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A history of juvenile mild malaria exacerbates chronic stress-evoked anxiety-like behavior, neuroinflammation, and decline of adult hippocampal neurogenesis in mice
Journal of Neuroimmunology ( IF 2.9 ) Pub Date : 2020-11-01 , DOI: 10.1016/j.jneuroim.2020.577363 Suman K Guha 1 , Ishita Sarkar 1 , Mandar Patgaonkar 1 , Souvik Banerjee 2 , Siuli Mukhopadhyay 2 , Shobhona Sharma 1 , Sulabha Pathak 1 , Vidita A Vaidya 1
Journal of Neuroimmunology ( IF 2.9 ) Pub Date : 2020-11-01 , DOI: 10.1016/j.jneuroim.2020.577363 Suman K Guha 1 , Ishita Sarkar 1 , Mandar Patgaonkar 1 , Souvik Banerjee 2 , Siuli Mukhopadhyay 2 , Shobhona Sharma 1 , Sulabha Pathak 1 , Vidita A Vaidya 1
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Children residing in high malaria transmission regions are particularly susceptible to malaria. This early-life window is also a critical period for development and maturation of the nervous system, and inflammatory insults during this period may evoke a persistent increase in vulnerability for psychopathology. We employed a two-hit model of juvenile mild malaria and a two-week chronic unpredictable mild stress (CUMS) regime, commencing 60 days post-parasite clearance, to assess whether a history of juvenile infection predisposed the mice towards mood-related behavioral alterations and neurocognitive deficits. We showed that adult mice with a history of juvenile malaria (A-H/JMAL) exhibited heightened CUMS-associated anxiety-like behavior, with no observable change in cognitive behavior. In contrast, mice with a history of adult malaria did not exhibit such enhanced stress vulnerability. At baseline, A-H/JMAL mice showed increased activated microglia within the hippocampal dentate gyrus subfield. This was accompanied by a decrease in proliferating neuronal progenitors, with total number of immature hippocampal neurons unaltered. This neuroinflammatory and neurogenic decline was further exacerbated by CUMS. At day-14 post-CUMS, hippocampi of A-H/JMAL mice showed significantly higher microglial activation, and a concomitant decrease in progenitor proliferation and number of immature neurons. Taken together, these results suggest that a history of juvenile mild malaria leaves a neuroinflammatory mark within the hippocampal niche, and this may contribute to a heightened stress response in adulthood. Our findings lend credence to the idea that the burden of malaria in early-life results in sustained CNS changes that could contribute to increased vulnerability to adult-onset neuronal insults.
中文翻译：
幼年轻度疟疾病史会加剧小鼠慢性压力诱发的焦虑样行为、神经炎症和成年海马神经发生的衰退
居住在疟疾高发地区的儿童特别容易感染疟疾。这个生命早期窗口也是神经系统发育和成熟的关键时期，在此期间的炎症性损伤可能会引起精神病理学脆弱性的持续增加。我们在寄生虫清除后 60 天开始采用两次击中的幼年轻度疟疾模型和为期两周的慢性不可预测轻度压力 (CUMS) 方案，以评估幼年感染史是否使小鼠倾向于情绪相关的行为改变和神经认知缺陷。我们发现有幼年疟疾 (AH/JMAL) 病史的成年小鼠表现出与 CUMS 相关的焦虑样行为增强，认知行为没有明显变化。相比之下，有成年疟疾病史的小鼠并没有表现出如此增强的应激脆弱性。在基线时，AH/JMAL 小鼠的海马齿状回亚区中的活化小胶质细胞增加。这伴随着增殖神经元祖细胞的减少，未成熟海马神经元的总数没有改变。CUMS 进一步加剧了这种神经炎症和神经源性下降。在 CUMS 后第 14 天，AH/JMAL 小鼠的海马显示出显着更高的小胶质细胞激活，并伴随祖细胞增殖和未成熟神经元数量的减少。综上所述，这些结果表明，幼年型轻度疟疾病史会在海马生态位内留下神经炎症标记，这可能导致成年期应激反应加剧。
更新日期：2020-11-01
中文翻译：
幼年轻度疟疾病史会加剧小鼠慢性压力诱发的焦虑样行为、神经炎症和成年海马神经发生的衰退
居住在疟疾高发地区的儿童特别容易感染疟疾。这个生命早期窗口也是神经系统发育和成熟的关键时期，在此期间的炎症性损伤可能会引起精神病理学脆弱性的持续增加。我们在寄生虫清除后 60 天开始采用两次击中的幼年轻度疟疾模型和为期两周的慢性不可预测轻度压力 (CUMS) 方案，以评估幼年感染史是否使小鼠倾向于情绪相关的行为改变和神经认知缺陷。我们发现有幼年疟疾 (AH/JMAL) 病史的成年小鼠表现出与 CUMS 相关的焦虑样行为增强，认知行为没有明显变化。相比之下，有成年疟疾病史的小鼠并没有表现出如此增强的应激脆弱性。在基线时，AH/JMAL 小鼠的海马齿状回亚区中的活化小胶质细胞增加。这伴随着增殖神经元祖细胞的减少，未成熟海马神经元的总数没有改变。CUMS 进一步加剧了这种神经炎症和神经源性下降。在 CUMS 后第 14 天，AH/JMAL 小鼠的海马显示出显着更高的小胶质细胞激活，并伴随祖细胞增殖和未成熟神经元数量的减少。综上所述，这些结果表明，幼年型轻度疟疾病史会在海马生态位内留下神经炎症标记，这可能导致成年期应激反应加剧。
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