Antidepressive properties of microglial stimulation in a mouse model of depression induced by chronic unpredictable stress.
The decrease of microglia in the hippocampus is a novel mechanism for depression onset. Reversal of this decrease can ameliorate stress-induced depression-like behaviors in rodents. However, the property of this therapeutic strategy remains unclear. We addressed this issue by designing a series of behavioral experiments. Results showed that a single lipopolysaccharide (LPS) injection at the dose of 75 and 100 μg/kg, but not at 30 or 50 μg/kg, produced obvious antidepressant effects in chronic unpredictable stress (CUS) mice at 5 h after the drug administration. In the time-dependent experiment, a single LPS injection (100 μg/kg) ameliorated the CUS-induced depression-like behaviors in mice at 5 and 8 h, but not at 3 h, after the drug administration. The antidepressant effect of a single LPS injection persisted at least 10 days and disappeared at 14 days after the drug administration. 14 days after the first injection, a second LPS injection (100 μg/kg) still produced antidepressant effects in chronically-stressed mice who re-displayed depression-like behaviors at 5 h after the drug administration. The antidepressant effect of LPS appears to be dependent on microglia, as at 5 h after LPS administration (100 μg/kg), the CUS-induced decrease in microglial numbers and Iba-1 mRNA levels in the hippocampus was reversed markedly, and inhibition of microglia by minocycline (40 mg/kg) or PLX33297 (290 mg/kg) prevented the antidepressant effect of LPS in CUS mice. These results indicate that a single LPS injection displays rapid and sustained antidepressant effects in chronically stressed mice likely through stimulating hippocampal microglia.
['Cai|Zixuan|Z|', 'Ye|Ting|T|', 'Xu|Xing|X|', 'Gao|Minhui|M|', 'Zhang|Yaru|Y|', 'Wang|Dan|D|', 'Gu|Yiming|Y|', 'Zhu|Haojie|H|', 'Tong|Lijuan|L|', 'Lu|Jiashu|J|', 'Chen|Zhuo|Z|', 'Huang|Chao|C|']
D000818:Animals D000928:Antidepressive Agents D003863:Depression D004195:Disease Models, Animal D004305:Dose-Response Relationship, Drug D007103:Immobilization D008070:Lipopolysaccharides D008297:Male D051379:Mice D008810:Mice, Inbred C57BL D017628:Microglia D008911:Minocycline D013315:Stress, Psychological
Depression Microglia Lipopolysaccharide Minocycline PLX3397