Social regulation of oxidative stress in the brain
大脑氧化应激的社会调节
基本信息
- 批准号:10730899
- 负责人:
- 金额:$ 44.33万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-09-01 至 2026-08-31
- 项目状态:未结题
- 来源:
- 关键词:AddressAffectAggressive behaviorAndrogen ReceptorAndrogensAnimal BehaviorAnimalsAntioxidantsAutomobile DrivingBiological ModelsBrainBrain DiseasesBrain regionCell physiologyChronicChronic stressCichlidsCompetitive BehaviorComplexConflict (Psychology)DataDevelopmentDiseaseEquilibriumFemaleFishesFunctional disorderGoalsGonadal structureHealthHomeHomeostasisIndividualInterventionLaboratoriesLifeLinkMammalsMental DepressionMental HealthMental disordersModelingMolecularNeuroanatomyNeurodegenerative DisordersNeurosecretory SystemsOutcomeOxidation-ReductionOxidative RegulationOxidative StressOxidative Stress InductionPartner in relationshipPatternPhenotypePsychopathologyPublic HealthReactive Oxygen SpeciesReceptor SignalingRegulationResearchRiskRodentRoleSocial DominanceSocial EnvironmentSocial statusSourceStressSyntenySystemTerritorialityTestingTestisTestosteroneTranscriptional RegulationWorkage relatedbrain healthexperiencehypothalamic pituitary gonadal axisimprovedinnovationinsightmalenervous system disorderneurogenomicsnoveloxidative damagepharmacologicpsychological stressorreproductivesocialsocial competitionsocial defeatsocial relationshipssocial stresssocial stressorstress managementtherapeutic targettranscriptometranscriptome sequencingundergraduate student
项目摘要
PROJECT SUMMARY
The social environment can have both positive and negative impacts on health. In many social animals,
individuals are competing for high social status, which can result in distinct social stressors for individuals with
both high and low social status. Social stress can cause oxidative stress in the brain, which is a key mechanism
driving a variety of mental health and neurodegenerative diseases. The overall objective of this proposal is to
characterize the impact of social status on oxidative stress and its regulation across the brain. While low social
status can be a source of chronic stress, high social status is also stressful - especially in natural conditions
where defending social dominance is challenging. We hypothesize that the impact of social status on brain
oxidative stress arises from a dynamic interplay between social stress and the hypothalamic-pituitary-gonadal
(HPG) axis. Activation of this neuroendocrine center leads to the release of androgens, which facilitates
competitive behavior, but is also known to modulate oxidative stress. We will test our hypothesis using the highly
social cichlid fish Astatotilapia burtoni, a well-established model system for neurogenomics and integrated animal
behavior, due in part to the large synteny and shared homologies of the neuroendocrine system relative to
mammals. Male A. burtoni exist as two reversible phenotypes: dominant and subordinate. Dominant males
aggressively defend a territory, have large gonads due to an upregulated HPG axis, and mate with females,
while subordinate males are nonterritorial and reproductively suppressed. Social status can be readily
manipulated and tracked in replicate groups. The proposal has the following specific aims: (1) Test how social
status and HPG axis activity impact oxidative stress patterns across the brain using various markers of oxidative
damage and antioxidant defense. (2) Determine the molecular mechanisms by which social status and HPG axis
activity influence brain oxidative stress. At the completion of these aims, we will provide insights into how social
status and HPG axis activity impact brain health and oxidative balance at the organismal level. The proposal is
innovative because it investigates the regulation of oxidative balance in the brain in both dominant and
subordinate individuals in a novel model system with a distinctly stratified dominance hierarchy. The proposed
work is significant because oxidative stress in the brain has been causally linked to a range of psychopathologies,
including depression and age-related brain disease. Our results will provide useful information that will ultimately
be important for improving public health. The proposed research will expose undergraduate students to
hypothesis-driven research addressing biomedically relevant questions.
项目总结
项目成果
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Peter Dijkstra其他文献
Peter Dijkstra的其他文献
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