Ye Ting, Wang Dan, Cai Zixuan, Tong Lijuan, Chen Zhuo, Lu Jiashu, Lu Xu, Huang Chao, Yuan Xiaomei
Department of Pharmacology, School of Pharmacy, Nantong University, 19# Qixiu Road, Nantong, 226001, Jiangsu, China.
Invasive Technology Department, Nantong First People's Hospital, The Second Affiliated Hospital of Nantong University, #6 North Road Hai'er Xiang, Nantong, 226001, Jiangsu, China.
Neuropharmacology. 2020 Aug 1;172:108132. doi: 10.1016/j.neuropharm.2020.108132. Epub 2020 May 12.
Previous studies have reported that macrophage-colony stimulating factor (M-CSF), a drug that is used to treat hematological system disease, can ameliorate chronic stress-induced depressive-like behaviors in mice. This indicates that M-CSF could be developed into a novel antidepressant. Here, we investigated the antidepressive properties of M-CSF, aiming to explore its potential values in depression treatment. Our results showed that a single M-CSF injection at the dose of 75 and 100 μg/kg, but not at 25 or 50 μg/kg, ameliorated chronic unpredictable stress (CUS)-induced depressive-like behaviors in mice at 5 h after the drug treatment. In a time-dependent experiment, a single M-CSF injection (100 μg/kg) was found to ameliorate the CUS-induced depressive-like behaviors in mice at 5 and 8 h, but not at 3 h, after the drug treatment. The antidepressant effect of the single M-CSF injection (100 μg/kg) in chronically-stressed mice persisted at least 10 days and disappeared at 14 days after the drug treatment. Moreover, 14 days after the first injection, a second M-CSF injection (100 μg/kg) still produced antidepressant effects at 5 h after the drug treatment in chronically-stressed mice who re-displayed depressive-like phenotypes. The antidepressant effect of M-CSF appeared to be mediated by the activation of the hippocampal microglia, as pre-inhibition of microglia by minocycline (40 mg/kg) or PLX3397 (290 mg/kg) pretreatment prevented the antidepressant effect of M-CSF in CUS mice. These results demonstrate that M-CSF produces rapid and sustained antidepressant effects via the activation of the microglia in the hippocampus in a dose- and time-dependent manner.
先前的研究报道，巨噬细胞集落刺激因子（M-CSF），一种用于治疗血液系统疾病的药物，可以改善慢性应激诱导的小鼠抑郁样行为。这表明M-CSF可以开发成一种新型抗抑郁药。在此，我们研究了M-CSF的抗抑郁特性，旨在探索其在抑郁症治疗中的潜在价值。我们的结果表明，单次注射剂量为75和100μg/kg的M-CSF，但不是25或50μg/kg，在药物治疗后5小时改善了慢性不可预测应激（CUS）诱导的小鼠抑郁样行为。在一项时间依赖性实验中，发现单次注射M-CSF（100μg/kg）在药物治疗后5小时和8小时改善了CUS诱导的小鼠抑郁样行为，但在3小时没有。单次注射M-CSF（100μg/kg）对慢性应激小鼠的抗抑郁作用至少持续10天，并在药物治疗后14天消失。此外，在首次注射14天后，第二次注射M-CSF（100μg/kg）在重新出现抑郁样表型的慢性应激小鼠中，在药物治疗后5小时仍产生抗抑郁作用。M-CSF的抗抑郁作用似乎是由海马小胶质细胞的激活介导的，因为用米诺环素（40mg/kg）或PLX3397（290mg/kg）预处理预先抑制小胶质细胞可阻止M-CSF对CUS小鼠的抗抑郁作用。这些结果表明，M-CSF通过以剂量和时间依赖性方式激活海马中的小胶质细胞产生快速和持续的抗抑郁作用。
