Yahfoufi Nour, Ah-Yen Emily G, Chandrasegaram Rajini, Aly Sarah, Murack Michael, Kadamani Anthony K, Matar Chantal, Ismail Nafissa
Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ontario, Canada.
NISE Laboratory, School of Psychology, Faculty of Social Sciences, University of Ottawa, Ontario, Canada.
Compr Psychoneuroendocrinol. 2021 Jun 5;7:100063. doi: 10.1016/j.cpnec.2021.100063. eCollection 2021 Aug.
Adolescence is a critical period of development during which the brain undergoes significant remodeling that impacts behavior later in life. Exposure to stress, and especially immune challenge, during this period triggers changes in brain function resulting in the development of mental disorders in adulthood, such as depression and anxiety. Previous studies from our laboratory have shown that a single exposure to LPS (lipopolysaccharide) during puberty causes enduring depression-like behaviour in females and anxiety-like behaviours in males. However, administration of probiotics during puberty blocked the enduring effects of LPS on depression-like and anxiety-like behaviors in female and male mice, respectively. These results suggest that the gut microbiome is a mediator of the effects of stress on mental health. The objective of the current study is to examine the effectiveness of a novel probiotic subsp. in blocking LPS-induced anxiety-like and depression-like behaviors in adult male and female mice. Our results showed that subsp. blocked LPS-induced depression-like behavior in female mice. We also found that pubertal treatment with subsp. mitigated the LPS-induced decrease in 5HT1A expression in CA1 as well as the LPS-induced increase in 5HT1A expression in the raphe-nuclei in female mice. Contrary to our predictions, pubertal LPS treatment at 6 weeks of age did not induce enduring anxiety-like behavior in males. There was also no difference in anxiety-like behavior between the LPS-sucrose and LPS-probiotic male groups. However, pubertal LPS treatment increased the expression of 5HT1A receptors in the DRN in males, while probiotic exposure mitigated this increase. Our study highlights the consequences of stress exposure (immune challenge) on mental health in adulthood taking into consideration 5HT1A receptors expression at different regions of the brain. It also emphasizes on the importance of considering adolescence as window of opportunities during which probiotic use can alleviate the long-term neural and behavioral alterations induced by stress.
青春期是一个关键的发育时期，在此期间大脑会经历显著的重塑，这会影响日后的行为。在这个时期接触压力，尤其是免疫挑战，会引发大脑功能的变化，导致成年后出现精神障碍，如抑郁症和焦虑症。我们实验室之前的研究表明，青春期单次接触脂多糖（LPS）会使雌性出现持久的抑郁样行为，使雄性出现焦虑样行为。然而，青春期给予益生菌分别阻断了LPS对雌性和雄性小鼠抑郁样和焦虑样行为的持久影响。这些结果表明，肠道微生物群是压力对心理健康影响的介导者。本研究的目的是检验一种新型益生菌亚种在阻断成年雄性和雌性小鼠LPS诱导的焦虑样和抑郁样行为方面的有效性。我们的结果表明，该亚种阻断了雌性小鼠LPS诱导的抑郁样行为。我们还发现，青春期用该亚种治疗可减轻LPS诱导的雌性小鼠CA1区5HT1A表达降低以及LPS诱导的中缝核5HT1A表达增加。与我们的预测相反，6周龄时青春期LPS处理并未在雄性中诱导出持久的焦虑样行为。LPS-蔗糖组和LPS-益生菌组雄性小鼠在焦虑样行为方面也没有差异。然而，青春期LPS处理增加了雄性小鼠中脑导水管周围灰质中5HT1A受体的表达，而益生菌暴露减轻了这种增加。我们的研究强调了考虑到大脑不同区域5HT1A受体表达的情况下，压力暴露（免疫挑战）对成年后心理健康的影响。它还强调了将青春期视为一个机会窗口的重要性，在此期间使用益生菌可以减轻压力诱导的长期神经和行为改变。
