Replication of functional serotonin receptor type 3A and B variants in bipolar affective disorder: a European multicenter study

Serotonin type 3 receptors (5-HT3) are involved in learning, cognition and emotion, and have been implicated in various psychiatric phenotypes. However, their contribution to the pathomechanism of these disorders remains elusive. Three single nucleotide polymorphisms (SNPs) in the HTR3A and HTR3B genes (rs1062613, rs1176744 and rs3831455) have been associated with bipolar affective disorder (BPAD) in pilot studies, and all of them are of functional relevance. We performed a European multicenter study to confirm previous results and provide further evidence for the relevance of these SNPs to the etiology of neuropsychiatric disorders. This involved analysis of the distribution of the three SNPs among 1804 BPAD cases and 2407 healthy controls. A meta-analysis revealed a pooled odds ratio of 0.881 (P=0.009, 95% confidence intervals=0.802–0.968) for the non-synonymous functional SNP HTR3B p.Y129S (rs1176744), thereby confirming previous findings. In line with this, the three genome-wide association study samples BOMA (Bonn-Mannheim)-BPAD, WTCCC (Wellcome Trust Case Control Consortium)-BPAD and GAIN (Genetic Association Information Network)-BPAD, including >3500 patients and 5200 controls in total, showed an overrepresentation of the p.Y129 in patients. Remarkably, the meta-analysis revealed a P-value of 0.048 (OR=0.934, fixed effect model). We also performed expression analyses to gain further insights into the distribution of HTR3A and HTR3B mRNA in the human brain. HTR3A and HTR3B were detected in all investigated brain tissues with the exception of the cerebellum, and large differences in the A:B subunit ratio were observed. Interestingly, expression of the B subunit was most prominent in the brain stem, amygdalae and frontal cortex, regions of relevance to psychiatric disorders. In conclusion, the present study provides further evidence for the presence of impaired 5-HT3 receptor function in BPAD

Poziome przesłony przeciwfiltracyjne

W ciągu ostatnich 20 lat w Polsce wyraźnie zaznaczyła się tendencja do umieszczania coraz głębiej podziemnej części budynków. W przypadku budynków w gęstej zabudowie miejskiej wynika to wprost z konieczności maksymalnego wykorzystania działki budowlanej dla otrzymania jak największej powierzchni użytkowej budynku

Pegada Ecológica: uma ferramenta utilizada como indicador e conscientizador do consumo, aplicado na UNG Universidade, Guarulhos/SP

<p>Among the functions of a university there are Teaching, Research and Extension. In order to collaborate in the extension of actions within the week of Conscious Consumption, 2016, Master in Geoenvironmental Analysis at the UNG Universidade suggested the questionnaire on the Ecological Footprint, an instrument that was developed and widely publicized by the WWF-Brazil (World Wide Fund for Nature - Brazil). The shares were held in the three campuses in the University: Center, Dutra and Itaquaquecetuba, covering about 1,000 students. Students answered the questionnaire with 18 questions and after the addition of the points, these might be classified according to the amount of renewable natural resources to maintain their standard of living and how many planets would be needed to keep this consumption if all people on the planet I had the same level of consumption. With the result of the application of this questionnaire, we can see that the students of the UNG Universidade need, on average, 2.8 planets to maintain its consumption of life, higher than the national average which is 1.6 and very close to average the UK is 3.0. When it comes to Conscious Consumption it is important each person doing the exercise to quantify and reflect on their lifestyle. Thus, this extension activity fulfilled its objectives, since the discussion on consumption was noticeable by observing the students talking and checking how are consumerist and Consumer Awareness is not limited to “shopping” but also housing, food, waste and transportation.</p

The ventromedial hypothalamus mediates predator fear memory.

The amygdala has been shown to be essential for the processing of acute and learned fear across animal species. However, the downstream neural circuits that mediate these fear responses differ according to the nature of the threat, with separate pathways having been identified for predator, conspecific and physically harmful threats. In particular, the dorsomedial part of the ventromedial hypothalamus (VHMdm) is critical for the expression of defensive responses to predators. Here, we tested the hypothesis that this circuit also participates in predator fear memory by transient pharmacogenetic inhibition of the VMHdm and its downstream effector, the dorsal periaqueductal grey, during predator fear learning in the mouse. Our data demonstrate that neural activity in the VMHdm is required for both the acquisition and recall of predator fear memory, whereas that of its downstream effector, the dorsal periaqueductal grey, is required only for the acute expression of fear. These findings are consistent with a role for the medial hypothalamus in encoding an internal emotional state of fear

High-frequency HTR3B variant associated with major depression dramatically augments the signaling of the human 5-HT3AB receptor

The 5-hydroxytryptamine-3 (5-HT3) receptor mediates the fast excitatory neurotransmission of serotonin and is known to mediate the nausea/emesis induced by radio/chemotherapy and anesthetics. A polymorphism encoding the variation Y129S in the 5-HT3B subunit exists in high frequency in the general population and has been shown to be inversely correlated to the incidence of major depression in women. We show that 5-HT3AB(Y129S) receptors exhibit a substantially increased maximal response to serotonin compared with WT receptors in two fluorescence-based cellular assays. In electrophysiological recordings, the deactivation and desensitization kinetics of the 5-HT3AB(Y129S) receptor are 20- and 10-fold slower, respectively, than those of the WT receptor. Single-channel measurements reveal a 7-fold-increased mean open time of 5-HT3AB(Y129S) receptors compared with WT receptors. The augmented signaling displayed by 5-HT3AB(Y129S) receptors may confer protection against the development of depression. The variant also may influence the development and/or treatment of nausea and other disorders involving 5-HT3 receptors. Thus, the impact of the high-frequency variant 5-HT3B(Y129S) on 5-HT3AB receptor signaling calls for a search for additional phenotypes, and the variant may thus aid in establishing the role of the 5-HT3AB receptor in pathophysiology