Adolescent environmental enrichment induces social resilience and alters neural gene expression in a selectively bred rodent model with anxious phenotype

IF 4.3 2区 医学 Q1 NEUROSCIENCES
Angela May O'Connor , Megan Hastings Hagenauer, Liam Cannon Thew Forrester, Pamela M. Maras, Keiko Arakawa, Elaine K. Hebda-Bauer, Huzefa Khalil, Evelyn R. Richardson, Farizah I. Rob, Yusra Sannah, Stanley J. Watson Jr., Huda Akil
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引用次数: 0

Abstract

Stress is a major influence on mental health status; the ways that individuals respond to or copes with stressors determine whether they are negatively affected in the future. Stress responses are established by an interplay between genetics, environment, and life experiences. Psychosocial stress is particularly impactful during adolescence, a critical period for the development of mood disorders. In this study we compared two established, selectively-bred Sprague Dawley rat lines, the “internalizing” bred Low Responder (bLR) line versus the “externalizing” bred High Responder (bHR) line, to investigate how genetic temperament and adolescent environment impact future responses to social interactions and psychosocial stress, and how these determinants of stress response interact. Male bLR and bHR rats were exposed to social and environmental enrichment in adolescence prior to experiencing social defeat and were then assessed for social interaction and anxiety-like behavior. Adolescent enrichment caused rats to display more social interaction, as well as nominally less social avoidance, less submission during defeat, and resilience to the effects of social stress on corticosterone, in a manner that seemed more notable in bLRs. For bHRs, enrichment also caused greater aggression during a neutral social encounter and nominally during defeat, and decreased anxiety-like behavior. To explore the neurobiology underlying the development of social resilience in the anxious phenotype bLRs, RNA-seq was conducted on the hippocampus and nucleus accumbens, two brain regions that mediate stress regulation and social behavior. Gene sets previously associated with stress, social behavior, aggression and exploratory activity were enriched with differential expression in both regions, with a particularly large effect on gene sets that regulate social behaviors. Our findings provide further evidence that adolescent enrichment can serve as an inoculating experience against future stressors. The ability to induce social resilience in a usually anxious line of animals by manipulating their environment has translational implications, as it underscores the feasibility of intervention strategies targeted at genetically vulnerable adolescent populations.

青少年环境强化可诱导社会适应能力,并改变选择性培育的焦虑表型啮齿动物模型的神经基因表达
压力是影响心理健康状况的一个重要因素;个人应对或处理压力的方式决定了他们未来是否会受到负面影响。压力反应是由遗传、环境和生活经历相互作用而形成的。社会心理压力在青春期的影响尤为明显,而青春期正是情绪障碍发展的关键时期。在这项研究中,我们比较了两种成熟的、经过选择性繁殖的 Sprague Dawley 大鼠品系,即 "内化型 "低反应品系(bLR)和 "外化型 "高反应品系(bHR),以研究遗传气质和青春期环境如何影响未来对社会交往和社会心理压力的反应,以及这些压力反应的决定因素如何相互作用。雄性 bLR 和 bHR 大鼠在经历社交失败之前的青春期暴露于社交和环境强化中,然后对其社交互动和焦虑样行为进行评估。青春期的丰富环境使大鼠表现出更多的社会交往,以及名义上较少的社会回避、失败时较少的屈服和对社会压力对皮质酮影响的恢复力,这种方式似乎在 bLRs 中更为明显。对 bHRs 而言,富集也会导致它们在中性社交中和名义上在失败时表现出更强的攻击性,并减少焦虑样行为。为了探索焦虑表型 bLRs 发展社会适应能力的神经生物学基础,研究人员对海马和脑核这两个介导压力调节和社会行为的脑区进行了 RNA-seq。以前与压力、社会行为、攻击性和探索活动相关的基因组在这两个区域都有差异表达,尤其是对调节社会行为的基因组影响更大。我们的研究结果进一步证明,青春期强化训练可以作为一种预防性经历,抵御未来的压力。通过操纵环境来诱导通常焦虑的动物系的社会适应能力具有转化意义,因为它强调了针对基因脆弱的青少年群体采取干预策略的可行性。
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来源期刊
Neurobiology of Stress
Neurobiology of Stress Biochemistry, Genetics and Molecular Biology-Biochemistry
CiteScore
9.40
自引率
4.00%
发文量
74
审稿时长
48 days
期刊介绍: Neurobiology of Stress is a multidisciplinary journal for the publication of original research and review articles on basic, translational and clinical research into stress and related disorders. It will focus on the impact of stress on the brain from cellular to behavioral functions and stress-related neuropsychiatric disorders (such as depression, trauma and anxiety). The translation of basic research findings into real-world applications will be a key aim of the journal. Basic, translational and clinical research on the following topics as they relate to stress will be covered: Molecular substrates and cell signaling, Genetics and epigenetics, Stress circuitry, Structural and physiological plasticity, Developmental Aspects, Laboratory models of stress, Neuroinflammation and pathology, Memory and Cognition, Motivational Processes, Fear and Anxiety, Stress-related neuropsychiatric disorders (including depression, PTSD, substance abuse), Neuropsychopharmacology.
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