1. Academic Validation
  2. Antidepressive properties of microglial stimulation in a mouse model of depression induced by chronic unpredictable stress

Antidepressive properties of microglial stimulation in a mouse model of depression induced by chronic unpredictable stress

  • Prog Neuropsychopharmacol Biol Psychiatry. 2020 Jul 13;101:109931. doi: 10.1016/j.pnpbp.2020.109931.
Zixuan Cai 1 Ting Ye 1 Xing Xu 1 Minhui Gao 2 Yaru Zhang 1 Dan Wang 1 Yiming Gu 1 Haojie Zhu 1 Lijuan Tong 1 Jiashu Lu 3 Zhuo Chen 4 Chao Huang 5
Affiliations

Affiliations

  • 1 Department of Pharmacy, School of Pharmacy, Nantong University, #19 Qixiu Road, Nantong 226001, Jiangsu Province, China.
  • 2 Department of Pharmacology, Nantong Health College of Jiangsu Province, #288 Zhenxing East Road, Nantong 226010, Jiangsu Province, China.
  • 3 Department of Pharmacy, The People's Hospital of Taizhou, The Fifth Affiliated Hospital of Nantong University, #210 Yingchun Road, Taizhou 225300, Jiangsu, China.
  • 4 Invasive Technology Department, Nantong First People's Hospital, The Second Affiliated Hospital of Nantong University, #6 North Road Hai'er Xiang, Nantong 226001, Jiangsu Province, China.
  • 5 Department of Pharmacy, School of Pharmacy, Nantong University, #19 Qixiu Road, Nantong 226001, Jiangsu Province, China. Electronic address: huachao@ntu.edu.cn.
Abstract

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.

Keywords

Depression; Lipopolysaccharide; Microglia; Minocycline; PLX3397.

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