Effects of Prenatal Alcohol Exposure on the Neurobiology of Social Behavior

产前酒精暴露对社会行为神经生物学的影响

• 批准号: 8785841
• 负责人: Parker James Holman
• 金额: $ 2.25万
• 依托单位: UNIVERSITY OF BRITISH COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8785841
• 关键词: Acute; Adolescence; Adolescent Development; Adrenal Glands; Adult; Affect; Age; Amygdaloid structure; Animal Model; Animals; Area; Behavioral; Brain; Caspase-1; Characteristics; Childhood; Clinical; Clinical Research; Cognitive; Communities; Complex; Corticosterone; Development; Diagnosis; Disease; Early Diagnosis; Enzyme-Linked Immunosorbent Assay; Estradiol; FOS gene; Female; Fetal Alcohol Exposure; Fetal Alcohol Spectrum Disorder; Frontotemporal Dementia; Functional disorder; General Population; Gonadal Steroid Hormones; High Prevalence; Hormones; Hypothalamic structure; Impairment; Individual; Injection of therapeutic agent; Intervention; Laws; Lead; Learning; Link; Literature; MAPK14 gene; Measurement; Mediating; Mental Health; Modeling; Neurobiology; Neurologic; Neuropeptides; Neurotransmitters; Oxytocin; Oxytocin Receptor; Pattern; Peptides; Peripheral; Physiological; Pituitary Gland; Plasma; Predictive Value; Prefrontal Cortex; Puberty; Radioimmunoassay; Rattus; Regulation; Research Proposals; Role; Saline; Schizophrenia; Schools; Social Behavior; Social Discrimination; Social Environment; Social Interaction; Stress; Structure of terminal stria nuclei of preoptic region; System; Testing; Testosterone; United States; Vasopressin Receptor; Vasopressins; Work; alcohol consumption during pregnancy; attenuation; autism spectrum disorder; behavior test; behavioral impairment; biological adaptation to stress; critical developmental period; critical period; insight; male; memory recognition; neurobehavioral; pre-clinical; public health relevance; receptor; receptor binding; relating to nervous system; social

DESCRIPTION (provided by applicant): Fetal Alcohol Spectrum Disorder (FASD) is an umbrella term that refers to the continuum of neurobehavioral and physiological impairments resulting from maternal alcohol consumption during pregnancy. Of the cognitive, physiological and behavioral impairments associated with prenatal alcohol exposure (PAE) documented in the clinical and pre-clinical literature, lifelong social behavior deficits serve as a unifying feaure across the entire continuum of Fetal Alcohol Spectrum Disorders (FASD). Impaired social behavior in individuals with FASD has widespread implications for other domains and may contribute to difficulties within the school environment, social rejection, trouble with the law, ad later mental health problems. PAE-related social behavior deficits emerge early in development and become more pronounced prior to and during adolescence, a critical period of development during which significant behavioral, cognitive, and physiological changes occur, including onset of puberty, making adolescence a unique period of increased vulnerability to social behavior dysfunction. However, because of the considerable overlap in the characteristics of FASD and other childhood disorders with social behavior impairments - including autism spectrum disorder (ASD) - reaching a definitive diagnosis presents a challenge for the clinical community. Indeed, it has been suggested that the difficulty in identifying individuals affected by FASD has led to an underestimation of its already high prevalence (2-5%) in the general population. The relevance of the current research proposal relies on the need for establishing a more specific social neurobehavioral profile that could support the development of specific strategies for earlier diagnoses and more targeted interventions for FASD. Previous pre-clinical and clinical research suggests that PAE affects brain areas and alters neurotransmitters shown to support social behavior, including the prefrontal cortex, amygdala, and hypothalamus, as well as the oxytocin and vasopressin neurotransmitter systems. Accordingly, the present proposal will characterize social behavior and its underlying neural correlates using a well-established animal model of moderate PAE. We will test the hypothesis that PAE results in social behavior impairments (Aim 1) that result from altered development of the OT/AVP systems (Aim 2). In addition, because the clinical and preclinical literature support a role for oxytocin treatment in enhancing aspects of social behavior in healthy individuals as well as in ameliorating social behavior deficits associated with ASD, frontotemporal dementia, and schizophrenia, we also propose to investigate oxytocin administration as an intervention for rescuing social behavior deficits following PAE (Aim 3). The proposed studies will provide further insight into mechanisms underlying the effects of PAE on social behavior, and suggest possible approaches for attenuation of such deficits.

描述（由申请人提供）：胎儿酒精谱系障碍（FASD）是一个总称，指的是母亲在怀孕期间饮酒导致的神经行为和生理损伤的连续性。在临床和临床前文献中记录的与产前酒精暴露（PAE）相关的认知、生理和行为障碍中，终身社会行为缺陷是胎儿酒精谱系障碍（FASD）整个连续体的统一特征。FASD患者的社会行为受损对其他领域也有广泛的影响，可能导致他们在学校环境中遇到困难、被社会排斥、违反法律，以及后来的精神健康问题。与pae相关的社会行为缺陷在发育早期出现，并在青春期之前和青春期期间变得更加明显，青春期是发育的关键时期，在此期间发生了重大的行为、认知和生理变化，包括青春期的开始，使青春期成为一个独特的易受社会行为功能障碍影响的时期。然而，由于FASD和其他具有社会行为障碍的儿童疾病（包括自闭症谱系障碍（ASD））的特征有相当大的重叠，对临床社区来说，要做出明确的诊断是一个挑战。事实上，有人认为，识别受FASD影响的个体的困难导致了一个