Role of Chronic Administration of Antidepressant Drugs in the Prenatal Stress-Evoked Inflammatory Response in the Brain of Adult Offspring Rats: Involvement of the NLRP3 Inflammasome-Related Pathway.

Abstract:

:Evidence indicates that adverse experiences in early life may be a factor for immune disturbances leading to the depression in adulthood. Recently, a pivotal role in the pathogenesis of depression has been assigned to the activation of the brain Nod-like receptor pyrin-containing 3 (NLRP3) inflammasome. We investigated the impact of chronic treatment with antidepressant drugs on the behavioral disturbances and the levels of proinflammatory factors in the hippocampus and frontal cortex of adult male rats after prenatal stress exposure. Next, we explored the involvement of the NLRP3 inflammasome-related pathways in the mechanism of antidepressant action. Our study confirmed that chronic antidepressant treatment attenuated depression-like disturbances and exerted an anxiolytic action. All antidepressants diminished the prenatal stress-induced increase in IL-1β in both brain areas, while IL-18 only in the hippocampus. Moreover, tianeptine administration diminished the increase in CCR2 levels in both brain areas, while in the hippocampus, tianeptine, along with venlafaxine CCL2 and iNOS levels. Next, we observed that in the hippocampus, tianeptine and fluoxetine suppressed upregulation of TLR4. Furthermore, venlafaxine suppressed NFкB p65-subunit phosphorylation, while fluoxetine enhanced the IкB level. Importantly, in the hippocampus, all antidepressants normalized evoked by stress changes in caspase-1 level, while tianeptine and venlafaxine also affect the levels of ASC and NLRP3 subunits. Our results provide new evidence that chronic administration of antidepressants exerts anti-inflammatory effects more pronounced in the hippocampus, through suppression of the NLRP3 inflammasome activation. These effects are accompanied by an improvement in the behavioral dysfunctions evoked by prenatal stress.

journal_name

Mol Neurobiol

journal_title

Molecular neurobiology

authors

Trojan E,Chamera K,Bryniarska N,Kotarska K,Leśkiewicz M,Regulska M,Basta-Kaim A

doi

10.1007/s12035-018-1458-1

subject

Has Abstract

pub_date

2019-08-01 00:00:00

pages

5365-5380

issue

8

eissn

0893-7648

issn

1559-1182

pii

10.1007/s12035-018-1458-1

journal_volume

56

pub_type

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