A prophylactic effect of macrophage-colony stimulating factor on chronic stress-induced depression-like behaviors in mice
A prophylactic effect of macrophage-colony stimulating factor on chronic stress-induced depression-like behaviors in mice
复制标题
巨噬细胞集落刺激因子对小鼠慢性应激诱发的抑郁样行为的预防作用
DOI：
10.1016/j.neuropharm.2021.108621
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发表时间：
2021-06-03
影响因子：
4.7
通讯作者：
Huang, Chao
中科院分区：
文献类型：
--
作者：
Ji, Jianlin;Xiang, Haitao;Huang, Chao
先天免疫激活已被证明可以减轻神经系统疾病的严重程度，如脑缺血和创伤性脑损伤。巨噬细胞集落刺激因子（M-CSF）是一种用于治疗血液系统疾病的药物，是先天免疫反应的增强剂。在本研究中，我们评估了M-CSF预处理对小鼠慢性社会失败应激（CSDS）诱导的抑郁样行为的影响。结果表明，在应激暴露前1天单次注射100和500 μ g/kg剂量的M-CSF，或在应激暴露前1天或5天单次注射100 μ g/kg剂量的M-CSF，可阻止应激暴露前10天单次注射100 μ g/kg剂量的M-CSF诱导的小鼠抑郁样行为。进一步分析表明，在第一次注射M-CSF后10天注射第二次M-CSF，以及在应激暴露前10天注射2次或4次M-CSF，也可以预防csds诱导的抑郁样行为。分子研究表明，应激暴露前单次M-CSF注射使csds暴露小鼠大脑中的神经炎症反应向抗炎表型倾斜。M-CSF的这些行为和分子作用与先天免疫刺激相关，因为米诺环素预处理（40 mg/kg）预先抑制先天免疫激活可以消除M-CSF对csds诱导的抑郁样行为和神经炎症反应的预防作用。这些结果提供了证据，表明M-CSF预处理的先天免疫激活可能通过阻止大脑神经炎症反应的发展来预防慢性应激诱导的抑郁样行为，这可能有助于开发预防抑郁症的新策略。
Innate immune activation has been shown to reduce the severity of nervous system disorders such as brain ischemia and traumatic brain damage. Macrophage-colony stimulating factor (M-CSF), a drug that is used to treat hematological system disease, is an enhancer of the innate immune response. In the present study, we evaluated the effect of M-CSF preconditioning on chronic social defeat stress (CSDS)-induced depression-like behaviors in mice. Results showed that a single M-CSF injection 1 day before stress exposure at the dose of 100 and 500 mu g/kg, or a single M-CSF injection (100 mu g/kg) 1 or 5 days but not 10 days before stress exposure prevented CSDSinduced depression-like behaviors in mice. Further analysis showed that a second M-CSF injection 10 days after the first M-CSF injection and a 2 x or 4 x M-CSF injections 10 days before stress exposure also prevented CSDS-induced depression-like behaviors. Molecular studies revealed that a single M-CSF injection prior to stress exposure skewed the neuroinflammatory responses in the brain in CSDS-exposed mice towards an antiinflammatory phenotype. These behavioral and molecular actions of M-CSF were correlated with innate immune stimulation, as pre-inhibiting the innate immune activation by minocycline pretreatment (40 mg/kg) abrogated the preventive effect of M-CSF on CSDS-induced depression-like behaviors and neuroinflammatory responses. These results provide evidence to show that innate immune activation by M-CSF pretreatment may prevent chronic stress-induced depression-like behaviors via preventing the development of neuroinflammatory response in the brain, which may help to develop novel strategies for the prevention of depression.