Lipopolysaccharide-induced inflammation leads to acute elevations in pro-inflammatory cytokine expression in a mouse model of Fragile X syndrome

Publication date: Available online 12 December 2019Source: Physiology & BehaviorAuthor(s): Samantha L. Hodges, Suzanne O. Nolan, Lindsay A. Tomac, Ilyasah D.A. Muhammad, Matthew S. Binder, Joseph H. Taube, Joaquin N. LugoAbstractFragile X syndrome (FXS) is a neurodevelopmental disorder caused by a single genetic mutation in the Fmr1 gene, serving as the largest genetic cause of intellectual disability. Trinucleotide expansion mutations in Fmr1 results in silencing and hypermethylation of the gene, preventing synthesis of the RNA binding protein Fragile X mental retardation protein which functions as a translational repressor. Abnormal immune responses have been demonstrated to play a role in FXS pathophysiology, however, whether these alterations impact how they respond to an immune insult behaviorally is not entirely known. In the current study, we examine how Fmr1 knockout (KO) and wild type (WT) mice respond to the innate immune stimulus lipopolysaccharide (LPS), both on a molecular and behavioral level, to determine if Fmr1 mutations impact the normal physiological response to an immune insult. In response to LPS, Fmr1 KO mice had elevated hippocampal IL-1β and IL-6 mRNA levels 4hrs. post-treatment compared to WT mice, with no differences detected in any cytokines at baseline or between genotypes 24hrs. post-LPS administration. Fmr1 KO mice also had upregulated hippocampal BDNF gene expression 4hrs. post-injections compared to WT mice, which was not dependent on LPS admi...
Source: Physiology and Behavior - Category: Physiology Source Type: research