Mechanism of the medium‐duration afterhyperpolarization in rat serotonergic neurons

Most serotonergic neurons display a prominent medium‐duration afterhyperpolarization (mAHP), which is mediated by small‐conductance Ca²⁺‐activated K⁺ (SK) channels. Recent ex vivo and in vivo experiments have suggested that SK channel blockade increases the firing rate and/or bursting in these neurons. The purpose of this study was therefore to characterize the source of Ca²⁺ which activates the mAHP channels in serotonergic neurons. In voltage‐clamp experiments, an outward current was recorded at ?60 mV after a depolarizing pulse to +100 mV. A supramaximal concentration of the SK channel blockers apamin or (‐)‐bicuculline methiodide blocked this outward current. This current was also sensitive to the broad Ca²⁺ channel blocker Co²⁺ and was partially blocked by both ω‐conotoxin and mibefradil, which are blockers of N‐type and T‐type Ca²⁺ channels, respectively. Neither blockers of other voltage‐gated Ca²⁺ channels nor DBHQ, an inhibitor of Ca²⁺‐induced Ca²⁺ release, had any effect on the SK current. In current‐clamp experiments, mAHPs following action potentials were only blocked by ω‐conotoxin and were unaffected by mibefradil. This was observed in slices from both juvenile and adult rats. Finally, when these neurons were induced to fire in an in vivo‐like pacemaker rate, only ω‐conotoxin was able to increase their firing rate (by ~30%), an effect identical to the one previously reported for apamin. Our results demonstrate that N‐type Ca²⁺ channels are the only source of Ca²⁺ which activates the SK channels underlying the mAHP. T‐type Ca²⁺ channels may also activate SK channels under different circumstances.     

Disentangling the influence of neighborhood and individual characteristics on early residential mobility among newly diagnosed patients with schizophrenia: a multilevel analysis

Purpose

Early residential mobility of schizophrenic patients may relate to discontinuity of treatment and adverse outcome. However, factors influencing early residential mobility of these patients are still poorly examined. The aim of this study was to disentangle the influence of individual and neighborhood characteristics on early residential mobility of schizophrenic patients.

Methods

The study used administrative data of 13, 400 individuals newly diagnosed with schizophrenia in Quebec between 2001 and 2002. These individuals were nested in 163 different health territories. Multilevel analyses were used to assess the contribution of individual and neighborhood characteristics on early residential mobility.

Results

The final model indicates that at the individual level, being men, wonder patients and physical comorbidity increased the likelihood of early residential mobility whereas older patients were less likely to migrate earlier. The health territory level explains about 7 % of the variation of early residential mobility and variables influencing residential mobility at this level are the fourth and the third quartiles of the population density.

Conclusions

Factors influencing early residential mobility of schizophrenic patients are located at both individual and neighborhood levels. This suggests that policies targeting only one-level factors are unlikely to significantly delays early residential mobility.     

Smoking behavior characteristics of non-selected smokers with childhood attention-deficit/hyperactivity disorder (AD/HD) history: a systematic review and meta-analysis

It is unclear whether adult smokers with childhood attention-deficit/hyperactivity disorder history (CH) have more severe smoking behavior than non-CH smokers, while it is clearly suggested that CH adolescents have more severe smoking behavior than CH adolescents. The aim of the present comprehensive meta-analysis is to determine whether CH smokers have more severe smoking behavior characteristics than those without and the effect of age on the association between CH and smoking behavior. We included all case–control studies and first round data collection of observational studies addressing the difference in smoking behavior characteristics of CH smokers versus non-CH smokers, with validated scales or structured interviews, without any language or date restriction. Nine studies (including 365 smokers with CH and 1,708 smokers without) were included. Compared to non-CH smokers, CH smokers smoked significantly more cigarettes [standardized mean differences (SMD) = 0.15, 95 % CI 0.01–0.28, p = 0.04] and began to regularly smoke earlier (SMD = ?0.28, 95 % CI ?0.49; ?0.07, p = 0.01) but were not significantly more nicotine dependent (SMD = 0.23, 95 % CI ?0.04 to 0.48, p = 0.08). After removing the single adolescent study, the significant association between CH and number of daily smoked cigarettes disappeared, and subgroups analyses confirmed that the significant association between CH and number of daily smoked cigarettes disappeared as age increased. Our meta-analysis illustrates a clinically important link between CH and tobacco smoking in adolescence but not later in life. Further high-quality studies are needed to confirm this finding, as only two studies included participants with a mean age below 20 years.     

Fetal intracranial hemorrhage related to maternal autoimmune thrombocytopenic purpura

Background

Maternal autoimmune thrombocytopenic purpura (AITP) can cause fetal intracranial hemorrhage.

Case report

A 19-year-old primigravida was referred to our institution for prenatally detected ventriculomegaly at 30th week of gestation. Her personal and family histories were unremarkable. Her platelet count was 54?×?109/L. Fetal neurosonography showed intraparenchymal hemorrhage. AITP was diagnosed in the mother and platelet count decreased at 34?×?109/L. Patient was treated with methylprednisolone and intravenous immunoglobulin. She delivered a 2,340-g infant at 37 weeks with elective cesarean section. The platelet count of the newborn was 181?×?109/L and coagulation tests were normal. No antiplatelet specific antibodies were detected in cord blood. Postnatal MRI evaluation confirmed grade IV intracranial hemorrhage. The newborn baby has suffered from mild spasticity and seizures.

Conclusions

Clinicians must be vigilant about the catastrophic fetal complications of maternal AITP; a close follow-up with a multidisciplinary cooperation between obstetricians, hematologists, and neonatologists must be warranted.     

Impaired brain energy metabolism in the BACHD mouse model of Huntington's disease: critical role of astrocyte–neuron interactions

Huntington''s disease (HD) is caused by cytosine-adenine-guanine (CAG) repeat expansions in the huntingtin (Htt) gene. Although early energy metabolic alterations in HD are likely to contribute to later neurodegenerative processes, the cellular and molecular mechanisms responsible for these metabolic alterations are not well characterized. Using the BACHD mice that express the full-length mutant huntingtin (mHtt) protein with 97 glutamine repeats, we first demonstrated localized in vivo changes in brain glucose use reminiscent of what is observed in premanifest HD carriers. Using biochemical, molecular, and functional analyses on different primary cell culture models from BACHD mice, we observed that mHtt does not directly affect metabolic activity in a cell autonomous manner. However, coculture of neurons with astrocytes from wild-type or BACHD mice identified mutant astrocytes as a source of adverse non-cell autonomous effects on neuron energy metabolism possibly by increasing oxidative stress. These results suggest that astrocyte-to-neuron signaling is involved in early energy metabolic alterations in HD.     

The efficiency of glutamate uptake differs between neonatal and adult cortical microvascular endothelial cells

Glutamate transporters (excitatory amino-acid transporters (EAATs)) are essential for brain homeostasis. While previous studies indicate that the vascular endothelium contributes to glutamate efflux in the adult brain, little information is available regarding glutamate uptake in the immature brain. The present study shows a differential expression pattern of EAATs between cortical microvessels in adults and newborns. In addition, adult cortical endothelial cells take up glutamate more efficiently than neonatal cells. Our findings indicate age-specific changes in extracellular glutamate regulation by brain endothelial cells, suggesting differences in the efficiency of glutamate efflux during an excitotoxic process that, in turn, may contribute to age-specific brain vulnerability.     

Effects of Cognitive–Behavioral Conjoint Therapy for PTSD on Partners’ Psychological Functioning

A number of studies have documented that posttraumatic stress disorder (PTSD) symptoms in “one” partner are negatively associated with their intimate partner's psychological functioning. The present study investigated intimate partners’ mental health outcomes (i.e., depression, anxiety, and anger) in a sample of 40 partners of individuals with PTSD within a randomized waitlist controlled trial of cognitive–behavioral conjoint therapy for PTSD (Monson & Fredman, 2012 ). There were no significant differences between active treatment and waitlist in intimate partners’ psychological functioning at posttreatment. Subgroup analyses, however, of partners exhibiting clinical levels of distress at pretreatment on several measures showed reliable and clinically significant improvements in their psychological functioning at posttreatment and no evidence of worsening. Results suggest that cognitive–behavioral conjoint therapy for PTSD may have additional benefits for partners presenting with psychological distress.