The brain expression of genes involved in inflammatory response, the ribosome, and learning and memory is altered by centrally injected lipopolysaccharide in mice

Abstract

Neuroinflammation plays a role in the progression of several neurodegenerative disorders. We used a lipopolysaccharide (LPS) model of neuroinflammation to characterize the gene expression changes underlying the inflammatory and behavioral effects of neuroinflammation. A single intracerebroventricular injection of LPS (5 µg) was administered into the lateral ventricle of mice and, 24 hours later, we examined gene expression in the cerebral cortex and hippocampus using microarray technology. Gene Ontology (GO) terms for inflammation and the ribosome were significantly enriched by LPS, whereas GO terms associated with learning and memory had decreased expression. We detected 224 changed transcripts in the cerebral cortex and 170 in the hippocampus. Expression of Egr1 (also known as Zif268) and Arc, two genes associated with learning and memory, was significantly lower in the cortex, but not hippocampus, of LPS-treated animals. Overall, altered expression of these genes may underlie some of the inflammatory and behavioral effects of neuroinflammation.

Inflammation Triggers Synaptic Alteration and Degeneration in Experimental Autoimmune Encephalomyelitis

“…This alteration was responsible for synaptic degeneration in this model and support the emerging notion that the neuronal compartment of the CNS suffers in parallel and even independently of white matter damage in MS. Abnormal glutamate transmission involved AMPA receptors and were likely secondary to the downregulation of Arc/Arg3.1 gene in striatal neurons. Evidence has already been provided that Arc/Arg3.1 gene is downregulated also in a lipopolysaccharide model of neuroinflammation (Bonow et al, 2008).…”

“…We focused our attention on the group of the immediate early genes, because they are rapidly regulated during stimulation (Lyford et al, 1995). Among them, Arc/Arg3.1 gene has been shown to be regulated in the brain by neuroinflammation (Bonow et al, 2008) and to be implicated in the regulation of the AMPA receptor subunit GluR1 and in AMPA receptor-mediated synaptic transmission. Accordingly, downregulation of Arc/Arg3.1 gene expression has been convincingly associated with increased AMPA receptormediated synaptic transmission Shepherd et al, 2006).…”

MPTP-Induced Neuroinflammation Increases the Expression of Pro-Inflammatory Cytokines and Their Receptors in Mouse Brain

“…However, the functional relevance of these data remains unclear. In this context, LPS has been reported to exacerbate neuroinflammation-based diseases [11,12] , by stimulating microglia to produce pro-inflammatory mediators such as cytokines, chemokines and reactive oxygen and nitrogen derivatives [13,14] . The presence of oxidative stress and inflammatory activity is one of the significant pathological features of PD [15] .…”

Interleukin-1β-induced memory reconsolidation impairment is mediated by a reduction in glutamate release and zif268 expression and α-melanocyte-stimulating hormone prevented these effects

“…This is an early transcription factor and is activated soon during memory reconsolidation (Tronson and Taylor, 2007). Also, it was reported that following a single intracerebroventricular injection of LPS into the lateral ventricle of mice, zif-268 expression was significantly lower in cortex, but not in hippocampus (Bonow et al, 2009). In this report mice were not trained in any behavioral protocol.…”