DISSERTATION RESEARCH: Neuroendocrine Mechanisms of Seasonal Aggression in Female Siberian Hamsters (Phodopus sungorus)

论文研究：雌性西伯利亚仓鼠（Phodopus sungorus）季节性攻击的神经内分泌机制

• 批准号: 1406063
• 负责人: Gregory Demas
• 金额: $ 2万
• 依托单位: Indiana University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2016-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1406063&HistoricalAwards=false
• 关键词: DISSERTATION; RESEARCH; Neuroendocrine; Mechanisms; Seasonal

Aggression is a widespread naturally-occurring behavior serving a range of adaptive functions including access to mates and resources. Testosterone produced by the gonads is frequently associated with high levels of aggression. However, in seasonal breeding animals aggression can be both intense and widespread during the non-breeding season when testosterone levels are undetectable. This means that aggression is regulated by more than one mechanism and there is little understanding of how non-breeding aggression is regulated. This research seeks to understand the physiological mechanisms that underlie seasonal variation of aggression using female Siberian hamsters as a model. This work is highly integrative and unlike most other studies that examine single factors it will consider many relevant endocrine parameters and their interactions to understand how the brain and hormones function to control seasonal aggression in females. These studies will provide important insights into the physiological mechanisms mediating aggression, and social behavior more broadly. Additionally, this proposal will allow for the continued mentorship of undergraduates and high school students in research directly related to this work. Communication of these research findings will include public lectures and scientific conferences, and journal articles, as well as specialized regional symposia and organizations focused on the advancement of underrepresented minorities in the sciences.The researchers' data so far show that melatonin, the hormonal signal encoding photoperiod, drives seasonal changes in aggression, and further that adrenal hormones, such as DHEA, rather than gonadal hormones, may indirectly regulate aggression via conversion to active androgens or estrogens during periods when animals are non-reproductive. To examine seasonal switching from a gonadal to adrenal source of hormone, the proposed research tests the hypotheses that DHEA mediates non-breeding season aggression and that melatonin regulates DHEA release and its conversion to active hormones, which can then act on neural receptors. Specific Aim 1 will link seasonal changes in aggression and seasonal melatonin cues to neural receptor profiles (androgen and estrogen receptors) as well as a converting enzyme (aromatase, the enzyme that converts T to estradiol), via immunocytochemistry. Specific Aim 2 will determine whether changes in DHEA levels predict aggression among individuals across seasons by challenging animals in different photoperiods with ACTH, and assessing DHEA release. Lastly, Specific Aim 3 will test the hypothesis that short-day increases in melatonin mediate seasonal changes in DHEA by isolating the adrenal gland from other organs responsible for DHEA release and by using an in vitro bioassay to address localized action of melatonin on this organ and its subsequent production of DHEA. Collectively, the proposed work takes a whole organism approach and examines direct hormonal action on multiple tissues to determine the mechanisms underlying seasonal aggression in female hamsters using multiple levels of analysis. To facilitate proper storage and access of data, manuscripts will be published in open-access format, when possible, and on the lab website. Presentations will be made at international and national conferences, as well as in local venues to lay audiences, including high schools. Following processing of samples for the primary project, samples will be archived, and made accessible for collaborations from interested parties. Lastly, the PI will work with Indiana University Information Technology Services to archive data on the Research Data Complex (RDC), a dedicated server for hosting databases.

攻击性是一种广泛存在的自然行为，具有一系列适应性功能，包括获取配偶和资源。性腺产生的睾酮通常与高水平的攻击性有关。然而，在季节性繁殖的动物中，在非繁殖季节，当睾酮水平检测不到时，攻击性可能会非常强烈和普遍。 这意味着攻击行为受到不止一种机制的调节，并且人们对如何调节非繁殖攻击行为知之甚少。这项研究旨在以雌性西伯利亚仓鼠为模型，了解攻击性季节性变化的生理机制。这项工作是高度综合性的，与大多数其他检查单一因素的研究不同，它将考虑许多相关的内分泌参数及其相互作用，以了解大脑和激素如何发挥作用来控制女性的季节性攻击行为。这些研究将为介导攻击行为和更广泛的社会行为的生理机制提供重要的见解。此外，该提案将允许继续指导本科生和高中生进行与这项工作直接相关的研究。这些研究成果的交流将包括公开讲座和科学会议、期刊文章以及专门的区域研讨会和组织，重点关注科学领域代表性不足的少数群体的进步。迄今为止，研究人员的数据表明，褪黑激素（荷尔蒙信号编码）光周期驱动攻击性的季节性变化，此外，肾上腺激素（例如 DHEA）而不是性腺激素，可以通过转化为活性雄激素或激素来间接调节攻击性。动物非繁殖期的雌激素。为了研究从性腺激素来源到肾上腺激素来源的季节性转换，拟议的研究测试了以下假设：DHEA 介导非繁殖季节的攻击行为，以及褪黑激素调节 DHEA 的释放及其转化为活性激素，然后作用于神经受体。具体目标 1 将通过免疫细胞化学将攻击性的季节性变化和季节性褪黑激素线索与神经受体谱（雄激素和雌激素受体）以及转化酶（芳香酶，将 T 转化为雌二醇的酶）联系起来。具体目标 2 将通过在不同光周期用 ACTH 挑战动物并评估 DHEA 释放来确定 DHEA 水平的变化是否可以预测个体之间的攻击行为。最后，具体目标 3 将通过将肾上腺与负责 DHEA 释放的其他器官隔离，并使用体外生物测定来解决褪黑激素对该器官的局部作用，来检验褪黑激素的短日增加介导 DHEA 季节性变化的假设。随后生产 DHEA。总的来说，拟议的工作采用了整个有机体的方法，并检查了多个组织上的直接激素作用，以确定雌性仓鼠季节性攻击的潜在机制。为了促进数据的正确存储和访问，手稿将在可能的情况下以开放获取格式发布并在实验室网站上发布。演讲将在国际和国家会议上以及在当地场所向非专业观众（包括高中）进行。 在处理主要项目的样本后，样本将被存档，并可供感兴趣的各方合作使用。最后，PI 将与印第安纳大学信息技术服务部合作，将数据存档在研究数据综合体 (RDC) 上，这是一个用于托管数据库的专用服务器。

项目成果

The agonistic adrenal: melatonin elicits female aggression via regulation of adrenal androgens

• DOI: 10.1098/rspb.2015.2080
• 发表时间: 2015-11-22
• 期刊: PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
• 影响因子: 4.7
• 作者: Rendon, Nikki M.;Rudolph, Lauren M.;Demas, Gregory E.
• 通讯作者: Demas, Gregory E.

Bi-directional actions of dehydroepiandrosterone and aggression in female Siberian hamsters: DHEA AND FEMALE AGGRESSION

雌性西伯利亚仓鼠脱氢表雄酮和攻击行为的双向作用：DHEA 和女性攻击行为

• DOI: 10.1002/jez.2001
• 发表时间: 2016
• 期刊: Journal of Experimental Zoology Part A: Ecological Genetics and Physiology
• 作者: Rendon, Nikki M.;Demas, Gregory E.
• 通讯作者: Demas, Gregory E.

DHEA effects on brain and behavior: Insights from comparative studies of aggression

DHEA 对大脑和行为的影响：攻击性比较研究的见解

• DOI: 10.1016/j.jsbmb.2014.05.011
• 发表时间: 2015
• 期刊: The Journal of Steroid Biochemistry and Molecular Biology
• 作者: Soma, Kiran K.;Rendon, Nikki M.;Boonstra, Rudy;Albers, H. Elliott;Demas, Gregory E.
• 通讯作者: Demas, Gregory E.