Search

OLIG2 is a transcription factor that activates the expression of myelin-associated genes in the oligodendrocyte-lineage cells. However, the mechanisms of myelin gene inactivation are unclear. Here, we uncover a non-canonical function of OLIG2 in transcriptional repression to modulate myelinogenesis by functionally interacting with tri-methyltransferase SETDB1. Immunoprecipitation and chromatin-immunoprecipitation assays show that OLIG2 recruits SETDB1 for H3K9me3 modification on the Sox11 gene, which leads to the inhibition of Sox11 expression during the differentiation of oligodendrocytes progenitor cells (OPCs) into immature oligodendrocytes (iOLs). Tissue-specific depletion of Setdb1 in mice results in the hypomyelination during development and remyelination defects in the injured rodents. Knockdown of Sox11 by siRNA in rat primary OPCs or depletion of Sox11 in the oligodendrocyte lineage in mice could rescue the hypomyelination phenotype caused by the loss of OLIG2. In summary, our work demonstrates that the OLIG2-SETDB1 complex can mediate transcriptional repression in OPCs, affecting myelination. Transcription factors regulate gene programs during myelination. Here, the authors show that the Oligodendrocyte Transcription Factor 2 (OLIG2) regulates the differentiation of oligodendrocyte progenitor cells into immature oligodendrocytes via SETDB1 during myelination and remyelination in rodents. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to compare the effects of colonic electrical stimulation (CES) on gastrointestinal transit time (GITT), energy consumption, stool frequency, stool consistency, and food intake using different individual parameter patterns and stimulation sites. Methods: Eight beagle dogs underwent surgery and CES. First, CES was conducted to determine the individual parameters with different pulse configurations, based on symptoms. Second, influences on energy consumption and GITT were compared between CES sessions with different pulse configurations. Third, GITT, stool frequency, stool consistency, and food intake were compared to assess the effects of CES at different stimulation sites. Results: The individual parameters varied greatly among the dogs. In proximal colon electrical stimulation (PCES) and rectosigmoid colon electrical stimulation (RCES), energy consumption was lower with the constant pulse width mode than with the constant pulse amplitude mode ( p = 0.012 and p = 0.018, respectively). There was no statistical difference between the two pulse configurations in GITT assessment. The PCES, RCES, and sequential CES sessions significantly accelerated GITT compared to sham stimulation. There was no statistical difference in GITT between PCES, RCES, and sequential CES sessions. Compared to sham CES session, RCES and sequential CES sessions exhibited significant higher stool frequency ( p < 0.001 and p = 0.001, respectively), and PCES and RCES sessions inhibited food intake ( p = 0.003 and p = 0.002, respectively). Conclusions: Constant pulse width mode is an appropriate pulse configuration for individual CES. At different stimulation sites, CES may exert different effects on stool frequency and food intake. This study provides an experimental basis for the clinical application of CES. [ABSTRACT FROM AUTHOR]

The original version of this Article contained an error in the "Animals" section of the Methods, which incorrectly read ' I Cnp-Cre, Olig2 i SP I Flox/Fox i sp and I Sox11 i SP I Flox/Flox i sp mice were generously provided by Dr. Luis F. Parada (Department of Developmental Biology, University of Texas Southwestern Medical School, Dallas, TX, USA)'. The correct version adds 'Cnp-Cre (generated by Dr. Klaus Nave), I Olig2 i SP I Flox/Fox i sp and I Sox11 i SP I Flox/Flox i sp mice were generously provided by Dr. Luis F. Parada (Department of Developmental Biology, University of Texas Southwestern Medical School, Dallas, TX, USA)'. [Extracted from the article]

Background: To improve the therapeutic effects of gastric electrical stimulation (GES) for obesity, an animal experiment was conducted using a new type of stimulators. Proper parameters of GES were selected, and the impacts of GES on the food intake and gastric accommodation of canines were observed. Methods: Eight beagle dogs were operated on, and GES was performed on them. Firstly, GES was performed to determine the right parameters according to symptoms. Secondly, the so selected parameters were used in a 3-day GES procedure, during which process food intake, body weight, and symptoms were recorded. Thirdly, the gastric capacities before and after GES with different pulse widths were measured by means of a barostat. Results: The selected parameters varied for each dog, with the pulse widths ranging from 0.3 to 6 ms. The food consumption after GES dropped significantly as compared with the amount observed in the sham stimulation. Tolerance to stimulation could be observed during GES. The post-GES gastric fundus capacity increased evidently in comparison with the capacity before GES, suggesting significant distention as compared with sham stimulation. Given an increment of 2 ms in the pulse width twice, the gastric capacity continued to distend each time. Conclusions: GES featuring pulse trains with wider and individualized pulse widths could inhibit food consumption of dogs. The stimulation parameters should be selected individually and adjusted periodically. GES of this mode could also increase the fasting gastric capacity with certain dose-related effects. The new type of stimulators may be more suitable for the treatment of human obesity than traditional stimulators. [ABSTRACT FROM AUTHOR]

Background: Gastric electrical stimulation (GES) has been proposed as a promising therapeutic option in treating obesity for 20 years. Currently, the available device of GES cannot meet the clinical needs. The purpose of this study is to verify the effect of a new type of adjustable gastric electrical stimulator in reducing food intake and body weight. Methods: Eight beagle dogs randomly followed GES and sham GES for 3 months in a crossover design. Parameters were adjusted and individualized during the experiment. Symptoms of GES were recorded, and the effective parameters were selected. Resistance to GES was assessed. Food intake and body weight were measured to evaluate the effect of GES. Results: The effective parameters were varied among the dogs. Resistance to GES was observed in different periods in dogs. Parameters needed to be adjusted every 10.2 ± 2.1 days during the period of GES. Food intake during GES for 3 months was significantly reduced than that during sham GES of 3 months ( P < 0.05). With the decreased food intake, body weight was significantly reduced by the end of GES of 3 months compared with that of sham GES of 3 months ( P < 0.05). Conclusions: Food intake and body weight of dogs are significantly reduced by adjustable GES. Individual parameters and resistance during GES are required to be considered. The new adjustable device may have good prospects of clinical application for obesity. [ABSTRACT FROM AUTHOR]