Stress and obesity synergize to impair neurobehavioral development in females

压力和肥胖协同损害女性神经行为发育

基本信息

批准号：
8870400
负责人：
MAR M SANCHEZ
金额：
$ 69.93万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-07-10 至 2016-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8870400
关键词：
Address Adolescent Adult Adverse effects Affect Amygdaloid structure Animal Feed Animals Anti-Inflammatory Agents Anti-inflammatory Anxiety Awareness Behavior Behavior assessment Behavioral Biological Biological Neural Networks Birth Body fat Brain Child Child health care Childhood Chronic Clinical Cognition Cognitive Consumption Data Development Diet Diffusion Magnetic Resonance Imaging Disease Emotional Emotional Stress Emotions Environment Environmental Risk Factor Estradiol Exposure to Fatty acid glycerol esters Female Fostering Fright Functional Magnetic Resonance Imaging Health Health behavior Hormones Housing Hydrocortisone Impaired cognition Impairment Inflammatory Informal Social Control Intervention Longitudinal Studies Macaca mulatta Mediating Mediation Metabolic Modeling Monkeys Mothers Motivation Obesity Outcome Overweight Pathway interactions Peripheral Phenotype Prefrontal Cortex Pregnancy Process Prospective Studies Protocols documentation Puberty Reporting Rest Risk Risk Factors Sensory Process Shapes Signal Transduction Social Behavior Social Policies Stress Structure Testing adverse outcome anxious behavioral impairment cognitive function cytokine emotional behavior executive function experience girls infancy inflammatory marker innovation maternal stress neurobehavioral neurodevelopment neuroimaging obesity in children offspring postnatal prenatal prenatal stress social social stigma social stress stressor

项目摘要

DESCRIPTION (provided by applicant): Studies of both animals and children show that postnatal stress may have lasting effects on brain structure and function, resulting in behavioral and cognitive impairments, particularly for females. It is also unclear how social stress experienced by the mother during gestation synergizes with postnatal stress experienced by her offspring to produce these phenotypes. Importantly, other environmental factors that may interact with stressor exposure to affect brain development during childhood are frequently overlooked, most notably the consumption of calorically dense diets (CDDs) and the resulting metabolic phenotype. Indeed, there is likely a synergy, as chronic social stress is a cumulative risk factor for childhood obesity. Not only may obesity accelerate the tempo of puberty but limited data in children suggest the developing brain is vulnerable to these metabolic insults, as increased body fat is associated with altered brain structure and deficits in cognition and emotional processing. Understanding the impact of stress and obesity on neurodevelopment is critically relevant, given alarming rates of obesity in children, likely due to the consumption of CDDs - a dietary environment quite unlike the typical low caloric diets fed animals used as models for children. Key biological signals could be stress-induced elevations in cortisol and proinflammatory cytokines that are exacerbated by increased fat mass. Prospective studies of the developmental origins of health and disease are difficult to do in children. However, socially housed rhesus monkeys provide an effective translational model, as social subordination produces distinct stress-related phenotypes even during development. This application will address four specific aims to test the overarching hypothesis that prenatal maternal stress interacts with post natal social stress to alter female neurobehavioral development from infancy through puberty and these impairments are exacerbated by obesity. Aim 1 will determine whether increased fat mass interacts with postnatal social stress to alter developmental trajectories of female social and emotional behavior, as well as prefrontal-related cognitive function. Using neuroimaging, Aim 2 will test the hypothesis that social stress and increased fat mass will synergize to alter structural and functional development of the prefrontal cortex (PFC) and its connectivity with regions regulating social and emotional behaviors as well as executive function and self-regulation from infancy, with differences accelerating through the pubertal transition. Mediation analysis in Aim 3 will examine whether cortisol and inflammatory markers mediate the effects of social stress and fat mass on impaired neurobehavioral development. Using cross-fostering, Aim 4 will determine how maternal stress during gestation synergizes with postnatal social stress and obesity to further compromise neurobehavioral development. The project will identify potential biological signals that mediate the adverse effects of stress ad obesity on brain health and behavior and, in doing so, will provide crucial information that will help shape clinical interventions and social policy improvement to optimize neurobehavioral development in girls.

描述（由申请人提供）：对动物和儿童的研究表明，产后压力可能会对大脑结构和功能产生持久影响，从而导致行为和认知障碍，尤其是女性。尚不清楚母亲在妊娠期间的社会压力如何与后代在产生这些表型的产后压力协同作用。重要的是，可能会忽略与压力源相互作用以影响大脑发育的其他环境因素经常被忽略，最值得注意的是，热量致密饮食（CDD）和由此产生的代谢表型。确实，可能是一种协同作用，因为慢性社会压力是儿童肥胖症的累积危险因素。肥胖不仅可以加快青春期的节奏，而且儿童的数据有限，这表明发育中的大脑容易受到这些代谢侮辱的影响，因为增加的体内脂肪与大脑结构的改变以及认知和情感处理的不足有关。鉴于儿童的肥胖率令人震惊，了解压力和肥胖对神经发育的影响至关重要，这可能是由于食用CDD所致 - 饮食环境与喂养用作儿童模型的典型低热量饮食完全不同。关键的生物学信号可能是压力诱导的皮质醇和促炎细胞因子的升高，而脂肪质量增加会加剧。关于儿童健康和疾病的发展起源的前瞻性研究很难做到。然而，社会上的恒河猴提供了一个有效的翻译模型，因为社会从属能够在发展过程中产生与压力相关的独特表型。该应用将解决四个特定的目的，以检验总体假设，即产前孕产妇应与出生后的社会压力相互作用，以改变女性神经行为从婴儿期到青春期的发展，并且这些障碍因肥胖而加剧。 AIM 1将确定增加的脂肪质量是否与产后社会压力相互作用，以改变女性社会和情感行为的发育轨迹以及与前额叶相关的认知功能。使用神经影像学，AIM 2将检验以下假设：社会压力和增加的脂肪质量将协同作用，以改变前额叶皮层（PFC）的结构和功能发展及其与调节社会和情绪行为的区域的连通性以及执行功能以及婴儿期的自我调控，并从婴儿期间通过差异来加速差异。 AIM 3中的调解分析将检查皮质醇和炎症标志物是否介导社会压力和脂肪量对神经行为发育受损的影响。 AIM 4使用交叉促进，将确定妊娠期间的母体压力如何与产后社会压力和肥胖相协同，以进一步损害神经行为的发展。该项目将确定潜在的生物学信号，这些信号介导压力肥胖对脑健康和行为的不利影响，并在此过程中提供重要的信息，这将有助于塑造临床干预措施和社会政策改善，以优化女孩的神经行为发展。