The effects of (+)8-OH-DPAT (16 μg) and of both active doses of NLX-101 (0.25 and 16 μg) were prevented by the 5-HT1A receptor antagonist WAY-100,635 (0.63 mg/kg s.c.). In conclusion, activation of 5-HT1A receptors in the PFC by NLX-101 produces robust antidepressant-like effects in the rat FST, with a distinctive bimodal dose-response pattern. These data suggest that NLX-101 may target specific 5-HT1A receptor subpopulations in PFC, likely located on GABAergic and/or glutamatergic neurons.Substance use disorders are a debilitating neuropsychiatric condition, however it remains unclear why some individuals are at greater risk of substance use disorders than others and what genetic factors determine such individual differences. Impulsivity appears a promising candidate endophenotype to bridge the gap between genetic risk and addiction. Brain-derived neurotrophic factor (BDNF), and in particular the BDNFVal66Met polymorphism, has been suggested to be involved in both impulsivity and substance use disorders, however results so far have been inconsistent. To investigate the role of BDNF, and more specifically the BDNFVal66Met polymorphism, in both impulsivity and operant alcohol self-administration using the same animal model. Separate cohorts of humanized Val66Met transgenic mice were assessed for either trait impulsivity in the 5-choice serial reaction time (5-CSRT) touchscreen task, or propensity towards obtaining ethanol in an operant paradigm. It was found that female hBDNFVal/Val mice exhibited both greater impulsivity compared to hBDNFMet/Met mice of the same sex as shown by a higher number of premature responses at one of three increased inter-trial intervals tested in the 5-CSRT task, and a greater propensity toward stable ethanol self-administration relative to male mice of the same genotype in the operant paradigm. By contrast, male mice showed no difference between genotypes in impulsivity or stable ethanol self-administration. The hBDNFMet/Met genotype appears to sex-specifically alter aspects of both impulsive behaviour and addiction propensity. bpV These results suggest that impulse behaviour may be a possible predictor of addiction risk.Rehabilitation training is routine for children who experience stroke, but its protective mechanism remains unclear. To study the effect of treadmill training intensity on hippocampal synaptic plasticity after cerebral ischemia, a model of middle cerebral artery occlusion (MCAO)/reperfusion was established in young rats to simulate childhood ischemic stroke. The rats were randomly allocated into five groups sham operation, MCAO, low-intensity exercise and MCAO (5 m/min), medium-intensity exercise and MCAO (10 m/min), and high-intensity exercise and MCAO (15 m/min). Intervention was continued for 14 days, and a series of experimental tests were conducted. After MCAO, the juvenile rats exhibited a series of morphological and functional alterations, including changes in their neurobehavior and cerebral infarct volumes. Compared with control rats, MCAO rats had a longer escape latency and crossed fewer platforms in the water maze test and exhibited decreased hippocampal neuron density and Synapsin I and PSD95 exprticosterone, with the high-intensity training having the most obvious effect. Treadmill training can provide neuroprotection by promoting hippocampal synaptic plasticity, with medium-intensity training showing the most optimal effects.Automated touchscreen techniques find increasing application for the assessment of cognitive function in rodents. However, hardly anything is known about the potential impact of touchscreen-based training and testing procedures on the animals under investigation. Addressing this question appears particularly important in light of the long and intensive training phases required for most of the operant tasks. Against this background, we here investigated the influence of regular touchscreen training on hormones and behaviour of mice. Faecal corticosterone metabolites (FCMs), reflecting corticosterone levels around the time of treatment, were significantly increased in touchscreen-trained mice, even one week after the training phase was already terminated. Such an effect was not detected on baseline FCMs. Thus, regular touchscreen training can be assumed to cause long-term effects on hypothalamus-pituitary-adrenal axis activity. Furthermore, anxiety-like behaviour was increased in touchscreen-trained mice two weeks after the end of the training phase. Traditionally, this would be interpreted as a negative influence of the training procedure on the animals’ affective state. Yet, we also provide two alternative explanations, taking the possibility into account that touchscreen training might have enriching properties.

Helicobacter pylori (Hp) infection plays an important role in the development of gastric cancer. Hp can secrete gamma-glutamyltransferase (GGT), however, the impact of GGT of Hp on the human gastric cells is not clear. Although it has been demonstrated that ten-eleven translocation 1 (TET1) is overexpressed in gastric cancer, the relationship between the GGT of Hp and TET1 has not been studied. The aim of this study was to explore the relationship between GGT and TET1, and the role of TET1 in the development of gastric cancer induced by Hp was also explored.

The correlation between TET1 and prognosis of gastric adenoma cancer was analyzed by bioinformatics. The GGT gene of Hp26695 was knocked out by electroporation with plasmid to construct the GGT knockout strain of Hp (Hp-KS-1). The shTET1 lentivirus transfected GES-1, MGC-803 and SGC-7901 cell lines were constructed. The biological characteristics of the three kind of cells were detected.

TET1 was overexpressed in gastric tissues of Hp infected patients and mice. Bioinformatics analysis showed that in patients with gastric cancer, higher TET1 expression would result in poorer prognosis. The GGT gene of Hp can lead to overexpression of TET1 in GES-1, MGC-803 and SGC-7901 cells, along with the activation of Wnt/β-catenin signaling pathway, and then promoting tumorigenesis. After silencing TET1, the Wnt/β-catenin signaling pathway which was activated by GGT of Hp was inhibited.

GGT of Helicobacter pylori can promote gastric carcinogenesis by activating Wnt/β-catenin signaling pathway trough up-regulating TET1.

GGT of Helicobacter pylori can promote gastric carcinogenesis by activating Wnt/β-catenin signaling pathway trough up-regulating TET1.