Esposito Pasquale, Gandelman Michelle, Rodriguez Cloudia, Liang Jacky, Ismail Nafissa
NISE Laboratory, School of Psychology, Faculty of Social Sciences, University of Ottawa, Ontario, K1N 6N5, Canada.
Brain and Mind Research Institute, University of Ottawa, Ottawa, Ontario, K1N 6N5, Canada.
Brain Behav Immun Health. 2022 Oct 28;26:100543. doi: 10.1016/j.bbih.2022.100543. eCollection 2022 Dec.
Exposure to stressors during puberty can cause enduring effects on brain functioning and behaviours related to neurodegeneration. However, the mechanisms underlying these effects remain unclear. The gut microbiome is a complex and dynamic system that could serve as a possible mechanism through which early life stress may increase the predisposition to neurodegeneration. Therefore, the current study was designed to examine the acute effects of pubertal antimicrobial and lipopolysaccharide (LPS) treatments on the cellular mechanisms associated with neurodegenerative disorders in male and female mice. At five weeks of age, male and female CD-1 mice received 200 μL of broad-spectrum antimicrobials or water, through oral gavage, twice daily for seven days. Mice received an intraperitoneal (i.p.) injection of either saline or LPS at 6 weeks of age (i.e., pubertal period). Sickness behaviours were recorded and mice were euthanized 8 h post-injection. Following euthanasia, brains and blood samples were collected. The results indicated that puberal antimicrobial and LPS treatment induced sex-dependent changes in biomarkers related to sickness behaviour, peripheral inflammation, intestinal permeability, and neurodegeneration. The findings suggest that pubertal LPS and antimicrobial treatment may increase susceptibility to neurodegenerative diseases later in life, particularly in males.
青春期暴露于应激源会对大脑功能以及与神经退行性变相关的行为产生持久影响。然而，这些影响背后的机制仍不清楚。肠道微生物群是一个复杂的动态系统，可能是早期生活应激增加神经退行性变易感性的一种潜在机制。因此，本研究旨在探讨青春期抗菌药物和脂多糖（LPS）处理对雄性和雌性小鼠神经退行性疾病相关细胞机制的急性影响。5周龄时，雄性和雌性CD-1小鼠通过口服灌胃，每天两次，连续7天接受200μL广谱抗菌药物或水。6周龄（即青春期）时，小鼠腹腔注射生理盐水或LPS。记录疾病行为，并在注射后8小时对小鼠实施安乐死。安乐死后，收集大脑和血液样本。结果表明，青春期抗菌药物和LPS处理诱导了与疾病行为、外周炎症、肠道通透性和神经退行性变相关生物标志物的性别依赖性变化。研究结果表明，青春期LPS和抗菌药物处理可能会增加日后患神经退行性疾病的易感性，尤其是在雄性小鼠中。
