述（由申请人提供）：ω-3多不饱和脂肪酸（n-3 PUFA）饮食摄入不足对认知和情感功能产生负面影响。大量的精神病理学文献也暗示精神疾病，包括情绪障碍和精神分裂症中的n-3 PUFA缺乏。因此，鉴于现代饮食的趋势是减少n-3 PUFA摄入量，定义将n-3 PUFA水平与行为缺陷联系起来的潜在神经元机制对基础神经科学和公共卫生具有重要影响。这个探索性的R21应用程序的首要目标是移动一个领域，这是越来越相关的心理健康，从现象学阶段描绘大脑机制前进。我们建议使用啮齿动物模型，以获得机制的理解n-3多不饱和脂肪酸缺乏和补充协调的前额叶皮层（PFC）和腹侧纹状体（vStr）的青春期大鼠的神经元活动的影响。我们发现n-3多不饱和脂肪酸缺乏的青春期大鼠存在细微的行为障碍，这表明动机和注意力处理受到干扰。在奖励驱动的学习任务期间，将对行为参与的青春期大鼠的PFC子区域和vStr中的单个单位活动和局部场电位（LFP）进行电生理记录，以解决两个假设：（1）n-3 PUFA缺乏破坏PFC和腹侧纹状体中响应于显著任务相关事件的神经元活动的动力学，（2）补充n-3 PUFA可改善这些细胞破坏。预计这些研究的结果将增加我们对影响n-3 PUFA缺乏和补充的行为效应的功能电路的机械理解。

项目成果

Adolescent behavior and dopamine availability are uniquely sensitive to dietary omega-3 fatty acid deficiency.

• DOI: 10.1016/j.biopsych.2013.06.007
• 发表时间: 2014-01-01
• 期刊: BIOLOGICAL PSYCHIATRY
• 影响因子: 10.6
• 作者: Bondi, Corina O.;Taha, Ameer Y.;Tock, Jody L.;Totah, Nelson K. B.;Cheon, Yewon;Torres, Gonzalo E.;Rapoport, Stanley I.;Moghaddam, Bita
• 通讯作者: Moghaddam, Bita