Journal
NEUROPHARMACOLOGY
Volume 193, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2021.108621
Keywords
Innate immune activation; Macrophage-colony stimulating factor; Prevention; Neuroinflammation
Categories
Funding
- Natural Science Foundation of China [81771467, 81974216, 31771172]
- Natural Science Foundation of Jiangsu Province [BK20180267, BK20191207]
- Science and Technology Project of Nantong City [JC2019071, JC2020020]
- Six Talent Peaks Project in Jiangsu Province [SWYY-071]
- Natural Science Foundation of the Higher Education Institutions of Jiangsu Province [20KJB310025]
- postgraduate research and practice innovation program of Jiangsu Province [KYCX20-2855]
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The study demonstrated that M-CSF preconditioning can alleviate stress-induced depression-like behaviors by modulating neuroinflammatory responses.
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.
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