No NLRP3 Inflammasome Expression in the Ouabain Animal Model of Bipolar Disorder

Abstract

Introduction Inflammation is believed to play a role in both bipolar illness and unipolar depression. Markers of inflammation are elevated during acute mood episodes. Specifically, gene expressions of the nucleotide-binding domain and leucine-rich repeat pyrin domain containing 3 (NLRP3)-related proteins in peripheral blood have been purported to be upregulated in patients with bipolar disorder. We examined the elaboration of NLRP3 in the ouabain animal model of bipolar disorder. Methods The frontal cortex, hippocampus, and basal ganglia tissue from young, male Sprague-Dawley rats who received intracerebroventricular (ICV) ouabain as a model of bipolar disorder or artificial cerebrospinal fluid (aCSF) were examined for NLRP3 utilizing protein immunoblot (Western) analysis. Results We could not demonstrate any NLRP3 in rat brain, but NLRP3 was detected in control from mouse brain and lung. Discussion This study demonstrates that the manifestation of manic behavior in rats treated with ICV ouabain is not accompanied by elaboration of NLRP3 inflammasome. This raises the question of the primacy of inflammation in the pathophysiology of mania. If these findings are reproduced in this and other animal models of mania, they would raise important questions about whether inflammation is a primary or secondary phenomenon in the brains of subjects with bipolar disorder.

Keywords: brain; nlrp3-inflammasome; ouabain; ouabain model of mania.

Figure 1. The house-keeping protein glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was present in all samples.

Positive control A549 cell line showed expression of NLRP3 at 110 kD when run with samples from the frontal cortex (FC), basal ganglia (BG), and hippocampus (Hip). None of the three control rats (aCSF) or the three ouabain-treated rats (OB) showed expression of NLRP3.

Figure 2. The NLRP3 expression is much lower in the brain tissue of short-time frozen mouse samples compared to lung tissue.

FC: frontal cortex;  BG: basal ganglia;  Hip: hippocampus; NLRP3: nod-like receptor pyrin containing 3 or nucleotide-binding domain, leucine-rich repeat, pyrin domain containing 3; GAPDH: glyceraldehyde-3-phosphate dehydrogenase