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

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 post­intraperitoneal injection of LPS, mouse brain tissues, including tissues from the cortex, striatum, hippocampus and hypothalamus, were collected. Reverse transcription­polymerase 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.

Neurohypophyseal Neuregulin 1 Is Derived from the Hypothalamus as a Potential Prolactin Modulator.

Although neuregulin 1 (Nrg1) has been identified in the rat hypothalamus, the localisation of Nrg1 in the hypothalamus-hypophyseal structure and its functions remain unclear and require further elucidation. In this study, we identified the existence of Nrg1ß types I-III in the rat hypothalamus. We demonstrated that Nrg1 was partially localised in somatostatin-positive cells in the periventricular nucleus. It was also co-localised with arginine vasopressin in the supraoptic nucleus, median eminence and pituitary stalk. Nrg1 was also extensively distributed in the posterior pituitary (PP), including the projected neuronal fibres that surround the vascular structure and Herring bodies. Western blotting confirmed that these signals were primarily produced by soluble Nrg1 derived from a 45-kDa Nrg1 precursor mainly identified in the hypothalamus. Similar to Nrg1α, Nrg1ß increased the prolactin (PRL) expression in rat pituitary RC-4B/C cells, which can be inhibited by an Akt inhibitor. In addition, Nrg1ß had no apparent effect on growth hormone expression at the mRNA or protein levels. Collectively, we conclude that hypothalamic Nrg1 may be transported to the PP as the ß form. We further hypothesise that Nrg1ß may function via the regulation of PRL expression through a paracrine mechanism.

Quercetin promotes cell apoptosis and inhibits the expression of MMP-9 and fibronectin via the AKT and ERK signalling pathways in human glioma cells.

Gliomas are the most common and malignant primary brain tumours and are associated with a poor prognosis despite the availability of multiple therapeutic options. Quercetin, a traditional Chinese medicinal herb, is an important flavonoid and has anti-cancer activity. Here, we evaluated whether quercetin could inhibit glioma cell viability and migration and promote apoptosis. The treatment of U87-MG glioblastoma and U251 and SHG44 glioma cell lines with different concentrations of quercetin inhibited cell viability in a dose-dependent manner. Wound healing assays indicated that quercetin significantly decreased glioma cell migration. ß-galactosidase staining, DNA staining and Annexin V-EGF/PI double staining assays demonstrated that quercetin promoted cell senescence and apoptosis. In addition, the protein levels of p-AKT, p-ERK, Bcl-2, matrix metallopeptidase 9 (MMP-9) and fibronectin (FN) were significantly reduced following quercetin treatment. Therefore, we conclude that quercetin might inhibit the viability and migration and promote the senescence and apoptosis of glioma cells by suppressing the Ras/MAPK/ERK and PI3K/AKT signalling pathways. Quercetin might be a potential candidate for the clinical treatment of glioma.