Differential changes in Neuregulin-1 signaling in major brain regions in a lipopolysaccharide-induced neuroinflammation mouse model

Abstract

Neuregulin 1 (Nrg1) is involved in multiple biological processes in the nervous system. The present study investigated changes in Nrg1 signaling in the major brain regions of mice subjected to lipopolysaccharide (LPS)-induced neuroinflammation. At 24 h post-intraperitoneal injection of LPS, mouse brain tissues, including tissues from the cortex, striatum, hippocampus and hypothalamus, were collected. Reverse transcription-polymerase chain reaction was used to determine the expression of Nrg1 and its receptors, Neu and ErbB4, at the mRNA level. Western blotting was performed to determine the levels of these proteins and the protein levels of phosphorylated extracellular signal-regulated kinases (Erk)1/2 and Akt1. Immunohistochemical staining was utilized to detect the levels of pNeu and pErbB4 in these regions. LPS successfully induced sites of neuroinflammation in these regions, in which changes in Nrg1, Neu and ErbB4 at the mRNA and protein levels were identified compared with controls. LPS induced a reduction in pNeu and pErbB4 in the striatum and hypothalamus, although marginally increased pErbB4 levels were found in the hippocampus. LPS increased the overall phosphorylation of Src but this effect was reduced in the hypothalamus. Moreover, increased phosphorylation of Akt1 was found in the striatum and hippocampus. These data suggest diverse roles for Nrg1 signaling in these regions during the process of neuroinflammation.

Dihydrolipoic acid protects against lipopolysaccharide-induced behavioral deficits and neuroinflammation via regulation of Nrf2/HO-1/NLRP3 signaling in rat

“…Previous studies have shown that LPS can significantly increase phosphorylation levels of ERK in the hippocampus of mice [41,42]. At the same time, one study demonstrated that LPS did not affect ERK phosphorylation in the hippocampus of mice [43]. In our study, we observed that LPS did not affect the phosphorylation of ERK in the hippocampus.…”

E6020, a synthetic TLR4 agonist, accelerates myelin debris clearance, Schwann cell infiltration, and remyelination in the rat spinal cord

“…Neuregulin 1 is a key regulator of Schwann cell migration, proliferation, and survival (Heermann & Schwab, ). Recently, systemic TLR4 activation was shown to alter neuregulin 1 expression in the brain (Yang et al, ), thus it is possible that TLR4 activation in the CNS can influence Schwann cell recruitment via neuregulin signaling. Our recent data implicate TLR4 signaling in regulating growth factor and cytokine expression in the damaged spinal cord (Church et al, ), therefore it is likely that E6020 treatment altered the inflammatory environment after lysolecithin demyelination to favor Schwann cell recruitment and survival.…”

Identification of novel biomarkers for prediction of neurological prognosis following cardiac arrest

“…They demonstrated different changes on Akt1 signaling in major mouse brain regions in response to LPS. The Akt1 level was significantly increased in the striatum, no changes in the cortex and hypothalamus, and an increase in hippocampus although no significant difference was found compared with the control mice [39]. Since most of cerebral I/R animal model studies were performed in the brain tissue, especially in the hippocampus, further studies looking at the level of Akt in blood are needed.…”