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Tolerance-inducing effect and properties of innate immune stimulation on chronic stress-induced behavioral abnormalities in mice.
- Source :
-
Brain, Behavior & Immunity . Jan2021, Vol. 91, p451-471. 21p. - Publication Year :
- 2021
-
Abstract
- • LPS preconditioning prevents CSDS-induced behavioral abnormalities in mice. • 10-days interval abolishes the effect of LPS on behavioral abnormalities. • A second LPS injection produces prophylactic effect on behavioral abnormalities. • Repeated LPS injection prior to stress exposure prevents behavioral abnormalities. • Microglial inhibition blocks the effect of LPS on behavioral abnormalities. Over-activation of the innate immune system constitutes a risk factor for the development of nervous system disorders but may reduce the severity of these disorders by inducing tolerance effect. Here, we studied the tolerance-inducing effect and properties of innate immune stimulation on chronic social defeat stress (CSDS)-induced behavioral abnormalities in mice. A single injection of the innate immune enhancer lipopolysaccharide (LPS) one day before stress exposure prevented CSDS-induced impairment in social interaction and increased immobility time in the tail suspension test and forced swimming test. This effect was observed at varying doses (100, 500, and 1000 μg/kg) and peaked at 100 μg/kg. A single LPS injection (100 μg/kg) either one or five but not ten days before stress exposure prevented CSDS-induced behavioral abnormalities. A second LPS injection ten days after the first LPS injection, or a 2 × or 4 × LPS injections ten days before stress exposure also induced tolerance against stress-induced behavioral abnormalities. Our results furthermore showed that a single LPS injection one day before stress exposure skewed the neuroinflammatory response in the hippocampus and prefrontal cortex of CSDS-exposed mice toward an anti-inflammatory phenotype. Inhibiting the central innate immune response by pretreatment with minocycline or PLX3397 abrogated the tolerance-inducing effect of LPS preconditioning on CSDS-induced behavioral abnormalities and neuroinflammatory responses in the brain. These results provide evidence for a prophylactic effect of innate immune stimulation on stress-induced behavioral abnormalities via changes in microglial activation, which may help develop novel strategies for the prevention of stress-induced psychological disorders. [ABSTRACT FROM AUTHOR]
- Subjects :
- *HUMAN abnormalities
*PREFRONTAL cortex
*HIPPOCAMPUS (Brain)
*NERVOUS system
*MICE
Subjects
Details
- Language :
- English
- ISSN :
- 08891591
- Volume :
- 91
- Database :
- Academic Search Index
- Journal :
- Brain, Behavior & Immunity
- Publication Type :
- Academic Journal
- Accession number :
- 147622799
- Full Text :
- https://doi.org/10.1016/j.bbi.2020.11.002