Innate immune tolerance against adolescent intermittent alcohol exposure-induced behavioral abnormalities in adult mice.
Innate immune tolerance against adolescent intermittent alcohol exposure-induced behavioral abnormalities in adult mice.
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DOI：
10.1016/j.intimp.2022.109250
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发表时间：
2022-10
影响因子：
5.6
通讯作者：
Minxiu Ye;H. Xiang;Huijun Liu;Zhichao Hu;Yue Wang;Yue Gu;Xu Lu;Chao Huang
中科院分区：
文献类型：
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作者：
Minxiu Ye;H. Xiang;Huijun Liu;Zhichao Hu;Yue Wang;Yue Gu;Xu Lu;Chao Huang
据报道，预先刺激动物的先天免疫系统可以预防动物的慢性应激诱导的抑郁和焦虑样行为，这表明先天免疫刺激剂可能预防神经精神疾病的发病机制。饮酒，尤其是在青春期开始饮酒，是成年后发生神经精神疾病的危险因素。预防青少年期酒精暴露引起的病理变化对改善人类心理健康具有重要意义。在此，我们研究了先天免疫系统的预刺激是否可以预防青少年间歇性酒精暴露（AIE）引起的疾病模型中的行为异常。结果表明，在酒精暴露前1d一次性注射脂多糖（LPS）（100 μg/kg），可预防AIE所致成年小鼠悬尾实验、强迫游泳实验、蔗糖偏好实验、高架十字迷宫实验、光暗实验和旷场实验中的抑郁和焦虑样行为。在酒精暴露前单次注射LPS（100 μg/kg）也将成年小鼠海马和前额皮质中AIE诱导的神经炎症反应转化为抗炎表型。米诺环素预处理抑制先天免疫反应取消了LPS对成年小鼠海马和前额皮质AIE诱导的异常和神经炎症反应的预防作用。这些结果表明，先天免疫系统的预刺激可以通过预防神经炎症来预防成年小鼠中AIE诱导的抑郁和焦虑样行为。这可能有助于开发新的策略，以防止青少年酒精暴露引起的神经精神疾病。
It has been reported that pre-stimulation of the innate immune system in animals can prevent chronic stress-induced depression- and anxiety-like behaviors in animals, suggesting the possibility that innate immune stimulants may prevent the pathogenesis of neuropsychiatric disorders. Alcohol use, especially when it begins in adolescence, is a risk factor for the development of neuropsychiatric disorders in adulthood. Preventing the pathological changes induced by alcohol exposure in adolescence could be of great importance for improving human mental health. Here, we investigated whether pre-stimulation of the innate immune system can prevent the behavioral abnormalities in a disease model induced by adolescent intermittent alcohol exposure (AIE). The results showed that a single injection of lipopolysaccharide (LPS) injection (100 μg/kg) one day before alcohol exposure prevented the AIE-induced depression- and anxiety-like behaviors in the tail suspension test, forced swimming test, sucrose preference test, elevated pluz maze test, light–dark test, and open field test in adult mice. Single LPS injection (100 μg/kg) before alcohol exposure also transformed the AIE-induced neuroinflammatory responses in the hippocampus and prefrontal cortex in adult mice to an anti-inflammatory phenotype. Suppression of the innate immune response by minocycline pretreatment abolished the preventive effect of LPS on AIE-induced abnormalities and neuroinflammatory responses in the hippocampus and prefrontal cortex in adult mice. These results indicate that pre-stimulation of the innate immune system may prevent the AIE-induced depression- and anxiety-like behaviors in adult mice by preventing neuroinflammation. This may help to develop new strategies to prevent neuropsychiatric disorders induced by adolescent alcohol exposure.