Mechanisms for Environmental and Genetic Reversal of Gender Biased Behavior

性别偏见行为的环境和遗传逆转机制

• 批准号: 7458065
• 负责人: SUSAN C.P. RENN
• 金额: $ 22.94万
• 依托单位: REED COLLEGE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-06-01 至 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7458065
• 关键词: Address; African; Aggressive behavior; Animal Model; Animals; Area; Behavior; Behavioral; Bioinformatics; Biological Models; Biological Neural Networks; Brain; Brain region; Candidate Disease Gene; Caring; Cichlids; Communities; Complex; Condition; Coupling; Data; Environment; Estradiol; Exhibits; Female; Foundations; Gender Role; Gene Expression; Genes; Genetic; Hormonal; Hormones; Human; In Situ Hybridization; Individual; Localized; Maintenance; Measures; Medical Research; Modeling; Molecular; Molecular Profiling; Neuroanatomy; Neurons; Neurosciences Research; Normal Range; Pair Bond; Phenotype; Physiological; Physiology; Plastics; Process; Public Health; Range; Recruitment Activity; Regulation; Reproduction; Research; Sex Behavior; Sex Bias; Sex Characteristics; Site; Social Behavior; Social Environment; Societies; System; Systems Biology; Testing; Testosterone; Variant; Work; base; behavior observation; egg; genome sequencing; indexing; male; neurochemistry; positional cloning; relating to nervous system; sex; steroid hormone; tool; trait

DESCRIPTION (provided by applicant): The relationship between sex and behavior is a persistent question from society, as well as the medical and the research communities. Neuroscience research has undeniably demonstrated that the genetic sex of an individual has broad ranging effects on both anatomical brain areas and behaviors. However, a parallel line of research has demonstrated the inaccuracy of predicting phenotype based solely on genome sequence, thus implicating environmental influence. I propose to contrast the mechanisms that underlie genetic and environmental influences on gender biased behaviors using a pair-bonded monogamous animal model of parental care, genus Julidochromis, African cichlid fishes. I take a "systems biology" approach that quantitatively integrates phenotype data from multiple levels including neural gene expression, hormone titers, and behavioral observations. The African Cichlid fishes provide a unique opportunity to observe naturalistic behaviors in which gender-biased behaviors can be reversed by either environmental effects or genetic effects. The behavioral phenotypes, hormone levels, and gene expression profiles can therefore be assessed in these three paradigms 1) conventional gender-role 2) environmental reversal 3) genetic reversal. Within the conventional gender-bias paradigm the males are larger, more aggressive and territorial, while the females provide the egg care and nest maintenance. In this same species, altering the social environment, will reverse gender-biased behaviors, while in a closely related species the gender-biased behaviors are reversed by genetic background. Covariance analysis across multiple levels of phenotype will identify molecular modules that correlate with gender biased behaviors independent of sex. Paradigm 1 will be used as baseline from which to measure and contrast the two reversal phenotypes, and the molecular modules that are recruited in paradigms 2 & 3 will be contrasted in order to evaluate the mechanisms that underlie environmental and genetic influence. The localization of gender-biased neuronal gene expression will indicate neuroanatomical sites for regulation of these behaviors and thus lay the foundation for a model system in which to address the relationship of neural and molecular networks that orchestrate plastic and biased gender-role behavior. PUBLIC HEALTH RELEVANCE The great influence of sex on the brain is undeniable at the level of neuroanatomy, neurochemistry, brain function, and even behavior. The proposed systems level research integrates data from behavioral, physiological and molecular level in order to contrast mechanisms by which genes and the environment influence gender-biased behaviors and identify neuroanatomical sites important for the regulation of these behaviors. I use an animal model (cichlid fish) to study complex social behaviors that are directly relevant to the broad range of normal sex-related differences in human social behaviors as well as psychiatric conditions that show both genetic and environmental components.

描述（由申请人提供）：性与行为之间的关系是社会以及医学和研究界的一个持续问题。神经科学研究已经证明，个体的遗传性别对大脑解剖区域和行为都有广泛的影响。然而，一项平行的研究表明，仅根据基因组序列预测表型是不准确的，因此涉及环境影响。我建议对比的机制，基础上的遗传和环境的影响，性别偏见的行为，父母照顾，属Julidochromis，非洲慈鲷鱼一对一夫一妻制的动物模型。我采取了“系统生物学”的方法，定量整合了多个层面的表型数据，包括神经基因表达，激素滴度和行为观察。非洲慈鲷鱼提供了一个独特的机会，观察自然的行为，其中性别偏见的行为可以被逆转的环境影响或遗传效应。行为表型、激素水平和基因表达谱因此可以在这三个范例中进行评估：1）常规性别角色2）环境逆转3）遗传逆转。在传统的性别偏见范式中，男性更大，更具侵略性和领土性，而女性则提供鸡蛋护理和巢穴维护。在同一物种中，改变社会环境会逆转性别偏见行为，而在密切相关的物种中，性别偏见行为会被遗传背景逆转。跨多个表型水平的协方差分析将识别与性别偏见行为相关的分子模块，而与性别无关。范例1将用作基线，从其测量和对比两种逆转表型，并且将对比在范例2和3中招募的分子模块，以评估环境和遗传影响的基础机制。性别偏见的神经元基因表达的本地化将指示这些行为的调节的神经解剖学位点，从而为模型系统奠定基础，在该模型系统中，以解决协调塑性和偏见的性别角色行为的神经和分子网络的关系。在神经解剖学、神经化学、大脑功能甚至行为的层面上，性对大脑的巨大影响是不可否认的。拟议的系统水平的研究整合了来自行为，生理和分子水平的数据，以对比基因和环境影响性别偏见行为的机制，并确定对这些行为的调节重要的神经解剖部位。我使用动物模型（慈鲷鱼）来研究复杂的社会行为，这些行为与人类社会行为中广泛的正常性别相关差异以及显示遗传和环境成分的精神疾病直接相关。