Paliperidone attenuates chronic stress-induced changes in the expression of inflammasomes-related protein in the frontal cortex of male rats

Several stress-related neuropsychiatric diseases are related to inflammatory phenomena. Thus, a better understanding of stress-induced immune responses could lead to enhanced treatment alternatives. Little is known about the possible involvement of inflammasomes in the stress-induced proinflammatory response. Antipsychotics have anti-inflammatory effects, but the possible antipsychotic treatment actions on inflammasomes remain unexplored. Our aim was to study whether inflammasomes are involved in the neuroinflammation induced by a paradigmatic model of chronic stress and whether the monoamine receptor antagonist paliperidone can modulate the possible stress-induced inflammasomes activation in the frontal cortex (FC). Thus, the effects of paliperidone (1 mg/Kg, oral gavage) administered during a chronic restraint stress protocol (6 h/day for 21 days) on the possible stress-related inflammasomes protein induction were evaluated through Western blot in the FC of male Wistar rats. Stress increased protein expression levels of the inflammasome complexes NALP1, NLRP3 and AIM2 and augmented caspase-1 and mature interleukin (IL)-1 beta protein levels. Paliperidone pre-treatment normalized the protein expression of the inflammasome pathway. In conclusion, our data indicate an induction of inflammasome complexes by chronic restraint stress in the FC of rats. The antipsychotic paliperidone has an inhibitory action on some of the stress-induced inflammasomes stimulation trying to normalize the neuroinflammatory scenario caused by stress. Considering the emerging role of inflammation in neuropsychiatric diseases, the development of new drugs targeting inflammasome pathways is a promising approach for future therapeutic interventions.

Automated summary

This study investigated the potential involvement of inflammasomes in stress-induced neuroinflammation and the modulatory effects of paliperidone. The findings suggest that chronic stress induces inflammasome complexes in the frontal cortex of rats, and pre-treatment with paliperidone can normalize this response, highlighting its inhibitory action on stress-induced inflammasomes. Targeting inflammasome pathways could be a promising approach for future therapeutic interventions in neuropsychiatric diseases.