Antidepressive properties of microglial stimulation in a mouse model of depression induced by chronic unpredictable stress.
Prog Neuropsychopharmacol Biol Psychiatry
; 101: 109931, 2020 07 13.
Article
em En
| MEDLINE
| ID: mdl-32201112
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.
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Base de dados:
MEDLINE
Assunto principal:
Estresse Psicológico
/
Microglia
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Depressão
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Modelos Animais de Doenças
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Antidepressivos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Prog Neuropsychopharmacol Biol Psychiatry
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
China