Depression-like behavior is associated with deficits in cognition and hippocampal neurogenesis in a subset of spinally contused male, but not female, rats

IF 8.8 2区 医学 Q1 IMMUNOLOGY
Alex Stefanov , Kiralyn Brakel , Josephina Rau , Rose M. Joseph , Corey Guice , Kendall Araguz , Annebel Hemphill , Jessica Madry , Andrew Irion , Swapnil Dash , Karienn A. Souza , Michelle A. Hook
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Abstract

Depression and cognitive deficits present at higher rates among people with spinal cord injury (SCI) compared to the general population, yet these SCI comorbidities are poorly addressed. Sex and age appear to play roles in depression incidence, but consensus on the direction of their effects is limited. Systemic and cortical inflammation and disruptions in hippocampal neurogenesis have been identified as potential treatment targets, but a comprehensive understanding of these mechanisms remains elusive.
We used a rodent SCI model to interrogate these gaps in knowledge. We examined post-injury depression-like behavior and cognitive deficits, as well as the association between affect, cognition, chronic hippocampal inflammation and hippocampal neurogenesis, in young and middle-aged male and female Sprague-Dawley rats. Depression-like behavior manifested in male and female subsets of SCI rats irrespective of age, at rates commensurate with the incidence of clinical depression. Changes in components of behavior were driven by sex and age, and affective outcomes were independent of common post-injury pathophysiological outcomes including locomotor functional deficits and spinal lesion severity. Interestingly, however, only male depression-like SCI rats exhibited deficits in hippocampal-associated spatial cognition. Neurogenesis was also disrupted in only SCI males in regions of the hippocampus responsible for affective outcomes. Decreased neurogenesis among middle-aged male subjects coincided with increases in numbers of the pro-inflammatory markers CD86 and iNOS, while middle-aged females had increased numbers of cells expressing Iba-1 and anti-inflammatory marker CD206.
Overall, the present data suggest that post-SCI depression and cognition may be affected, in part, by sex- and age-dependent changes in hippocampal neurogenesis and inflammation. Hippocampal neurogenesis is a potential target to address psychological wellbeing after SCI, but therapeutic strategies must carefully consider sex and age as biological variables.
在一部分脊髓挫伤的雄性大鼠(而非雌性大鼠)中,抑郁样行为与认知缺陷和海马神经发生有关。
与普通人群相比,脊髓损伤(SCI)患者出现抑郁和认知障碍的比例更高,但这些 SCI 并发症却很少得到关注。性别和年龄似乎对抑郁症的发病率有影响,但对其影响方向的共识却很有限。系统性和皮层炎症以及海马神经发生的破坏已被确定为潜在的治疗目标,但对这些机制的全面了解仍然遥遥无期。我们利用啮齿动物 SCI 模型来探究这些知识空白。我们研究了中青年雄性和雌性 Sprague-Dawley 大鼠受伤后的抑郁样行为和认知障碍,以及情感、认知、慢性海马炎症和海马神经发生之间的关联。在雌雄SCI大鼠亚群中,抑郁样行为的表现与年龄无关,其发生率与临床抑郁症的发生率相当。行为成分的变化受性别和年龄的影响,情感结果与常见的损伤后病理生理结果(包括运动功能障碍和脊柱损伤严重程度)无关。但有趣的是,只有雄性抑郁样损伤大鼠表现出与海马相关的空间认知障碍。只有雄性 SCI 大鼠负责情感结果的海马区域的神经发生也受到破坏。中年男性受试者神经发生减少的同时,促炎症标记物 CD86 和 iNOS 的数量增加,而中年女性受试者表达 Iba-1 和抗炎症标记物 CD206 的细胞数量增加。总之,本研究数据表明,SCI 后抑郁症和认知能力可能部分受到海马神经发生和炎症的性别和年龄变化的影响。海马神经发生是解决损伤后心理健康问题的潜在目标,但治疗策略必须仔细考虑性别和年龄这些生物变量。
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来源期刊
CiteScore
29.60
自引率
2.00%
发文量
290
审稿时长
28 days
期刊介绍: Established in 1987, Brain, Behavior, and Immunity proudly serves as the official journal of the Psychoneuroimmunology Research Society (PNIRS). This pioneering journal is dedicated to publishing peer-reviewed basic, experimental, and clinical studies that explore the intricate interactions among behavioral, neural, endocrine, and immune systems in both humans and animals. As an international and interdisciplinary platform, Brain, Behavior, and Immunity focuses on original research spanning neuroscience, immunology, integrative physiology, behavioral biology, psychiatry, psychology, and clinical medicine. The journal is inclusive of research conducted at various levels, including molecular, cellular, social, and whole organism perspectives. With a commitment to efficiency, the journal facilitates online submission and review, ensuring timely publication of experimental results. Manuscripts typically undergo peer review and are returned to authors within 30 days of submission. It's worth noting that Brain, Behavior, and Immunity, published eight times a year, does not impose submission fees or page charges, fostering an open and accessible platform for scientific discourse.
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