ABSTRACT
Genetic animal models of epilepsy are an important tool for further understanding the basic cellular mechanisms underlying epileptogenesis and for developing novel antiepileptic drugs. We conducted a comparative study of gene expression in the inferior colliculus, a nucleus that triggers audiogenic seizures, using two animal models, the Wistar audiogenic rat (WAR) and the genetic audiogenic seizure hamster (GASH:Sal). For this purpose, both models were exposed to high intensity auditory stimulation, and 60min later, the inferior colliculi were collected. As controls, intact Wistar rats and Syrian hamsters were subjected to stimulation and tissue preparation protocols identical to those performed on the experimental animals. Ribonucleic acid was isolated, and microarray analysis comparing the stimulated Wistar and WAR rats showed that the genomic profile of these animals displayed significant (fold change, |FC|≥2.0 and p<0.05) upregulation of 38 genes and downregulation of 47 genes. Comparison of gene expression profiles between stimulated control hamsters and stimulated GASH:Sal revealed the upregulation of 10 genes and the downregulation of 5 genes. Among the common genes that were altered in both models, we identified the zinc finger immediate-early growth response gene Egr3. The Egr3 protein is a transcription factor that is induced by distinct stress-elicited factors. Based on immunohistochemistry, this protein was expressed in the cochlear nucleus complex, the inferior colliculus, and the hippocampus of both animal models as well as in lymphoma tumors of the GASH:Sal. Our results support that the overexpression of the Egr3 gene in both models might contribute to neuronal viability and development of lymphoma in response to stress associated with audiogenic seizures. This article is part of a Special Issue entitled "Genetic and Reflex Epilepsies, Audiogenic Seizures and Strains: From Experimental Models to the Clinic".
Subject(s)
Acoustic Stimulation/adverse effects , Early Growth Response Protein 1/genetics , Early Growth Response Protein 2/genetics , Early Growth Response Protein 3/genetics , Epilepsy, Reflex/genetics , Seizures/genetics , Animals , Cricetinae , Early Growth Response Protein 1/biosynthesis , Early Growth Response Protein 2/biosynthesis , Early Growth Response Protein 3/biosynthesis , Epilepsy, Reflex/drug therapy , Epilepsy, Reflex/metabolism , Gene Expression , Genes, Immediate-Early/genetics , Genetic Predisposition to Disease/genetics , Hippocampus/metabolism , Male , Mesocricetus , Rats , Rats, Wistar , Rodentia , Seizures/drug therapy , Seizures/metabolism , Species SpecificityABSTRACT
Obesity and its complications are a major global health problem. In this study, we investigated the anti-obesity effect and mechanism of an edible plant, Bidens pilosa, and its active constituent. We first assessed the long-term effect of B. pilosa on body composition, body weight, blood parameters in ICR mice. We observed that it significantly decreased fat content and increased protein content in ICR mice. Next, we verified the anti-obesity effect of B. pilosa in ob/ob mice. It effectively and dose-dependently reduced fat content, adipocyte size and/or body weight in mice. Moreover, mechanistic studies showed that B. pilosa inhibited the expression of peroxisome proliferator activated receptor γ (PPARγ), CCAAT/enhancer binding proteins (C/EBPs) and Egr2 in adipose tissue. Finally, we examined the effect of 2-ß-D-glucopyranosyloxy-1-hydroxytrideca-5,7,9,11-tetrayne (GHT) on adipogenesis in adipocytes. We found that B. pilosa significantly decreased the adipogenesis and lipid accumulation. This decrease was associated with the down-regulation of expression of Egr2, C/EBPs, PPARγ, adipocyte Protein 2 (aP2) and adiponectin. In summary, this work demonstrated that B. pilosa and GHT suppressed adipogenesis and lipid content in adipocytes and/or animals via the down-regulation of the Egr2, C/EBPs and PPARγ pathways, suggesting a novel application of B. pilosa and GHT against obesity.
Subject(s)
Adipogenesis/drug effects , Bidens/chemistry , CCAAT-Enhancer-Binding Proteins/metabolism , Down-Regulation/drug effects , Lipid Metabolism/drug effects , PPAR gamma/metabolism , Plant Extracts/pharmacology , 3T3-L1 Cells , Adipose Tissue/metabolism , Adipose Tissue/pathology , Animals , Bidens/metabolism , CCAAT-Enhancer-Binding Proteins/genetics , Early Growth Response Protein 2/genetics , Early Growth Response Protein 2/metabolism , Female , Male , Mice , Mice, Inbred C57BL , Mice, Inbred ICR , Mice, Obese , PPAR gamma/genetics , Plant Extracts/chemistry , RNA, Messenger/metabolism , Rosiglitazone , Signal Transduction/drug effects , Thiazolidinediones/pharmacologyABSTRACT
Fast axonal conduction depends on myelin, which is formed by Schwann cells in the PNS. We found that the transcription factor Yin Yang 1 (YY1) is crucial for peripheral myelination. Conditional ablation of Yy1 in the Schwann cell lineage resulted in severe hypomyelination, which occurred independently of altered Schwann cell proliferation or apoptosis. In Yy1 mutant mice, Schwann cells established a 1:1 relationship with axons but were unable to myelinate them. The Schwann cells expressed low levels of myelin proteins and of Egr2 (also called Krox20), which is an important regulator of peripheral myelination. In vitro, Schwann cells that lacked Yy1 did not upregulate Egr2 in response to neuregulin1 and did not express myelin protein zero. This phenotype was rescued by overexpression of Egr2. In addition, neuregulin-induced phosphorylation of YY1 was required for transcriptional activation of Egr2. Thus, YY1 emerges as an important activator of peripheral myelination that links neuregulin signaling with Egr2 expression.