Reelin Controls Progenitor Cell Migration in the Healthy and Pathological Adult Mouse Brain

Understanding the signals that control migration of neural progenitor cells in the adult brain may provide new therapeutic opportunities. Reelin is best known for its role in regulating cell migration during brain development, but we now demonstrate a novel function for reelin in the injured adult brain. First, we show that Reelin is upregulated around lesions. Second, experimentally increasing Reelin expression levels in healthy mouse brain leads to a change in the migratory behavior of subventricular zone-derived progenitors, triggering them to leave the rostral migratory stream (RMS) to which they are normally restricted during their migration to the olfactory bulb. Third, we reveal that Reelin increases endogenous progenitor cell dispersal in periventricular structures independently of any chemoattraction but via cell detachment and chemokinetic action, and thereby potentiates spontaneous cell recruitment to demyelination lesions in the corpus callosum. Conversely, animals lacking Reelin signaling exhibit reduced endogenous progenitor recruitment at the lesion site. Altogether, these results demonstrate that beyond its known role during brain development, Reelin is a key player in post-lesional cell migration in the adult brain. Finally our findings provide proof of concept that allowing progenitors to escape from the RMS is a potential therapeutic approach to promote myelin repair

Rise and Demise of Bioinformatics? Promise and Progress

The field of bioinformatics and computational biology has gone through a number of transformations during the past 15 years, establishing itself as a key component of new biology. This spectacular growth has been challenged by a number of disruptive changes in science and technology. Despite the apparent fatigue of the linguistic use of the term itself, bioinformatics has grown perhaps to a point beyond recognition. We explore both historical aspects and future trends and argue that as the field expands, key questions remain unanswered and acquire new meaning while at the same time the range of applications is widening to cover an ever increasing number of biological disciplines. These trends appear to be pointing to a redefinition of certain objectives, milestones, and possibly the field itself

Evidence of causal effect of major depression on alcohol dependence: findings from the psychiatric genomics consortium

BACKGROUND Despite established clinical associations among major depression (MD), alcohol dependence (AD), and alcohol consumption (AC), the nature of the causal relationship between them is not completely understood. We leveraged genome-wide data from the Psychiatric Genomics Consortium (PGC) and UK Biobank to test for the presence of shared genetic mechanisms and causal relationships among MD, AD, and AC. METHODS Linkage disequilibrium score regression and Mendelian randomization (MR) were performed using genome-wide data from the PGC (MD: 135 458 cases and 344 901 controls; AD: 10 206 cases and 28 480 controls) and UK Biobank (AC-frequency: 438 308 individuals; AC-quantity: 307 098 individuals). RESULTS Positive genetic correlation was observed between MD and AD (rgMD−AD = + 0.47, P = 6.6 × 10−10). AC-quantity showed positive genetic correlation with both AD (rgAD−AC quantity = + 0.75, P = 1.8 × 10−14) and MD (rgMD−AC quantity = + 0.14, P = 2.9 × 10−7), while there was negative correlation of AC-frequency with MD (rgMD−AC frequency = −0.17, P = 1.5 × 10−10) and a non-significant result with AD. MR analyses confirmed the presence of pleiotropy among these four traits. However, the MD-AD results reflect a mediated-pleiotropy mechanism (i.e. causal relationship) with an effect of MD on AD (beta = 0.28, P = 1.29 × 10−6). There was no evidence for reverse causation. CONCLUSION This study supports a causal role for genetic liability of MD on AD based on genetic datasets including thousands of individuals. Understanding mechanisms underlying MD-AD comorbidity addresses important public health concerns and has the potential to facilitate prevention and intervention efforts

Electroconvulsive therapy in Parkinson´s disease

Purpose To analyze the effectiveness of electroconvulsive therapy for the management of depression and/or psychosis refractory to drug therapy in patients with Parkinson disease.Methods A retrospective study was carried out including patients treated with electroconvulsive therapy during the period between 2002 and 2013. A review of the literature was performed.Results A total of 27 patients were included. In regards to the neuropsychiatric diagnosis, 14 patients had major depression, 12 patients had both psychosis and depression, and only one patient had isolated psychosis. The mean number of electroconvulsive therapy sessions was 12 ± 2.8. After electroconvulsive therapy, all patients showed a statistically significant improvement in the Brief Psychiatric Rating scale (reduction of 52% points) and Hamilton Depression Rating Scale (reduction of 50% points) independent of the presence of psychosis, depression or both.Conclusion Electroconvulsive therapy is effective for the treatment of refractory neuropsychiatric symptoms in Parkinson’s disease

Desigualdades contextuais e individuais da prevalencia de dor dentaria em adultos e idosos no Brasil

Abstract published in English and Portuguese English title: Contextual and individual inequalities in dental pain prevalence among Brazilian adults and eldersThis study aimed to assess the prevalence of dental pain among adults and older people living in Brazil’s State capitals. Information was gathered from the Telephone Survey Surveillance System for Risk and Protective Factors for Chronic Diseases (VIGITEL) in 2009 (n = 54,367). Dental pain was the outcome. Geographic region, age, gender, race, schooling, private health coverage, smoking, and soft drink consumption were the explanatory variables. Multilevel Poisson regression models were performed. Prevalence of dental pain was 15.2%; Macapá and São Luís had prevalence rates greater than 20%; all capitals in the South and Southeast, plus Cuiabá, Campo Grande, Maceió, Recife, and Natal had prevalence rates less than 15%. Factors associated with increased prevalence of dental pain were the North and Northeast regions, female gender, black/brown skin color, lack of private health insurance, smoking, and soft drink consumption. Dental pain is a public health problem that should be monitored by health surveillance systems. = O objetivo deste estudo foi conhecer a prevalência de dor dentária e fatores associados em adultos e idosos residentes nas capitais brasileiras usando os dados do Sistema de Vigilância de Fatores de Risco e Proteção para Doenças Crônicas por Inquérito Telefônico (VIGITEL), de 2009 (n = 54.367). Dor dentária foi a variável dependente. Macrorregião, idade, sexo, raça, escolaridade, posse de plano de saúde, tabagismo e consumo de refrigerantes foram as variáveis exploratórias. Foram realizadas regressões de Poisson multinível. A prevalência de dor dentária foi de 15,2%; Macapá e São Luís apresentaram prevalências maiores que 20% enquanto em todas as capitais do Sul e Sudeste, em Cuiabá, Campo Grande, Maceió, Recife e Natal foram encontradas prevalências menores que 15%. Residentes no Norte e Nordeste, mulheres, pretos e pardos, aqueles que não possuem plano de saúde, tabagistas e consumidores de refrigerantes apresentaram as maiores prevalências de dor dentária. A dor dentária é um problema de saúde pública que deve ser monitorado pelos sistemas de vigilância em saúde.Marco A. Peres, Betine Pinto Moehlecke Iser, Karen Glazer Peres, Deborah Carvalho Malta, José Leopoldo Ferreira Antune

Cerebellar hypoplasia, with quadrupedal locomotion, caused by mutations in the very low-density lipoprotein receptor gene

The cerebellum is the primary motor coordination centre of the central nervous system. Lesions or congenital defects of the cerebellum cause incoordination of the muscles resulting in irregular gait and falling. Recently, we reported a large family with cerebellum hypoplasia and quadrupedal locomotion as a recessive trait, which we mapped to chromosome 17p13. We identified one additional family with the same condition and mapped the underlying gene to a 14-cM interval on chromosome 9ptel using a genome-wide linkage approach. Sequencing of candidate genes identified a homozygous frameshift mutation in the very low-density lipoprotein receptor (VLDLR) gene in all affected individuals. The association of cerebellar hypoplasia with mutations in VLDLR has been reported previously in the Hutterite population and in a family from Iran. However, quadrupedal locomotion was never observed indicating that environmental factors play a major role in the pathogenesis of this form of locomotion