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

摘要/摘要 这项拟议的研究的目标是检查心肺健康(CRF)和慢性心理社会 应激对18-25岁黑人新秀的内侧颞叶海马区系统的调节作用 他们暴露在日常的心理社会压力下，通过种族主义评级的慢性压力的镜头进行检查。 成年初期是大多数成年初期经历的身份探索的人生阶段。 压力一样大。黑人初出茅庐的成年人承受着与种族主义相关的长期压力。慢性应激和 CRF是众所周知的MTH系统的相反调节器，但这种调节的神经生物学基础 在人类中的作用是未知的。理论和动物模型表明，锻炼有共同的神经生物学基础-- 和应力诱导的MTH系统的调制：分别上调和下调塑性机制- 海马体中的神经症。这些模型强调脑源性神经营养因子(BDNF)和 成年出生的未成熟神经元在海马齿状回(DG)亚区的重要作用 称为模式分离(PS)的计算过程。PS对记忆的形成至关重要，并与 焦虑和抑郁。无论是恒定负荷，生理‘磨损’对慢性应激的反应 跨多个生物系统与MTH系统功能相关尚不清楚，但对下- 站在MTH系统在精神和大脑健康方面的作用。相比之下，更大的CRF与 年轻人的心理健康和MTH系统的功能和结构更好。尽管知道了这一点，但它是不- 已知MTH可塑性的推定标记物(如血清BDNF、CRF)和不平衡负荷如何相互作用来调节 新生成人的MTH系统较晚。在这里，我们建议通过组合来检验MTH系统的可塑性 用种族主义负荷测量和DG-CA3巡回评估测量CRF和血清BDNF 使用高分辨率的功能和结构磁共振成像，并在记忆辨别任务中的性能去 签约缴税PS。我们的中心假设是种族主义负担将与MTH系统功能负相关。 CRF与MTH系统功能、Se呈正相关。 朗姆酒BDNF，与黑人初露头角的成人的平衡负荷呈负相关。我们将用以下方法检验这一假设 三个具体目标。目的1研究CRF对MTH系统、血清BDNF和稳态负荷的影响。 目标2将检查种族主义负担的影响，使用从感知到的种族 对文化和结构性种族主义的歧视、对MTH系统和非平衡负荷的歧视。目标3是探索性的， 将审查累积种族主义负担和CRF对MTH系统的影响 静态负荷、血清脑源性神经营养因子和心理健康的结构方程建模方法。积极的结果 这项研究的结果将为平衡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认识空白，但-- DEN是黑人初露头角的成年人大脑健康和MTH可塑性的负面调节因子。

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.