scholarly journals Precision medicine for the rescue of specific impairments in social behavior associated with the A350V Iqsec2 mutation

2020 ◽  
Author(s):  
Renad Jabarin ◽  
Nina Levy ◽  
Yasmin Abergel ◽  
Joshua H. Berman ◽  
Amir Zag ◽  
...  

AbstractIn this study we tested the hypothesis that precision medicine guided therapy targeting glutamatergic neurotransmission could rescue behavioral deficits exhibited by mice carrying a specific mutation in the Iqsec2 gene. The IQSEC2 protein plays a key role in glutamatergic synapses and mutations in the IQSEC2 gene are a frequent cause of neurodevelopmental disorders. We have recently reported on the molecular pathophysiology of one such mutation A350V and demonstrated that this mutation downregulates AMPA type glutamatergic receptors (AMPAR) in A350V mice. Here we sought to identify behavioral deficits in A350V mice and hypothesized that we could rescue these deficits by PF-4778574, a positive AMPAR modulator. We found that A350V Iqsec2 mice exhibit specific deficits in sex preference and emotional state preference behaviors as well as in vocalizations when encountering a female mouse. The social discrimination deficits, but not the impaired vocalization, were rescued with PF-4778574. We conclude that social behavior deficits associated with the A350V Iqsec2 mutation may be rescued by enhancing AMPAR mediated synaptic transmission.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Renad Jabarin ◽  
Nina Levy ◽  
Yasmin Abergel ◽  
Joshua H. Berman ◽  
Amir Zag ◽  
...  

AbstractIn this study we tested the hypothesis that pharmacological modulation of glutamatergic neurotransmission could rescue behavioral deficits exhibited by mice carrying a specific mutation in the Iqsec2 gene. The IQSEC2 protein plays a key role in glutamatergic synapses and mutations in the IQSEC2 gene are a frequent cause of neurodevelopmental disorders. We have recently reported on the molecular pathophysiology of one such mutation A350V and demonstrated that this mutation downregulates AMPA type glutamatergic receptors (AMPAR) in A350V mice. Here we sought to identify behavioral deficits in A350V mice and hypothesized that we could rescue these deficits by PF-4778574, a positive AMPAR modulator. Using a battery of social behavioral tasks, we found that A350V Iqsec2 mice exhibit specific deficits in sex preference and emotional state preference behaviors as well as in vocalizations when encountering a female mouse. The social discrimination deficits, but not the impaired vocalization, were rescued with a single dose of PF-4778574. We conclude that social behavior deficits associated with the A350V Iqsec2 mutation may be rescued by enhancing AMPAR mediated synaptic transmission.


2020 ◽  
Vol 75 (3) ◽  
pp. 425-454
Author(s):  
Hámori Eszter ◽  
Simon Réka Barbara ◽  
Márkus Lilla Viktória ◽  
Farkas Flóra

Háttér és célkitűzések:A fapofa-paradigma (Tronick, Als, Adamson, Wise és Brazelton 1978) szokatlan megszakításos helyzetet teremt az anya-csecsemő interakcióban, így az egyik leggyakrabban alkalmazott eljárás az egyéni és a diádikus társas és stressz-szabályozási minták vizsgálatában csecsemőkorban. A kódrendszerek sokfélesége miatt azonban ellentmondásosak az eredmények a mintázatok azonosításában. Jelen tanulmányban egyik célunk egy olyan globális kódrendszer kialakítása volt, amellyel külön vizsgálhatjuk a társas viselkedés és az érzelemkifejezés szerepét a regulációs mintázatok formálódásában. Másik célunk a fapofa- és a regulációs szakaszokra jellemző társasviselkedés-mintázatok keresése és a két szakasz közötti változásuk vizsgálata volt.Módszer:101 3–6 hónapos, tipikusan fejlődő csecsemő-anya párral vettük fel a fapofa-paradigmát. A csecsemők érzelmi állapotát, társas viselkedését és stressz-szintjének alakulását a jelen kutatásra kidolgozott Érzelmi és Társas Szabályozási Mintázatok Globális Kódrendszerével értékeltük a fapofa- és a regulációs szakaszokban.Eredmények:Az érzelmi dimenzió mintázatai egyértelműen mutatták a klasszikus fapofa-hatást a mintában. A társas dimenzióban négy fő mintázatot defi niáltunk: anyára pozitív, anyára negatív, anyára vegyes és minimalizáló. A fapofa-szakasz domináns társas mintázatai eltérően jósolták be a regulációs szakasz társas mintázatait. A társas viselkedés két szakasz közötti változásában a stressz-szinttel való összefüggésük mentén adaptív, rizikós és többesélyes mintázatokat azonosítottunk. Klaszterelemzéssel egy Nyugodt és egy Nyűgös csoport különült el, amiben az érzelmi dimenzió differenciáló szerepe emelkedett ki a társas dimenzióval szemben.Következtetések:Eredményeink alátámasztják, hogy már 3 hónapos kortól jelen lehetnek a stressz szabályozására specifi kus, egyéni regulációs mintázatok. Kódrendszerünk a globális dimenziók alkalmazásának fontosságára hívja fel a fi gyelmet, amely informálhat az összetett érzelmi, valamint a társasviselkedés-mintázatok és a stresszreguláció kölcsönkapcsolatáról, és így hozzájárulhat azok adaptív vagy maladaptív jellegének felméréséhez.Background and aims:The Face-to-Face-Still-Face Paradigm (FFSF, Tronick et al, 1978) artifi cially generates an unusual perturbation in the infant-mother interaction and as such has become a widely used procedure in the investigation of individual and dyadic social and stress regulation in infancy. The various coding systems, however, have brought about controversial results in the identifi cations of regulatory patterns. One of our aims was to develop a global coding system, by means of which the role of the social and emotional regulatory behaviors in the formations of organized regulatory patterns could be evaluated separately. Our second aim was to search for social behavior patterns exhibitive of the Still Face and Regulatory episodes as well as to examine their changes from one episode to to other.Method:The FFSF paradigm was administered to 101 typically developing 3-6 months-old infant-mother dyads. The emotional state, the social behavior and the changes in the stress level of the infant were evaluated in two episodes of the FFSFP by the Global Coding System of Emotional and Social Regulatory Patterns that has been developed for the purpose of this study.Results:The classical Still-Face effect has been clearly demonstrated by the results of the emotional state dimension. Beyond this, we identifi ed four social regulatory patterns: positive-to-mother, negative-to-mother, ambivalent-to-mother and minimization. The dominant social patterns in the Still-Face episode predicted variously those in the Reunion episode. Different patterns of the interrelations of the changes in social strategies and the stress level in the Reunion episode could be identifi ed as adaptive, risk and multi chance patterns. Two groups of infants have been separated by the cluster analysis, the calm and the fussy groups. Emotional dimension, as contrast to social dimension, has emerged as signifi cant clustering predictor. Conclusion: Our results support the hypotheses that individual stress regulatory patterns can be present from as early as three months of infant age. Our coding system draws attention to the importance of global behavioral coding dimensions that can inform us about the interconnection between the complex emotional and social behavior patterns and the stress regulation and thus can contribute to the exploration of their adaptive versus maladaptive nature.


Author(s):  
Ruha Benjamin

In this response to Terence Keel and John Hartigan’s debate over the social construction of race, I aim to push the discussion beyond the terrain of epistemology and ideology to examine the contested value of racial science in a broader political economy. I build upon Keel’s concern that even science motivated by progressive aims may reproduce racist thinking and Hartigan’s proposition that a critique of racial science cannot rest on the beliefs and intentions of scientists. In examining the value of racial-ethnic classifications in pharmacogenomics and precision medicine, I propose that analysts should attend to the relationship between prophets of racial science (those who produce forecasts about inherent group differences) and profits of racial science (the material-semiotic benefits of such forecasts). Throughout, I draw upon the idiom of speculation—as a narrative, predictive, and financial practice—to explain how the fiction of race is made factual, again and again. 


2019 ◽  
Vol 60 (2) ◽  
pp. 303-305
Author(s):  
Valdir Leite da Silva ◽  
José Cândido ◽  
José Nelson Campanha ◽  
Doraci R. de Oliveira ◽  
Carla Gheler-Costa ◽  
...  

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Kohei Kitagawa ◽  
Kensuke Matsumura ◽  
Masayuki Baba ◽  
Momoka Kondo ◽  
Tomoya Takemoto ◽  
...  

AbstractAutism spectrum disorder (ASD) is a highly prevalent neurodevelopmental disorder characterized by core symptoms of impaired social behavior and communication. Recent studies have suggested that the oxytocin system, which regulates social behavior in mammals, is potentially involved in ASD. Mouse models of ASD provide a useful system for understanding the associations between an impaired oxytocin system and social behavior deficits. However, limited studies have shown the involvement of the oxytocin system in the behavioral phenotypes in mouse models of ASD. We have previously demonstrated that a mouse model that carries the ASD patient-derived de novo mutation in the pogo transposable element derived with zinc finger domain (POGZWT/Q1038R mice), showed ASD-like social behavioral deficits. Here, we have explored whether oxytocin (OXT) administration improves impaired social behavior in POGZWT/Q1038R mice and found that intranasal oxytocin administration effectively restored the impaired social behavior in POGZWT/Q1038R mice. We also found that the expression level of the oxytocin receptor gene (OXTR) was low in POGZWT/Q1038R mice. However, we did not detect significant changes in the number of OXT-expressing neurons between the paraventricular nucleus of POGZWT/Q1038R mice and that of WT mice. A chromatin immunoprecipitation assay revealed that POGZ binds to the promoter region of OXTR and is involved in the transcriptional regulation of OXTR. In summary, our study demonstrate that the pathogenic mutation in the POGZ, a high-confidence ASD gene, impairs the oxytocin system and social behavior in mice, providing insights into the development of oxytocin-based therapeutics for ASD.


2021 ◽  
Vol 13 (2) ◽  
pp. 179-194
Author(s):  
Serene Ong ◽  
Jeffrey Ling ◽  
Angela Ballantyne ◽  
Tamra Lysaght ◽  
Vicki Xafis

AbstractGovernments are investing in precision medicine (PM) with the aim of improving healthcare through the use of genomic analyses and data analytics to develop tailored treatment approaches for individual patients. The success of PM is contingent upon clear public communications that engender trust and secure the social licence to collect and share large population-wide data sets because specific consent for each data re-use is impractical. Variation in the terminology used by different programmes used to describe PM may hinder clear communication and threaten trust. Language is used to create common understanding and expectations regarding precision medicine between researchers, clinicians and the volunteers. There is a need to better understand public interpretations of PM-related terminology. This paper reports on a qualitative study involving 24 focus group participants in the multi-lingual context of Singapore. The study explored how Singaporeans interpret and understand the terms ‘precision medicine’ and ‘personalised medicine’, and which term they felt more aptly communicates the concept and goals of PM. Results suggest that participants were unable to readily link the terms with this area of medicine and initially displayed preferences for the more familiar term of ‘personalised’. The use of visual aids to convey key concepts resonated with participants, some of whom then indicated preferences for the term ‘precision’ as being a more accurate description of PM research. These aids helped to facilitate dialogue around the ethical and social value, as well as the risks, of PM. Implications for programme developers and policy makers are discussed.


1973 ◽  
Vol 36 (3) ◽  
pp. 735-738 ◽  
Author(s):  
Joaquin F. Sousa-Poza ◽  
Robert Rohrberg ◽  
Ernest Shulman

Some characteristics of the social behavior of field-dependents as well as their superior recognition of ambiguous social stimuli led to the hypothesis that they would show greater self-disclosure than field-independents. This hypothesis was tested by administering the 60-item Jourard Self-disclosure Questionnaire (JSDQ) to 13 field-dependent and 13 field-independent Ss. In terms of total self-disclosure scores, field-dependents showed significantly (.025) higher levels than field-independents. Results are discussed in light of personality theories which emphasize the role of self-conceptual transactions in the development of the self.


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