فریده طالبی

The footprint of Neuregulin 1 (NRG1) / ERbB4 in the pathophysiology of some neurological disorders and TRPV1 regulation has been indicated. The alterations in NRG1 and ErbB4 as well as the TRPV1 signaling pathway were investigated during the development of absence epilepsy in the genetic animal model of absence epilepsy.

Male WAG/Rij and Wistar rats were divided into four experimental groups of two and six months of age. The protein levels of NRG1, ERbB4, and TRPV1 were measured in the somatosensory cortex and hippocampus. 

The cortical protein levels of NRG1 and ErbB4 in the 6-month-old WAG/Rij rats were lower than in Wistar rats. Protein levels of TRPV1 were lower in two- and six-month-old WAG/Rij rats compared to age-matched Wistar rats.Hippocampal protein levels of NRG1 in 6-month-old WAG/Rij rats were lower than two-month-old WAG/Rij rats. Low levels of ErbB4 protein in two-month-old and high levels in six-month-old WAG/Rij rats were found compared to Wistar rats. Protein levels of TRPV1 were lower in the two-month-old and higher in the six-month-old WAG/Rij rats compared to age-matched Wistar rats. Furthermore, a high correlation between NRG1/ERbB4 and TRPV1 expressions in the cortex and hippocampus was indicated. The expression of NRG1/ERbB4 and TRPV1 followed a similar pattern during the life span of Wistar and WAG/Rij rats.

Our findings indicated the potential role of the NRG1/ErbB4 pathway as well as TRPV1 in the pathogenesis of absence epilepsy. The regulatory effect of the ERbB4 receptor on the TRPV1 expression has been suggested following the similar pattern of expression.

Sulfur mustard as a chemical warfare agent causes short and long-term pulmonary complications in its victims. MicroRNAs are known to act as remarkable regulators of biological pathways, monitoring, and treatment of diseases including respiratory problems. In this study, we investigated the expression of miR-106a-5p and miR-106b-5p, two regulators of TGF-β signaling, as well as their target molecule, TGFβ1I1, in peripheral blood mononuclear cells from SM-exposed individuals. A total of 70 veterans with SM-induced pulmonary complications were examined and compared to 35 gender and age-matched healthy controls. After clinical examination and pulmonary function tests, the severity of pulmonary complications was classified. Total RNA was extracted from PBMCs and the purity of extracted RNA samples was evaluated by a NanoDrop 2000. The miR-106a-5p, miR-106b-5p, and TGFβ1I1 expression levels were measured by real-time RT-PCR. The miR-106a-5p expression levels were significantly increased in both mild (P=0.015) and severe groups compared with the control group. The miR-106b-5p expression levels were considerably elevated in the severe group TGFβ1I1 expression levels were notably reduced in the severe group compared with the control group. Although, a slight decrease in TGFβ1I1 expression levels was observed in the mild group compared with the control. Our results indicate that exposure to sulfur mustard affects the expression of miR-106a-5p, miR-106b-5p, and their target gene, TGFβ1I1, in peripheral blood mononuclear cells. Considering the role of TGFβ1I1 in the regulation of TGF-β signaling, the mentioned changes might point to a potential mechanism by which SM exposure causes chronic pulmonary complications. In a ROC analysis, miR-106a-5p and miR-106b-5p potentially turned out to be a suitable diagnostic biomarker in the mild and severe categories of patients. Although, miR-106a-5p could be considered a better biomarker than miR-106b-5p.

MicroRNAs are small non-coding RNAs that regulate gene expression and involve in many cellular and physiological mechanisms. Recent studies have revealed that dysregulation of microRNAs might contribute to autoimmune disorders such as Multiple Sclerosis (MS). Based on these findings, we examined the potential role of miR-320 isoforms; miR-320-3p and miR-320-5p, in the context of autoimmune neuroinflammation and pathogenesis of EAE, which is an animal model of MS. The expression levels of miR-320-3p and miR-320-5p, and their predicted target genes, TGFBR2 and Smad2, were quantified in the CNS tissue in mice with Experimental Autoimmune Encephalomyelitis (EAE) using RT-PCR method. The expression was also examined in splenocytes macrophages and astrocytes. To examine the interaction of miR-320-3p and miR-320-5p with the 3′-UTR of potential target transcripts, the mimic sequences of both isoforms were transfected into splenocytes and then examined by RT-PCR. The expression of both isoforms of miR-320 significantly increased in different phases of EAE and activated lymphocytes, whereas the levels of their predicted target genes, Smad2 and TGFBR2 decreased in these cells. Obtained data revealed that miR-320-5p level significantly increased in activated macrophages and astrocytes; however, the miR 320-3p level did not show significant changes in these cells after Lipopolysaccharide (LPS) stimulation. The levels of TGFBR2 and Smad2 decreased in transfected splenocytes. Our findings suggest that upregulation of miR-320 isoforms might be involved in the neuroinflammation and pathogenesis of MS through targeting and suppression of TGFBR2 and Smad2, i.e. protective genes in MS.