Adolescence, sex and timing of neural vulnerability

青春期、性别和神经脆弱性的时间

• 批准号: 8586360
• 负责人: JANICE M JURASKA
• 金额: $ 18.28万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-12-01 至 2015-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8586360
• 关键词: Adolescence; Adolescent; Adult; Age; Astrocytes; Behavior; Behavioral; Complement 1q; Dendrites; Dendritic Spines; Depressive disorder; Disease; Dissociation; Emotional; Environment; Exploratory/Developmental Grant; Female; Future; Glutamates; Goals; Grant; Growth Factor; Hormones; Human; Incidence; Insulin-Like Growth Factor I; Measures; Mental Depression; Mental disorders; Modeling; Neuroglia; Neurons; Onset of illness; Patients; Pattern; Precipitating Factors; Predisposition; Prefrontal Cortex; Psychopathology; Rattus; Reaction; Role; Sampling; Schizophrenia; Severities; Sex Characteristics; Signaling Molecule; Stress; Swimming; Symptoms; Synapses; System; Testing; Time; Work; addiction; base; hippocampal pyramidal neuron; male; monoamine; preadolescence; prepulse inhibition; public health relevance; receptor; relating to nervous system; restraint stress; sex; young adult

DESCRIPTION (provided by applicant): Adolescence is a unique transitional time, long noted for emotional turmoil, increased vulnerability to addiction and the onset of psychiatric disorders such as depression and schizophrenia. The neural restructuring that occurs at this time may result in increased vulnerability to the environment including stress. The prefrontal cortex of humans, in particular, decreases in size during adolescence with different timing and slope of trajectories in each sex (Lenroot et al, 2007). This means that the cellular basis for the size decrease must also differ between males and females. Pruning of neurons, dendrites, synapses and receptors occurs in the prefrontal cortex during adolescence in humans and other species (Huttenlocher, 1979; Lewis, 1997; Andersen et al, 2000; Markham et al, 2007), and there are indications of sex differences in pruning in the rare instances where they have been examined. The timing of pruning will be investigated here in Aim 1, and the implications of sex differences in this timing will be tested with stress in Aim 2. Stress during human adolescence is a known predisposition for psychopathology and can precipitate symptoms (Grant et al, 2004; Arnsten, 2011) which indicates a disruption of normal pruning. There are sex differences in the behavioral reaction to stress in adolescents (Romeo; 2010; Wilkin et al, 2012). This may contribute to the incidence and severity of schizophrenia during adolescent onset (1.4:1 male>female) as well as in the lifetime occurrence of depressive disorders (2:1 female>male) (Abel et al, 2010; Parker & Brotchie, 2010). Thus sex and stress interact in the sculpting of potentially vulnerable circuits during adolescence. Our long-term goal is to understand how the neural changes during adolescence can go awry to precipitate psychopathologies in a sexually dimorphic pattern. The central hypothesis of the present proposal is that there are sex differences in the timing of pruning during adolescence that result in differential vulnerabilitiesto stress.

描述（由申请人提供）：青春期是一个独特的过渡时间，长期以来一直在情绪动荡，增加成瘾的脆弱性以及抑郁症和精神分裂症等精神疾病的发作。此时发生的神经重组可能会导致包括压力在内的环境的脆弱性增加。人类的前额叶皮层，尤其是在青春期的大小降低，每种性别的时机和轨迹的不同时间和斜率（Lenroot等，2007）。这意味着男性和女性的大小降低的细胞基础也必须有所不同。神经元，树突，突触和受体的修剪发生在人类和其他物种的青春期前额叶皮质中（Huttenlocher，1979; Lewis，1997; Andersen等，2000; Markham等，2007; Markham等，2007），并且在稀有的Intercance中存在性别差异。修剪的时间将在AIM 1中进行研究，在AIM 2中，性别差异的含义将在AIM 2中测试。在人类青春期期间的压力是心理病理学的已知倾向，可以促进症状（Grant等，2004; Arnsten，2011），表明正常修长的破坏。青少年对压力的行为反应存在性别差异（Romeo; 2010; Wilkin等，2012）。这可能导致青少年发作期间精神分裂症的发病率和严重程度（1.4：1雄性>女）以及抑郁症的终生发生（2：1雌性>雄性）（Abel等，2010; Parker＆Brotchie，2010年）。因此，性别和压力在青春期潜在脆弱的电路的雕刻中相互作用。我们的长期目标是了解青少年期间的神经变化如何出现在性二态模式下促进心理病理学。本提议的中心假设是，青春期修剪的时机存在性别差异，从而导致弱点差异。