Neuropeptide S-Mediated Facilitation of Synaptic Transmission Enforces Subthreshold Theta Oscillations within the Lateral Amygdala

The neuropeptide S (NPS) receptor system modulates neuronal circuit activity in the amygdala in conjunction with fear, anxiety and the expression and extinction of previously acquired fear memories. Using in vitro brain slice preparations of transgenic GAD67-GFP (Δneo) mice, we investigated the effects of NPS on neural activity in the lateral amygdala as a key region for the formation and extinction of fear memories. We are able to demonstrate that NPS augments excitatory glutamatergic synaptic input onto both projection neurons and interneurons of the lateral amygdala, resulting in enhanced spike activity of both types of cells. These effects were at least in part mediated by presynaptic mechanisms. In turn, inhibition of projection neurons by local interneurons was augmented by NPS, and subthreshold oscillations were strengthened, leading to their shift into the theta frequency range. These data suggest that the multifaceted effects of NPS on amygdaloid circuitry may shape behavior-related network activity patterns in the amygdala and reflect the peptide's potent activity in various forms of affective behavior and emotional memory

A novel approach of homozygous haplotype sharing identifies candidate genes in autism spectrum disorder

Autism spectrum disorder (ASD) is a highly heritable disorder of complex and heterogeneous aetiology. It is primarily characterized by altered cognitive ability including impaired language and communication skills and fundamental deficits in social reciprocity. Despite some notable successes in neuropsychiatric genetics, overall, the high heritability of ASD (~90%) remains poorly explained by common genetic risk variants. However, recent studies suggest that rare genomic variation, in particular copy number variation, may account for a significant proportion of the genetic basis of ASD. We present a large scale analysis to identify candidate genes which may contain low-frequency recessive variation contributing to ASD while taking into account the potential contribution of population differences to the genetic heterogeneity of ASD. Our strategy, homozygous haplotype (HH) mapping, aims to detect homozygous segments of identical haplotype structure that are shared at a higher frequency amongst ASD patients compared to parental controls. The analysis was performed on 1,402 Autism Genome Project trios genotyped for 1 million single nucleotide polymorphisms (SNPs). We identified 25 known and 1,218 novel ASD candidate genes in the discovery analysis including CADM2, ABHD14A, CHRFAM7A, GRIK2, GRM3, EPHA3, FGF10, KCND2, PDZK1, IMMP2L and FOXP2. Furthermore, 10 of the previously reported ASD genes and 300 of the novel candidates identified in the discovery analysis were replicated in an independent sample of 1,182 trios. Our results demonstrate that regions of HH are significantly enriched for previously reported ASD candidate genes and the observed association is independent of gene size (odds ratio 2.10). Our findings highlight the applicability of HH mapping in complex disorders such as ASD and offer an alternative approach to the analysis of genome-wide association data

Efeito de um programa de condicionamento físico no broncoespasmo induzido pelo exercício em mulheres obesas Effect of a physical fitness program on the exercise-induced bronchospasm in obese women

O broncoespasmo induzido pelo exercício físico (BIE) é uma síndrome clínica caracterizada pelo estreitamento brônquico e ocorre mais frequentemente em indivíduos obesos. OBJETIVO: Avaliar o possível efeito de um programa de condicionamento físico em relação ao BIE em mulheres obesas. MÉTODOS: Trinta e duas mulheres foram divididas em três grupos: grupo A (obesidade ou sobrepeso + treinamento físico), grupo B (obesidade ou sobrepeso) e grupo C (controle). Foi aplicado um teste de caminhada de seis minutos antes e após um período de 12 semanas. O BIE foi verificado por meio de um monitor de pico de fluxo expiratório após a aplicação do teste de caminhada. Durante essas 12 semanas, para o grupo A um programa de atividade física foi conduzido três vezes por semana e cada sessão de 60 minutos foi composta por 10 minutos de alongamento, seguidos por 30 de exercícios aeróbios (50% da frequência cardíaca de reserva como intensidade), 15 de exercícios de força de baixa intensidade e cinco de relaxamento e alongamento. RESULTADOS: O programa de treinamento físico causou aumento significativo no pico de fluxo expiratório mínimo após o teste de esforço (pré: 379 ± 16l/min; pós: 405 ± 12l/min; p < 0,05) e reduziu em 50% (33% para 17%) a proporção de mulheres que apresentou BIE (p < 0,05). CONCLUSÃO: O programa de condicionamento físico de 12 semanas foi capaz de melhorar a função respiratória de mulheres obesas.<br>Exercise-induced bronchospasm (EIB) is a syndrome characterized by reduced bronchial lumen and happens more often in obese subjects. OBJECTIVE: To evaluate the possible effect of an exercise training program on EIB in obese women. METHODS: 32 women were divided in three groups: group A (obesity + exercise training), group B (obesity) and group C (control). A six-minute walking test was applied before and after 12 weeks. EIB was measured through a monitor of peak of expiratory flow used after the application of the walking test. During the12 weeks, an exercise training program was delivered to group A, three times a week, 60 minutes a day. Each exercise session consisted of 10 minutes of stretching exercises, followed by 30 minutes of aerobic exercise (50% of reserve heart rate as intensity), 15' of low-intensity strength training and 5' of stretching and relaxing exercises. RESULTS: Exercise training significantly increased minimum peak of expiratory flow after the walking test (before: 379±16 l/min; after: 405±12 l/min; p<0.05) and reduced in 50% (33% to 17%) the proportion of women who presented EIB (p<0.05). CONCLUSION: The 12-week exercise training increased the respiratory function of obese women