VGLUT1 and VGLUT2 have been reported to show complementary distributions in most brain regions and have been assumed to define distinct functional elements. In the present study, we first investigated the expression of VGLUT1 and VGLUT2 in the trigeminal sensory nuclear complex of the rat by dual-fluorescence in situ hybridization. Although VGLUT1 and/or VGLUT2 mRNA signals were detected in all the nuclei, colocalization was found only in the principal sensory trigeminal nucleus (Vp). About 64% of glutamatergic Vp neurons coexpressed VGLUT1 and VGLUT2, and the others expressed either VGLUT1 or VGLUT2, indicating that Vp neurons might be divided into three groups. We then injected retrograde tracer into the thalamic regions, including the posteromedial ventral nucleus (VPM) and posterior nuclei (Po), and observed that the majority of both VGLUT1- and VGLUT2-expressing Vp neurons were retrogradely labeled with the tracer. We further performed anterograde labeling of Vp neurons and observed immunoreactivies for anterograde tracer, VGLUT1, and VGLUT2 in the VPM and Po. Most anterogradely labeled axon terminals showed immunoreactivities for both VGLUT1 and VGLUT2 in the VPM and made asymmetric synapses with dendritic profiles of VPM neurons. On the other hand, in the Po, only a few axon terminals were labeled with anterograde tracer, and they were positive only for VGLUT2. The results indicated that Vp neurons expressing VGLUT1 and VGLUT2 project to the VPM, but not to the Po, although the functional differences of three distinct populations of Vp neurons, VGLUT1-, VGLUT2-, and VGLUT1/VGLUT2-expressing ones, remain unsettled.
In this article typos have been corrected:1. Consistently, the protective effects of FNDC5 on mitochondrial bioenergetics were counteracted in SIRT3 cKO mice.2. Figure legends: Fig. 1: a, Serum irisin levels were decreased in patients with poor outcomes compared to those with good outcomes (P < 0.001).3. The sentence 'while there is no obvious change of acetylation level in DRP1' has been deleted.4. Fig. 2: the MRI scan of the brain in the bottom panels of Fig. 2b were incorrect due to the mistaken images being inadvertently inserted during the assembly of Fig. 2 (separate attachments in e-mail named original Fig. 2 and amended Fig. 2).
Glioblastoma multiforme (GBM) is an aggressive brain tumor with a rather short survival time. Mutation of p53 has been observed and reported to play critical roles in the progression of GBM. However, the pathological mechanisms are still unclear. This study was designed to identify the role of miR-154 in mediating the biological functions of p53 in glioblastoma multiforme.In the current study, the expression of miR-154 in GBM tissue samples and cell lines with wt-p53 or mutant p53 was evaluated. The functions of miR-154 in tumor migration, invasion and epithelial-mesenchymal transition were analyzed in vitro. A luciferase reporter assay was used to identify the target of miR-154.We found that expression of miR-154 was much lower in patient tissues with mutant p53. Further study revealed that p53 was a transcription factor of miR-154 and that the R273H mutation led to its inactivation. In addition, overexpression of miR-154 remarkably suppressed cell migration, invasion and EMT in vitro and tumor growth in vivo. Moreover, TCF12 was proven to be a direct target of miR-154, and the tumor suppressive effect of miR-154 was reversed by TCF12.Overall, miR-154, which was regulated by wt-p53, inhibited migration, invasion and EMT of GBM cells by targeting TCF12, indicating that miR-154 may act as a biomarker and that the p53/miR-154/TCF12 pathway could be a potential therapeutic target for GBM.
Rationale: Neuroadaptations in the medial prefrontal cortex (mPFC) and Nucleus Accumbens (NAc) play a role in the disruption of control-reward circuits in opioid addiction.Small Conductance Calcium-Activated Potassium (SK) channels in the mPFC have been implicated in neuronal excitability changes during morphine withdrawal.However, the mechanism that modulates SK channels during withdrawal is still unknown.Methods: Rats were exposed for one week to daily morphine injections (10 mg•kg -1 s.c.) followed by conditional place preference (CPP) assessment.One week after withdrawal, electrophysiological, morphological and molecular biological methods were applied to investigate the effects of morphine on SK channels in mPFC, including infralimbic (IL), prelimbic (PrL) cortices and NAc (core and shell).We verified the hypothesis that Rac1, a member of Rho family of small GTPases, implicated in SK channel regulation, modulate SK channel neuroadaptations during opiate withdrawal.Results: One week after morphine withdrawal, the neuronal excitability of layer 5 pyramidal neurons in IL was decreased, but not in PrL.Whereas, the excitability was increased in NAc-shell, but not in NAc-core.In mPFC, the expression of the SK3 subunit was enhanced after one-week of withdrawal compared to controls.In the IL, Rac1 signaling was increased during withdrawal, and the Rac1 inhibitor NSC23766 disrupted SK current, which increased neuronal firing.Suppression of Rac1 inhibited morphine-induced CPP and expression of SK channels in IL.Conclusions: These findings highlight the potential value of SK channels and the upstream molecule Rac1, which may throw light on the therapeutic mechanism of neuromodulation treatment for opioid dependence.
Drug addiction can be considered as a metabolic disease because it is triggered by the disruption of metabolism and causes persistent neurochemical disorders that lead to addiction. The purpose of this study was to identify the potential brain biomarkers and the molecular mechanisms in cocaine-induced behavioral sensitization for self-administering rats. UHPLC-MS/MS targeted metabolomics was used to measure 23 neurotransmitters metabolites which may serve as the biological indices underlying the mechanisms of cocaine-induced behavioral sensitization for the key nuclei of brain reward circuits in the process of cocaine addiction. The measurement results showed that there were many changes for many neurotransmitters metabolites in the key nuclei of brain reward circuits (the striatum, the NAc, the hippocampus, the PFC, etc.), but there was no change in the cerebellum during the reconsolidation of drug addiction memory. These findings strongly indicated that many neurotransmitter metabolites in above key nuclei of brain reward circuits participated in cocaine-induced behavioral sensitization for self-administering rats. And it may contribute to a better understanding of metabolic changes in the process of cocaine-induced behavioral sensitization and to be helpful to provide a more integrated view of the molecular underpinnings and to ultimately find biomarkers to assist clinical diagnosis and treatment.
Objective Traumatic brain injury (TBI) is a global social, economic, and health challenge that is associated with premature death and long-term disability. In the context of rapid development of urbanization, the analysis of TBI rate and mortality trend could provide abundant diagnosis and treatment suggestions, which helps to form future reference on public health strategies. Methods In this study, as one of major neurosurgical centers in China, we focused on the regime shift of TBI based on 18-year consecutive clinical data and evaluated the epidemiological features. In our current study, a total of 11,068 TBI patients were reviewed. Results The major cause of TBI was road traffic injuries (44.%), while the main type of injury was cerebral contusion ( n = 4,974 [44.94%]). Regarding to temporal changes, a decreasing trend in TBI incidence for patients under 44 years old was observed, while an increasing trend for those aged over 45 years was indicated. Incidences of RTI and assaults decreased, while ground level fall presented increasing incidences. The total number of deaths was 933 (8.43%), with a decreasing trend in overall mortality since 2011. Age, cause of injury, GCS at admission, Injury Severity Score, shock state at admission, trauma-related diagnoses and treatments were significantly associated with mortality. A predictive nomogram model for poor prognosis was developed based on patient's GOS scores at discharge. Conclusions The trends and characteristics of TBI patients changed with rapid development of urbanization in the past 18 years. Further larger studies are warranted to verify its clinical suggestions.
The aim of the present study was to examine the relapse time and analyse the social, psychological and physical factors related to relapse among drugdependent patients who had undergone neurosurgery by ablating the nucleus accumbens (NAc surgical group) and those who had undergone detoxification with non-operative treatment in residential compulsory rehabilitation centres (control group). A total of 100 patients from the NAc surgical group and 92 patients from the control group were recruited in the study for 5 years. Information regarding their experiences of previous abstinence from drug use and the relapse time was obtained by interviews, while the relapse reasons were obtained through questionnaire. The study shows that there is a significant correlation in relapse reasons between the two groups. 'Relief from disturbance' (psychological factor) and 'peer influence' (social factor) were the two main factors associated with relapse. Factors like 'desire for last use' and 'boredom' (psychological factor) were more associated with relapse in the control group than the NAc surgical group. At 5 years post-operation, the number of patients in the employment and married status in non-relapse group was significantly higher than in the relapse group. There was also a statistical difference in the 5-year survival rate between them. The average relapse time was the first three years. Thus prevention of relapse to drug dependence after detoxification, especially for those with NAc surgery should be improved to focus on the main factors and time.
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