Neuroendocrine Mechanisms Regulating Adolescent Social Development

调节青少年社会发展的神经内分泌机制

• 批准号: 1754878
• 负责人: Matthew Paul
• 金额: $ 67万
• 依托单位: SUNY at Buffalo
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-06-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1754878&HistoricalAwards=false
• 关键词: Neuroendocrine; Mechanisms; Regulating; Adolescent; Social

Adolescence is a time of remarkable development in social, emotional, and cognitive abilities. However, it is also a time of increased vulnerability to mental health disorders and increased sensation seeking thought to underlie an elevated incidence of deaths and injuries from accidents. These behavioral changes are accompanied by complex interactions between hormones and the brain, and a major challenge is to parse out which neural and hormonal factors are responsible for adolescent behavioral changes and which merely coincide with them. Activation of pubertal hormones in adolescence is the primary candidate. In this research project, a new model is introduced that makes use of a seasonally-breeding hamster species, for which the timing of puberty can be controlled simply by manipulating day length -- hamsters born and raised in long, summer-like day lengths undergo puberty early, whereas those born in short, winter-like day lengths delay puberty by several months in order to prevent breeding during the harsh winter months. The proposed experiments use this model to test the role of pubertal hormones in adolescent social behavioral and neural development. This research will advance understanding of the neural and hormonal factors that both drive adolescent social development and underlie the increased vulnerability of this life stage. An additional part of this project is the principal investigator's oversight of a student-run outreach program with the Buffalo Zoo to create zoo camps designed to spark children's interest in the sciences. The inclusion of University student participation promotes and provides training in science outreach and early childhood science education. This project tests the role of pubertal hormones in adolescent behavioral and neural development, focusing on play behavior, the predominant social behavior in adolescent animals, and the 'social' vasopressin (VP) pathway, a pathway recently implicated in adolescent social development. The goal of Aim 1 is to determine the role of pubertal hormones in the development of the 'social' VP pathway. Its neuroanatomical development in the hamster model is being uncovered using immunohistochemistry and in situ hybridization. Aim 2 serves to determine the projections through which the 'social' VP pathway regulates play. The role of four key projection areas is being tested with site-specific infusions of a VP agonist and antagonist to determine how this pathway regulates social development. Aim 3 involves an initial test of the role of estradiol in early adolescent behavior. Estradiol levels are measured using enzyme immunoassay in the hamster model to determine whether day length impacts circulating estradiol levels in juvenile hamsters. This research program will begin to map puberty-dependent and puberty-independent neural circuits and specify how they interact to regulate adolescent social development.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

青春期是社会、情感和认知能力显著发展的时期。然而，这也是一个更容易受到精神健康障碍和寻求刺激的时期，这被认为是事故伤亡发生率上升的基础。这些行为变化伴随着激素和大脑之间复杂的相互作用，一个主要的挑战是解析出哪些神经和激素因素对青少年的行为变化负责，哪些只是与它们相吻合。青春期青春期激素的激活是主要的候选因素。在这个研究项目中，引入了一个新的模型，利用季节性繁殖的仓鼠物种，青春期的时间可以简单地通过操纵白天的长度来控制——在长而像夏天一样的白天出生和长大的仓鼠会提前进入青春期，而那些在短而像冬天一样的白天出生的仓鼠会将青春期推迟几个月，以防止在严酷的冬季繁殖。本实验采用该模型来检验青春期激素在青少年社会行为和神经发育中的作用。这项研究将促进对神经和激素因素的理解，这些因素既推动了青少年的社会发展，又使这一生命阶段的脆弱性增加。这个项目的另一个部分是首席研究员监督学生与布法罗动物园的外展计划，该计划旨在创建动物园营地，以激发孩子们对科学的兴趣。大学学生的参与促进并提供了科学推广和幼儿科学教育方面的培训。该项目测试了青春期激素在青少年行为和神经发育中的作用，重点关注玩耍行为，青少年动物的主要社会行为，以及“社会性”抗利尿激素（VP）途径，这一途径最近与青少年社会发展有关。目的1是确定青春期激素在“社会”VP通路发展中的作用。利用免疫组织化学和原位杂交技术揭示了其在仓鼠模型中的神经解剖学发育。目标2旨在确定“社交”VP通路调节游戏的投射。四个关键投射区域的作用正在通过特定部位的静脉注射VP激动剂和拮抗剂进行测试，以确定这一途径如何调节社会发展。目的3涉及雌二醇在早期青少年行为中的作用的初步测试。在仓鼠模型中使用酶免疫分析法测量雌二醇水平，以确定日长是否影响幼年仓鼠循环雌二醇水平。这个研究项目将开始绘制青春期依赖和青春期独立的神经回路，并明确它们如何相互作用来调节青少年的社会发展。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Prepubertal ovarian inhibition of Light/Dark Box exploration and novel object investigation in juvenile Siberian hamsters

青春期前卵巢对幼年西伯利亚仓鼠明/暗盒探索和新物体研究的抑制

• DOI: 10.1016/j.yhbeh.2019.07.007
• 发表时间: 2019
• 期刊: Hormones and Behavior
• 影响因子: 3.5
• 作者: Kyne, R.F.;Barrett, A.R.;Brown, L.M.;Paul, M.J.
• 通讯作者: Paul, M.J.

Mutation in the vasopressin gene eliminates the sex difference in social reinforcement in adolescent rats

加压素基因突变消除了青春期大鼠社会强化的性别差异

• DOI: 10.1016/j.physbeh.2019.04.004
• 发表时间: 2019
• 期刊: Physiology & Behavior
• 影响因子: 2.9
• 作者: Schatz, K.C.;Martin, C.D.;Ishiwari, K.;George, A.M.;Richards, J.B.;Paul, M.J.
• 通讯作者: Paul, M.J.

The role of glucagon-like peptide-1 (GLP-1) in fluid and food intakes in vasopressin-deficient Brattleboro rats

• DOI: 10.1016/j.physbeh.2023.114093
• 发表时间: 2023-01-28
• 期刊: PHYSIOLOGY & BEHAVIOR
• 影响因子: 2.9
• 作者: Brakey，Destiny J.;Schatz，Kelcie C.;Daniels，Derek
• 通讯作者: Daniels，Derek

Sex differences in auditory brainstem response audiograms from vasopressin-deficient Brattleboro and wild-type Long-Evans rats

• DOI: 10.1371/journal.pone.0222096
• 发表时间: 2019-08-30
• 期刊: PLOS ONE
• 影响因子: 3.7
• 作者: Charlton, Payton E.;Schatz, Kelcie C.;Dent, Micheal L.
• 通讯作者: Dent, Micheal L.

Viral rescue of magnocellular vasopressin cells in adolescent Brattleboro rats ameliorates diabetes insipidus, but not the hypoaroused phenotype

• DOI: 10.1038/s41598-019-44776-1
• 发表时间: 2019-06-03
• 期刊: SCIENTIFIC REPORTS
• 影响因子: 4.6
• 作者: Schatz, K. C.;Brown, L. M.;Paul, M. J.
• 通讯作者: Paul, M. J.