Nrf1 and Nrf2 Knockdown Effect in Anxiety-related Behavior and Mitochondrial Function

Introduction:  Nuclear factor, erythroid-derived 2, -like2 (Nrf2) and Nuclear erythroid 2-related factor 1 (Nrf1) stand as two important regulators of antioxidant defense system. Materials and Methods: Small interfering RNA (siRNA) targeting Nrf1 and Nrf2 (Nrf1&2) was injected in dorsal third ventricle of adult male albino Wistar rats. Anxiety-related behaviors and protein level of mitochondrial biogenesis, apoptotic marker factors and also electron transport chain (ETC), Citrate synthase (CS) and Malate dehydrogenase (MDH) enzymes activity in three brain regions: hippocampus, prefrontal cortex, and amygdala were evaluated. Results: Nrf1&2-silenced rats induced anxiety-like behaviors compared to the control group. The level of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1a) protein increased in those three regions. Although Nrf1&2-silencing decreased MDH activity in hippocampus and prefrontal cortex, the activity of CS was increased in all three mentioned areas. However, Nrf1&2 silencing had no effect in complex I and II-III activity, but complex IV activity was increased, particularly in amygdala. Furthermore, Bax/Bcl2 ratio and cleavage of caspase-3 was increased in all mentioned areas of the brain in Nrf1&2-silenced group. Conclusion: In conclusion, the presented data evaluated the complexity of mitochondrial functions and Nrf1 and Nrf2 in rat’s brain and points to mitochondrial crucial role in oxidative stress, energy metabolism, and behavior. &nbsp

Transgenerational influence of parental morphine exposure on pain perception, anxiety-like behavior and passive avoidance memory among male and female offspring of Wistar rats

Accumulating evidence suggests that epigenetic mechanisms play an important role in the formation and maintenance of memory within the brain. Moreover, the effect of parental drug-exposure before gestation on behavioral state of offspring has been little studied. The main objective of the current study is to evaluate the effect of parental morphine exposure on avoidance memory, morphine preference and anxiety-like behavior of offspring. The total of 32 males and 32 females were used for mating. The animals were treated with morphine. The offspring according to their parental morphine treatment was divided into four groups (n=16) including paternally treated, maternally treated, both of parents treated and naïve animals. The pain perception, anxiety-like behavior, and avoidance memory were evaluated in the offspring. In the current study, the total of 256 offspring was used for the experiments (4 tasks × 4 groups of offspring × 8 female offspring × 8 male offspring). The finding revealed that the avoidance memory and visceral pain were reduced significantly in male and female offspring with at least one morphine-treated parent. Moreover, anxiety-like behavior was reduced significantly in the male offspring with at least one morphine-treated parent. While anxiety-like behavior was increased significantly in female offspring that were treated by morphine either maternally or both of parents. The data revealed that the endogenous opioid system may be altered in the offspring of morphine-treated parent(s), and epigenetic role could be important. However, analysis of variance signified the important role of maternal inheritance

Tramadol Treatment Induces Change in Phospho-Cyclic Adenosine Monophosphate Response Element-Binding Protein and Delta and Mu Opioid Receptors within Hippocampus and Amygdala Areas of Rat Brain

Background: Tramadol induces its unique effects through opioid pathways, but the exact mechanism is not known. The study aims to evaluate changes in the level of mu-opioid receptor (μOR), delta-opioid receptor (δOR), and phosphorylated cyclic adenosine monophosphate (cAMP) response element-binding protein (p-CREB) in the hippocampus (HPC) and amygdala (AL) areas of tramadol-treated rats.Methods: For this purpose, a total of 36 male rats were divided into two main groups for chronic or acute tramadol exposure. The animals were then exposed to 5 mg.kg-1 of tramadol, 10 mg.kg-1 of tramadol, and normal saline. The HPC and AL areas of the animals were dissected upon completion of the period. The levels of p-CREB and μOR were quantified using the western blotting technique. The data were subjected to analysis of variance (ANOVA) followed by Tukey’s post-hoc analysis. The differences with the P-value lower than 0.05 were considered as significant.Findings: In the HPC and AL areas of the brain, the level of μOR was decreased by acute tramadol exposure, while no significant difference was observed by chronic tramadol exposure. Moreover, results showed that the level of p-CREB dose-dependently increased by acute and chronic tramadol exposure.Conclusion: HPC and AL are essential in the control of tramadol abuse. Tramadol abuse affects gene expression and transcription factors such as CREB. With acute drug tramadol treatments, the level of cAMP response element-binding protein (CREB) rapidly increases, while by chronic tramadol treatment, “peak and trough pattern is observing”. The activation of the rewarding mechanism is a precise instance of addictive behavior in tramadol-treated individuals

Correlation among the Behavioral Features in the Offspring of Morphine-Abstinent Rats

Background: Critical analysis of new evidence in medical sciences relies on statistics in terms of correlation.The aim of the present study was to evaluate the correlation coefficients among the behavioral features in theoffspring of morphine-abstinent parent(s).Methods: The offspring of various types of parental morphine-exposure were divided into 4 groups includingoffspring of healthy parents (CTL), offspring of paternal morphine-abstinence (PMA), offspring of maternalmorphine-abstinence (MMA), and offspring of both morphine-abstinence (BMA). Pain perception,depression-like behavior, and avoidance memory in the offspring were quantified. The logical structure ofassociation was measured using the Pearson correlation analysis.Findings: A strong correlation was observed between pain and depressive-like behavior in female and maleoffspring of healthy parents. Moreover, in the male and female offspring of healthy parents and BMA, nosignificant correlation was observed between avoidance memory and pain behavior or depressive-likebehavior. However, in the offspring of MMA, a strong correlation was observed between avoidance memoryand depressive-like behavior.Conclusion: The results of the study signified the importance of correlation analysis in addictive behavior. Theresults revealed that the pattern of correlation of the behavior of the offspring of MMA and PMA differe

Introduction to Neurocircuitry and Neurobiology of Anxiety

Context: Nowadays, experiencing occasional anxiety is a common part of each person’s life. The number of anxious people has increased in this modern life style. This study aimed to review some researches as to accelerate searching for new anxiolytic treatments. Evidence Acquisition: Related articles were extracted from databases including PubMed, Google Scholar, Springer, Science Direct and Wiley. Forty-eight articles were chosen. The articles were carefully considered, and after extracting information, they were categorized and integrated in the appropriate sequences to meet the needs of this study. Results: This review mentions the important brain regions involved in anxiety; it then continues with encapsulating some of the neurotransmitters’ and neuropeptides’ functions that cope with anxiety-like behaviors. Conclusion: With regard to the results, it is suggested that anxiety can be caused by change in the brains’ neurotransmitters level but more studies are needed to identify its exact mechanism

Expression of NMDA receptor subunits in human blood lymphocytes: A peripheral biomarker in online computer game addiction

Background and aims Repeated performance of some behaviors such as playing computer games could result in addiction. The NMDA receptor is critically involved in the development of behavioral and drug addictions. It has been claimed that the expression level of neurotransmitter receptors in the brain may be reflected in peripheral blood lymphocytes (PBLs). Methods Here, using a real-time PCR method, we have investigated the mRNA expression of GluN2A, GluN2D, GluN3A, and GluN3B subunits of the NMDA receptor in PBLs of male online computer game addicts (n = 25) in comparison with normal subjects (n = 26). Results Expression levels of GluN2A, GluN2D, and GluN3B subunits were not statistically different between game addicts and the control group. However, the mRNA expression of the GluN3A subunit was downregulated in PBLs of game addicts. Discussion and conclusions Transcriptional levels of GluN2A and GluN2D subunits in online computer game addicts are similar to our previously reported data of opioid addiction and are not different from the control group. However, unlike our earlier finding of drug addiction, the mRNA expression levels of GluN3A and GluN3B subunits in PBLs of game addicts are reduced and unchanged, respectively, compared with control subjects. It seems that the downregulated state of the GluN3A subunit of NMDA receptor in online computer game addicts is a finding that deserves more studies in the future to see whether it can serve as a peripheral biomarker in addiction studies, where the researcher wants to rule out the confusing effects of abused drugs

Measurement of the top quark forward-backward production asymmetry and the anomalous chromoelectric and chromomagnetic moments in pp collisions at √s = 13 TeV

Abstract The parton-level top quark (t) forward-backward asymmetry and the anomalous chromoelectric (d̂ t) and chromomagnetic (μ̂ t) moments have been measured using LHC pp collisions at a center-of-mass energy of 13 TeV, collected in the CMS detector in a data sample corresponding to an integrated luminosity of 35.9 fb−1. The linearized variable AFB(1) is used to approximate the asymmetry. Candidate t t ¯ events decaying to a muon or electron and jets in final states with low and high Lorentz boosts are selected and reconstructed using a fit of the kinematic distributions of the decay products to those expected for t t ¯ final states. The values found for the parameters are AFB(1)=0.048−0.087+0.095(stat)−0.029+0.020(syst),μ̂t=−0.024−0.009+0.013(stat)−0.011+0.016(syst), and a limit is placed on the magnitude of | d̂ t| < 0.03 at 95% confidence level. [Figure not available: see fulltext.

MUSiC : a model-unspecific search for new physics in proton-proton collisions at root s=13TeV

Results of the Model Unspecific Search in CMS (MUSiC), using proton-proton collision data recorded at the LHC at a centre-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 35.9 fb(-1), are presented. The MUSiC analysis searches for anomalies that could be signatures of physics beyond the standard model. The analysis is based on the comparison of observed data with the standard model prediction, as determined from simulation, in several hundred final states and multiple kinematic distributions. Events containing at least one electron or muon are classified based on their final state topology, and an automated search algorithm surveys the observed data for deviations from the prediction. The sensitivity of the search is validated using multiple methods. No significant deviations from the predictions have been observed. For a wide range of final state topologies, agreement is found between the data and the standard model simulation. This analysis complements dedicated search analyses by significantly expanding the range of final states covered using a model independent approach with the largest data set to date to probe phase space regions beyond the reach of previous general searches.Peer reviewe

Measurement of prompt open-charm production cross sections in proton-proton collisions at root s=13 TeV

The production cross sections for prompt open-charm mesons in proton-proton collisions at a center-of-mass energy of 13TeV are reported. The measurement is performed using a data sample collected by the CMS experiment corresponding to an integrated luminosity of 29 nb(-1). The differential production cross sections of the D*(+/-), D-+/-, and D-0 ((D) over bar (0)) mesons are presented in ranges of transverse momentum and pseudorapidity 4 < p(T) < 100 GeV and vertical bar eta vertical bar < 2.1, respectively. The results are compared to several theoretical calculations and to previous measurements.Peer reviewe

Measurement of b jet shapes in proton-proton collisions at root s=5.02 TeV

We present the first study of charged-hadron production associated with jets originating from b quarks in proton-proton collisions at a center-of-mass energy of 5.02 TeV. The data sample used in this study was collected with the CMS detector at the CERN LHC and corresponds to an integrated luminosity of 27.4 pb(-1). To characterize the jet substructure, the differential jet shapes, defined as the normalized transverse momentum distribution of charged hadrons as a function of angular distance from the jet axis, are measured for b jets. In addition to the jet shapes, the per-jet yields of charged particles associated with b jets are also quantified, again as a function of the angular distance with respect to the jet axis. Extracted jet shape and particle yield distributions for b jets are compared with results for inclusive jets, as well as with the predictions from the pythia and herwig++ event generators.Peer reviewe