Endocrine Abstracts

Introduction: Recently, the immune hypothesis of depression has gained a new dimension because of inflammasomes. NLRP3 inflammasome is a protein complex and its activation leads to stimulation of the enzyme caspase 1 responsible for generation of active form of pro-inflammatory cytokines: IL-1 β and IL-18. Recently postulated ‘inflammasome theory of depression’ assumes that depression is based on a disturbance of the mechanisms regulating NLRP3 complexes and uncontrolled synthesis of IL-1β.

Aim: The aim of present study was to examine whether prenatal stress influence the inflammasome NLRP3 system (subunits: NLR, ASC, protease caspase-1) in the frontal cortex and hippocampus of adult rats offspring. Furthermore the impact of chronic antidepressant drug – tianeptine administration on the above-mentioned parameters were evaluated.

Methods: Pregnant rats were subjected to restraint stress. At 3 months of age, control and prenatally stressed rats were tested for behavioural changes in forced swimming test. After that male offspring were administered i.p. for 14 days with tianeptine or vehicle. The animals’ behaviour were tested again and rats were sacrificed. The protein level of all NLRP3 inflammasome subunits was determined by Western blot analyses.

Result: Prenatal stress procedure cause long-lasting behavioral alterations expressed as an increase in immobility and a decrease in swimming and climbing time measured in the forced swim test. Chronic treatment of tianeptine normalized all above-mentioned changes in prenatally stressed offspring. Prenatal stress procedure increased concentration of all NLRP3 subunits in frontal cortex. In hippocampus prenatal stress affected caspase-1 levels but had no effect on the other NLRP3 inflammasome subunits. Chronic tianeptine treatment attenuated all evoked by stress changes.

Conclusion: Prenatal stress procedure leads not only to persistent behavioral disturbances but also malfunction in brain NLRP3 inflammasone pathway. NLRP3 pathway can be indicate as an potential attractive target for antidepressant drug action.

Acknowledgement

Supported by the grant no. 2015/17/N/NZ7/00924.