NISE Laboratory, School of Psychology, Faculty of Social Sciences, University of Ottawa, Ontario K1N 6N5, Canada.
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; LIFE Research Institute, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada.
Horm Behav. 2024 Sep;165:105615. doi: 10.1016/j.yhbeh.2024.105615. Epub 2024 Aug 17.
Exposure to stressors during puberty can disrupt normal development and possibly increase susceptibility to neurodegenerative disorders later in life. However, the mechanisms underlying the relationship between pubertal stress exposure and neurodegeneration remain unclear. As such, the current study was designed to examine the effects of pubertal antimicrobial (AMNS) and lipopolysaccharide (LPS) treatments on intestinal and blood-brain-barrier (BBB) permeability in male and female mice. Moreover, we also examined the sex-specific effects of pubertal AMNS and LPS treatments on gross motor activity, heart rate, and core body temperature. At four weeks of age, male and female CD1 mice were implanted with the G2 HR E-Mitter telemetry system. At five weeks of age, mice received 200 μL of broad-spectrum antimicrobial or water, through oral gavage, twice daily for seven days. Mice received an intraperitoneal injection of either saline or LPS at six weeks of age. BBB and intestinal permeability were examined 24 h, 72 h, and one week post-LPS/saline treatment. Telemetric data was collected for 48 h post-LPS/saline treatment. The results showed that pubertal AMNS and LPS treatments increased sickness behaviours and decreased body temperature and heart rate, in a sex-dependent manner. Furthermore, pubertal AMNS and LPS treatments resulted in sex-dependent regional increases in BBB permeability 24 h and 72 h post-LPS/saline treatment, while global increases in BBB permeability were only observed one week post-LPS/saline treatment. These results further our understanding of the combined effects of AMNS and LPS treatments on physiology and on the enduring negative changes observed following pubertal exposure to stressors.
青春期暴露于应激源会干扰正常发育，并可能增加日后患神经退行性疾病的易感性。然而，青春期应激暴露与神经退行性变之间的关系的机制仍不清楚。因此，本研究旨在研究青春期抗微生物（AMNS）和脂多糖（LPS）处理对雄性和雌性小鼠肠道和血脑屏障（BBB）通透性的影响。此外，我们还研究了青春期 AMNS 和 LPS 处理对雄性和雌性小鼠的总运动活动、心率和核心体温的性别特异性影响。在四周龄时，雄性和雌性 CD1 小鼠植入 G2 HR E-Mitter 遥测系统。在五周龄时，小鼠通过口服灌胃每天两次接受 200μL 广谱抗微生物或水，共七天。在六周龄时，小鼠接受腹腔内注射生理盐水或 LPS。在 LPS/生理盐水处理后 24、72 和一周时检查 BBB 和肠道通透性。在 LPS/生理盐水处理后 48 小时收集遥测数据。结果表明，青春期 AMNS 和 LPS 处理以性别依赖的方式增加了疾病行为，降低了体温和心率。此外，青春期 AMNS 和 LPS 处理导致 LPS/生理盐水处理后 24 小时和 72 小时 BBB 通透性的性别依赖性区域增加，而仅在 LPS/生理盐水处理后一周观察到 BBB 通透性的全局增加。这些结果进一步了解了 AMNS 和 LPS 处理对生理的综合影响，以及青春期暴露于应激源后观察到的持久的负面变化。
