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

•Acute elevations in IL-1β and IL-6 expression in Fmr1 knock out (KO) mice.•No differences detected in cytokine expression 24 h post-immune stimulation.•Fmr1 KO mice had increased BDNF expression compared to wild type (WT) mice.•No differences in astrocyte or microglial reactivity between genotypes....

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Published in:	Physiology & behavior Vol. 215; p. 112776
Main Authors:	Hodges, Samantha L., Nolan, Suzanne O., Tomac, Lindsay A., Muhammad, Ilyasah D.A., Binder, Matthew S., Taube, Joseph H., Lugo, Joaquin N.
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 01-03-2020
Subjects:	Adjuvants, Immunologic - pharmacology Animals Autism Behavior, Animal - drug effects Cytokines - biosynthesis Feeding Behavior - drug effects Fmr1 Fragile X Mental Retardation Protein - genetics Fragile X Syndrome - metabolism Fragile X Syndrome - pathology Fragile X Syndrome - psychology IL-1β IL-6 Immunity, Innate - drug effects Inflammation - chemically induced Inflammation - metabolism Innate immunity Lipopolysaccharides Mice Mice, Knockout Mutation - genetics Sickness Autism Innate immunity Sickness IL-1β IL-6 Fmr1
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Summary:	•Acute elevations in IL-1β and IL-6 expression in Fmr1 knock out (KO) mice.•No differences detected in cytokine expression 24 h post-immune stimulation.•Fmr1 KO mice had increased BDNF expression compared to wild type (WT) mice.•No differences in astrocyte or microglial reactivity between genotypes.•Lipopolysaccharide-induced sickness behavior was similar in Fmr1 KO and WT mice. Fragile 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 result 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 those with FXS 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 4 h post-treatment compared to WT mice, with no differences detected in any cytokines at baseline or between genotypes 24 h post-LPS administration. Fmr1 KO mice also had upregulated hippocampal BDNF gene expression 4 h post-treatment compared to WT mice, which was not dependent on LPS administration. There were no differences in hippocampal protein expression between genotypes in microglia (Iba1) or astrocyte (GFAP) reactivity. Further, both genotypes displayed the typical sickness response following LPS stimulation, demonstrated by a significant reduction in food burrowed by LPS-treated mice in a burrowing task. Additional investigation is critical to determine if the transient increases in cytokine expression could lead to long-term changes in downstream molecular signaling in FXS. [Display omitted]
ISSN:	0031-9384 1873-507X
DOI:	10.1016/j.physbeh.2019.112776