Psychosocial stress, cardio-respiratory fitness, and the medial temporal hippocampal system in Black emerging adults

总结/摘要 本研究的目的是探讨心肺适能（CRF）和慢性心理社会 应激对18 ~ 25岁成年黑人内侧颞海马（MTH）系统的调节作用 他们每天都暴露在社会心理压力下，通过种族主义评级的慢性压力的透镜进行检查。 成人初显期是大多数成人初显期所经历的一个身份探索的生命阶段 压力很大黑人新兴的成年人有种族主义相关的慢性压力的额外负担。慢性压力和 CRF是众所周知的MTH系统的相反调节剂，但这种调节的神经生物学基础 人类是未知的。理论和动物模型都指出了运动的共同神经生物学基础- 和应力诱导的调制MTH系统：上调与下调，分别为可塑性机制， 海马体中的寄生虫这些模型突出了脑源性神经营养因子（BDNF）的表达， 成年出生的，未成熟的神经元在海马齿状回（DG）子区的重要作用， 这种计算过程称为模式分离（PS）。PS对于记忆的形成至关重要， 焦虑和抑郁。无论是非稳态负荷，生理'磨损'的反应，慢性压力 跨多个生物系统与MTH系统功能相关尚不清楚，但对 站在MTH系统在精神和大脑健康的作用。相反，CRF越大， 更好的心理健康和MTH系统的功能和结构的年轻人。尽管有这样的知识，它是不- 已知MTH可塑性的推定标志物（例如，血清BDNF，CRF）和非稳态负荷相互作用， 在新生儿中的MTH系统。在这里，我们建议检查MTH系统可塑性结合 CRF和血清BDNF测量与种族负担的措施和DG-CA 3电路评估 使用高分辨率的功能和结构MRI，以及记忆辨别任务的表现， 税PS。我们的中心假设是，种族主义负担将与MTH系统功能呈负相关， CRF与非稳态负荷呈正相关，与MTH系统功能和选择性呈正相关。 朗姆酒BDNF和负与非稳态负荷的黑人新兴的成年人。我们将检验这一假设， 三个具体目标。目的1研究CRF对MTH系统、血清BDNF和非稳态负荷的影响， 和目标2将审查种族主义负担的影响，评估使用的措施， 歧视的文化和结构性种族主义，对MTH系统和allostatic负荷。目标3是探索性的， 将研究累积的种族主义负担和CRF对MTH系统的影响，通过allo- 静态负荷，血清BDNF和心理健康使用结构方程建模方法。一个积极的结果 这项研究的结果将为非稳态负荷和神经可塑性机制之间的相互作用提供证据 作为影响MTH系统的对立机制，并将填补关于种族主义的重要知识空白， den作为一个负调制器的大脑健康和MTH可塑性在黑人新兴的成年人。

SUMMARY/ABSTRACT The goal of this proposed research is to examine how cardiorespiratory fitness (CRF) and chronic psychosocial stress modulate the medial temporal hippocampal (MTH) system in Black emerging adults aged 18 to 25 years who are exposed to daily psychosocial stress, examined through the lens of racism-rated chronic stress. Emerging adulthood is a life period of identity exploration that is experienced by the majority of emerging adults as stressful. Black emerging adults have the added burden of racism-related chronic stress. Chronic stress and CRF are well-known, opposite modulators of the MTH system, but the neurobiological basis of this modulation in humans is unknown. Theoretical and animal models point to a shared neurobiological basis for exercise- and stress-induced modulation of the MTH system: up- vs. downregulation, respectively, of plasticity mecha- nisms in the hippocampus. These models highlight expression of brain derived neurotrophic factor (BDNF) and an important role for adult-born, immature neurons in the dentate gyrus (DG) subfield of the hippocampus in a computational process known as pattern separation (PS). PS is critical for memory formation and implicated in anxiety and depression. Whether allostatic load, the physiological ‘wear and tear’ response to chronic stress across multiple biological systems is associated with MTH system function is unclear, but critical to under- standing the role of the MTH system in mental and brain health. In contrast, greater CRF is associated with better mental health and MTH system function and structure in young adults. Despite this knowledge it is un- known how putative markers of MTH plasticity (e.g., serum BDNF, CRF) and allostatic load interact to modu- late the MTH system in emerging adults. Here, we propose to examine MTH system plasticity by combining CRF and serum BDNF measurement with measures of racism burden and with DG-CA3 circuit assessments using high-resolution functional and structural MRI, and performance on mnemonic discrimination tasks de- signed to tax PS. Our central hypothesis is that racism burden will negatively correlate with MTH system func- tion and positively with allostatic load, whereas CRF will positively correlate with MTH system function and se- rum BDNF and negatively with allostatic load in Black emerging adults. We will examine this hypothesis with three Specific Aims. Aim 1 will examine impact of CRF on the MTH system, serum BDNF, and allostatic load, and Aim 2 will examine the impact of racism burden, assessed using measures ranging from perceived racial discrimination to cultural and structural racism, on the MTH system and allostatic load. Aim 3 is exploratory and will examine the impact of cumulative racism burden and CRF on the MTH system mechanistically via allo- static load, serum BDNF and mental health using a structural equation modeling approach. A positive outcome of this research will provide evidence for an interplay between allostatic load and neuroplasticity mechanisms as opposing mechanisms affecting the MTH system and will fill an important knowledge gap about racism bur- den as a negative modulator of brain health and MTH plasticity in Black emerging adults.