Bairdhede9245
We focus on the importance of signalling initiated by the release of BDNF and a prime downstream effector, MSK1, in orchestrating the many structural and functional neuronal adaptations associated with enrichment. In particular we discuss the MSK1-dependent expansion of the dynamic range of the glutamatergic synapse, which may allow enhanced information storage or processing, and the establishment of a genomic homeostasis that may both stabilise the enriched brain, and may make it better able to respond to novel experiences.Alcohol consumption is mediated by several important neuromodulatory systems, including the endocannabinoid and neuropeptide Y (NPY) systems in the limbic brain circuitry. However, molecular mechanisms through which cannabinoid-1 (CB1) receptors regulate alcohol consumption are still unclear. Here, we investigated the role of the CB1 receptor-mediated downstream regulation of NPY via epigenetic mechanisms in the amygdala. Alcohol drinking behavior was measured in adult male C57BL/6J mice treated with a CB1 receptor neutral antagonist AM4113 using a two-bottle choice paradigm while anxiety-like behavior was assessed in the light-dark box (LDB) test. The CB1 receptor-mediated changes in the protein levels of phosphorylated cAMP-responsive element binding protein (pCREB), CREB binding protein (CBP), H3K9ac, H3K14ac and NPY, and the mRNA levels of Creb1, Cbp, and Npy were measured in amygdaloid brain structures. N6F11 cell line Npy-specific changes in the levels of acetylated histone (H3K9/14ac) and CBP in the amygdala were also measured. We found that the pharmacological blockade of CB1 receptors with AM4113 reduced alcohol consumption and, in an ethanol-naïve cohort, reduced anxiety-like behavior in the LDB test. Treatment with AM4113 also increased the mRNA levels of Creb1 and Cbp in the amygdala as well as the protein levels of pCREB, CBP, H3K9ac and H3K14ac in the central and medial nucleus of amygdala, but not in the basolateral amygdala. Additionally, AM4113 treatment increased occupancy of CBP and H3K9/14ac at the Npy gene promoter, leading to an increase in both mRNA and protein levels of NPY in the amygdala. These novel findings suggest that CB1 receptor-mediated CREB signaling plays an important role in the modulation of NPY function through an epigenetic mechanism and further support the potential use of CB1 receptor neutral antagonists for the treatment of alcohol use disorder.The role of glucose transporters (GLUTs) in diabetes mellitus has become more prominent as a possible therapeutic target. In the present study, we aimed to compare the effect of zinc oxide nanoparticles (ZnONPs), silver nanoparticles (AgNPs), and docosahexaenoic acid (DHA) alone or loaded in ZnONPs or AgNPs on insulin signaling pathway and GLUTs expression in diabetic rats. In the experimental part, rats were divided into seven groups; control, diabetic, and the other five groups were diabetic received different treatments. Fasting blood sugar (FBS), serum level of insulin, insulin resistance (IR), and serum level of phosphatidylinositol 3-kinase (PI3K) were evaluated. In addition, insulin expression in pancreatic islets was assessed by immunohistochemical analysis, and the expression of liver GLUTs 1, 2, and 4 and liver insulin receptor substrate-1 (IRS-1) was evaluated by real-time polymerase chain reactions (RT-PCR). The results of the current study showed that ZnONPs, AgNPs, and DHA alone or loaded in ZnONPs or AgNPs attenuated levels of FBS, insulin and decreased IR in diabetic rats through enhancing the expression of GLUTs as well as IRS-1 and PI3K. Furthermore, AgNPs loaded with DHA showed the most significance with high comparability to the control group. In conclusion, this study elucidated the role of GLUTs and IRS-1 in diabetes and introduced novel characteristics of ZnONPs, AgNPs, and DHA alone or loaded in ZnONPs or AgNPs as a therapeutic modality to activate GLUTs and IRS1, which may be beneficial for diabetic patients with IR.Although previous studies have documented that relational victimization serves as a risk factor for depressive symptoms across developmental periods, heterogeneity in effects highlights the possibility that some individuals may be especially vulnerable. This study examined two factors that may influence the link between relational victimization and depressive symptoms physiological reactivity and narrative processing during the recounting of a past victimization experience. In a sample of 200 college students, we examined narrative processing (i.e., use of disengagement coping strategies, positive resolution, and primary control coping strategies) and respiratory sinus arrhythmia (RSA) reactivity, assessed during a standard laboratory interview, as moderators of the link between self-reported relational victimization and depressive symptoms. Although relational victimization was associated with increased rates of depressive symptoms, a combination of RSA activation and high disengagement coping appeared protective for individuals high in relational victimization. Similarly, a combination of RSA activation and high levels of positive resolution appeared protective against depressive symptoms among individuals high in relational victimization. The findings shed critical light on the interaction of physiological and cognitive processes in coping with relational victimization.Working memory (WM) can be considered as a limited-capacity system which is capable of saving information temporarily with the aim of processing. The aim of the present study was to establish whether eccentricity representation in WM could be decoded from eletroencephalography (EEG) alpha-band oscillation in parietal cortex during delay-period while performing memory-guided saccade (MGS) task. In this regard, we recorded EEG and Eye-tracking signals of 17 healthy volunteers in a variant version of MGS task. We designed the modified version of MGS task for the first time to investigate the effect of locating stimuli in two different positions, in a near (6°) eccentricity and far (12°) eccentricity on saccade error as a behavioral parameter. Another goal of study was to discern whether or not varying the stimuli loci can alter behavioral and eletroencephalographical data while performing the variant version of MGS task. Our findings demonstrate that saccade error for the near fixation condition is significantly smaller than the far from fixation condition.