The hippocampal dentate gyrus in the adult mammalian brain contains neural stem/progenitor cells (NS/PCs) capable of generating new neurons, i.e., neurogenesis. Most drugs of abuse examined to date decrease adult hippocampal neurogenesis, but the effects of cannabis (marijuana or cannabinoids) on hippocampal neurogenesis remain unknown. This study aimed at investigating the potential regulatory capacity of the potent synthetic cannabinoid HU210 on hippocampal neurogenesis and its possible correlation with behavioral change. We show that both embryonic and adult rat hippocampal NS/PCs are immunoreactive for CB1 cannabinoid receptors, indicating that cannabinoids could act on CB1 receptors to regulate neurogenesis. This hypothesis is supported by further findings that HU210 promotes proliferation, but not differentiation, of cultured embryonic hippocampal NS/PCs likely via a sequential activation of CB1 receptors, G i/o proteins, and ERK signaling. Chronic, but not acute, HU210 treatment promoted neurogenesis in the hippocampal dentate gyrus of adult rats and exerted anxiolytic-and antidepressant-like effects. X-irradiation of the hippocampus blocked both the neurogenic and behavioral effects of chronic HU210 treatment, suggesting that chronic HU210 treatment produces anxiolytic-and antidepressant-like effects likely via promotion of hippocampal neurogenesis.

Background-Diabetes is associated with increased risk of mortality as a consequence of acute myocardial infarction. This study determined whether rosiglitazone (ROSI) could reduce myocardial infarction after ischemia/reperfusion injury. Methods and Results-Male Lewis rats were anesthetized, and the left anterior descending coronary artery was ligated for 30 minutes. After reperfusion for 24 hours, the ischemic and infarct sizes were determined. ROSI at 1 and 3 mg/kg IV reduced infarct size by 30% and 37%, respectively (PϽ0.01 versus vehicle). Pretreatment with ROSI (3 mg · kg Ϫ1 · d

The tumor suppressor PTEN (phosphatase and tensin homolog deleted on chromosome 10) is a lipid and protein phosphatase. We report here that PTEN physically associates with the NR1 and NR2B subunits of NMDA receptors (NMDARs) in rat hippocampus. Downregulating the protein expression of PTEN inhibits the function of extrasynaptic NMDARs and decreases NMDAR surface expression, suggesting a crucial role for endogenous PTEN in the modulation of NMDAR-mediated neuronal function. Reducing PTEN expression also enhances Akt/Bad phosphorylation in hippocampal neurons. Importantly, suppressing lipid and protein phosphatase activity of PTEN, respectively, activates Akt and inhibits extrasynaptic NMDAR activity and thereby protects against ischemic neuronal death in vitro and in vivo. Thus, our study reveals a dual neuroprotective mechanism by which Akt/Bad and extrasynaptic NMDARs are regulated via downregulation of two distinct PTEN phosphatase activities and present the possibility of PTEN as a potential therapeutic target for stroke treatment.

The widespread distribution of the tumor suppressor PTEN (phosphatase and tensin homolog deleted on chromosome 10) in the adult brain suggests its role in a broad range of brain functions. Here we show evidence supporting a physical interaction of PTEN with a region in the third intracellular loop (3L4F) of the serotonin 5-HT2C receptor (5-HT2cR, formerly 5-HT1c receptor) in cell cultures. PTEN limits agonist-induced phosphorylation of 5-HT2cR through its protein phosphatase activity. We showed the probable existence of PTEN:5-HT2cR complexes in putative dopaminergic neurons in the rat ventral tegmental area (VTA), a brain region in which virtually all abused drugs exert rewarding effects by activating its dopamine neurons. We synthesized the interfering peptide Tat-3L4F, which is able to disrupt PTEN coupling with 5-HT2cR. Systemic application of Tat-3L4F or the 5-HT2cR agonist Ro600175 suppressed the increased firing rate of VTA dopaminergic neurons induced by delta9-tetrahydrocannabinol (THC), the psychoactive ingredient of marijuana. Using behavioral tests, we found that Tat-3L4F or Ro600175 blocks conditioned place preference of THC or nicotine, and that Ro600175, but not Tat-3L4F, produces anxiogenic effects, penile erection, hypophagia and motor functional suppression. These results suggest a potential strategy for treating drug addiction with the Tat-3L4F peptide.

BackgroundPrediction of the functional outcome for patients with convulsive status epilepticus (CSE) has been a challenge. The aim of this study was to characterize the prognostic factors and functional outcomes of patients after CSE in order to develop a practicable scoring system for outcome prediction.MethodsWe performed a retrospective explorative analysis on consecutive patients diagnosed with CSE between March, 2008 and November, 2014 in a tertiary academic medical center in northwest China. The modified Rankin Scale (mRS) was used to measure the functional outcome at three months post discharge.ResultsA total of 132 CSE patients was included, with a median age of 25.5 years and 60.6 % were male. Three months post discharge, an unfavorable outcome with mRS of 3–6 was seen in 62 (47.0 %) patients, 25 (18.9 %) of whom died. Logistic regression analysis revealed that encephalitis (p = 0.029), nonconvulsive SE (p = 0.018), diazepam resistance (p = 0.005), image abnormalities (unilateral lesions, p = 0.027; bilateral lesions or diffuse cerebral edema, p < 0.001) and tracheal intubation (p = 0.032) were significant independent predictors for unfavorable outcomes. Based on the coefficients in the model, these predictors were assigned a value of 1 point each, with the exception of the image, creating a 6-point scoring system, which we refer to as END-IT, for the outcome prediction of CSE. The area under the receiver operating characteristic curve for the END-IT score was 0.833 and using a cut-off point of 3 produced the highest sum sensitivity (83.9 %) and specificity (68.6 %). Compared with status epilepticus severity score (STESS) and Epidemiology-based Mortality score in SE (EMSE), END-IT score showed better discriminative power and predictive accuracy for the outcome prediction.ConclusionsWe developed an END-IT score with a strong discriminative power for predicting the functional outcome of CSE patients. External prospective validation in different cohorts is needed for END-IT score.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-016-1221-9) contains supplementary material, which is available to authorized users.