Chronic mild stress-induced anhedonia in rats is coupled with the upregulation of inflammasome sensors: a possible involvement of NLRP1

INTRODUCTION: NOD-like receptors containing pyrin domain (NLRP) are cytosolic receptors belong to innate immune system and function as sensing bodies for danger signals by forming inflammasome complex which in turn produces caspase-1-mediated interleukin (IL)-1β and IL-18 proinflammatory cytokines. Latest findings indicate that NLRP3 inflammasome mainly located in microglia cells in central nervous system (CNS) is linked to depression pathophysiology. However, another important CNS inflammasome, the neuronal NLRP1 inflammasome, has not been addressed in psychological stress or depression, yet. Therefore, the aim of the present study was to investigate the possible involvement NLRP1 inflammasome together with NLRP3 in chronic unpredictable mild stress (CUMS), a well-validated animal model of depression in rats. METHODS: Adult male Sprague–Dawley rats were divided into three groups: Control (treated with saline; non-stressed), CUMS (treated with saline), and CUMS + IMI (Imipramine; 10 mg/kg/day) (n = 6–8/group). In CUMS model, various stressors were applied for a total duration of six weeks. The treatments were daily administered via intraperitoneal (i.p.) route for the last three weeks of CUMS procedure. Anhedonia-like behaviors were assessed by sucrose preference test once in every two weeks throughout the experiment. At the end of the sixth week, rats were sacrificed and hippocampal brain tissues were collected for real-time PCR gene expression analysis of inflammasome components (NLRP1, NLRP3, ASC, and caspase-1) and inflammasome-dependent two proinflammatory cytokines (IL-1β and IL-18). RESULTS: CUMS-induced anhedonia in rats was coupled with upregulated mRNA levels of NLRP1, NLRP3, ASC, caspase-1, IL-1β, and IL-18 in hippocampus which were downregulated by chronic imipramine treatment. CONCLUSIONS: Our results suggest that the activation of not only NLRP3 but also NLRP1 inflammasome together may be involved in chronic stress-induced depression. Based on these results, further investigations are of great importance in order to understand the possible crosstalk between microglial (NLRP3) and neuronal (NLRP1) inflammasomes in depression and psychological stress

Serum Immunoglobulin G of Neuro-Behçet’s Disease Patients Reduce Cerebral Expression Levels of Survival Pathway Factors

Objective: Anti-neuronal antibodies are found in sera of neuro-Behçet’sdisease (NBD) patients. In this study, our aim was to analyze the potentialmechanisms by which NBD immunoglobulin (Ig) Gs affect neuronaldysfunction. Materials and Methods: Purified IgGs obtained from pooledsera of six each NBD patients and healthy controls (HCs) were administeredto Sprague Dawley rats through intraventricular injection. Control rats receivedphosphate-buffered saline (PBS) only. Locomotor activity was assessed byopen field test on days 0, 10, and 25. Cerebral expression levels of intracellularpathway factors associated with cell survival and viability were measured byreal-time polymerase chain reaction. Results: Rats treated with NBD IgGexhibited reduced motor activity. On day 25, the mean number of crossings was44 ± 7, 90 ± 12, and 93 ± 5 and the mean number of rearings was 18 ± 7,34 ± 5, and 35 ± 6 for NBD IgG, HC IgG, and PBS groups, respectively(P < 0.001). Relative expression levels of Akt-1 (0.4 ± 0.2, 1.0 ± 0.3, and0.9 ± 0.6; P = 0.004), DJ-1 (0.6 ± 0.2, 1.0 ± 0.6, and 0.9 ± 0.5; P = 0.047),mouse double mininute-2 (0.5 ± 0.3, 0.9 ± 0.2, and 1.0 ± 0.2; P = 0.002), andmechanistic target of rapamycin (0.4 ± 0.2, 0.8 ± 0.4, and 0.9 ± 0.6; P = 0.006)were significantly lower in NBD-IgG group than HC IgG and PBS groups. Bycontrast, the expression levels of factors associated with apoptosis (caspase 3,mitochondrial carrier homolog 1, and B-cell lymphoma-2) were comparableamong different treatment arms. Conclusion: Our results suggest that at least afraction of NBD IgG interacts with neuronal surface antigens and subsequentlydecreases neuronal viability through Akt pathway inhibition. By contrast, NBDIgG does not appear to activate neuronal apoptosis. Further identification of thebinding sites of serum IgG ıs required

Antidepressant-like effects induced by chronic blockade of the purinergic 2X7 receptor through inhibition of non-like receptor protein 1 inflammasome in chronic unpredictable mild stress model of depression in rats

Objective: Purinergic 2X7 receptor (P2X7R) activation is known to be involved in pathogenesis of depression. Our aims were to investigate P2X7R-activated inflammasome pathways in parallel with induction of depression and to test the antidepressant-like effects of the selective P2X7R antagonist Brilliant Blue G (BBG) in a rat model of chronic unpredictable mild stress (CUMS)