Increased locomotor activity via regulation of GABAergic signalling in foxp2 mutant zebrafish—implications for neurodevelopmental disorders

Recent advances in the genetics of neurodevelopmental disorders (NDDs) have identified the transcription factor FOXP2 as one of numerous risk genes, e.g. in autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). FOXP2 function is suggested to be involved in GABAergic signalling and numerous studies demonstrate that GABAergic function is altered in NDDs, thus disrupting the excitation/inhibition balance. Interestingly, GABAergic signalling components, including glutamate-decarboxylase 1 (Gad1) and GABA receptors, are putative transcriptional targets of FOXP2. However, the specific role of FOXP2 in the pathomechanism of NDDs remains elusive. Here we test the hypothesis that Foxp2 affects behavioural dimensions via GABAergic signalling using zebrafish as model organism. We demonstrate that foxp2 is expressed by a subset of GABAergic neurons located in brain regions involved in motor functions, including the subpallium, posterior tuberculum, thalamus and medulla oblongata. Using CRISPR/Cas9 gene-editing we generated a novel foxp2 zebrafish loss-of-function mutant that exhibits increased locomotor activity. Further, genetic and/or pharmacological disruption of Gad1 or GABA-A receptors causes increased locomotor activity, resembling the phenotype of foxp2 mutants. Application of muscimol, a GABA-A receptor agonist, rescues the hyperactive phenotype induced by the foxp2 loss-of-function. By reverse translation of the therapeutic effect on hyperactive behaviour exerted by methylphenidate, we note that application of methylphenidate evokes different responses in wildtype compared to foxp2 or gad1b loss-of-function animals. Together, our findings support the hypothesis that foxp2 regulates locomotor activity via GABAergic signalling. This provides one targetable mechanism, which may contribute to behavioural phenotypes commonly observed in NDDs.

Interaction of School and Family in Teaching and Upbringing of Hyperactive Students of Educational Institutions

The article has generalized scientific views on the concept of hyperactivity, the main features of hyperactive behaviour, and the main elements of the system of the interaction between school and family when teaching and upbringing hyperactive students. Active development and personal stimulation of hyperactive students with the help of common work of their parents and teaching staff (partnership with a family) have been emphasized. The research has focused on the levels of parents’ involvement in partnership with the educational institution in the process of education and upbringing of hyperactive students: awareness and participation in school activities. The system of partnership between family and school in education and upbringing of hyperactive students as the purposeful influence of the school and social environment on each other, which promotes mutual enrichment, strengthening of educational potential of interacting systems, has been revealed. It has been defined that one of the main factors which help to engage parents in teaching hyperactive students is informing them about their children’s achievements. The level of teachers’ interest in success of such students, positive atmosphere at school and efforts put in the development of work with the parents, as well as the degree to which the parents are interested in their children’s success and in themselves as teachers of their own child are of great importance.

Fuzzy Protoform for Hyperactive Behaviour Detection Based on Commercial Devices

Hyperactive behaviour refers to a person making more movement than expected for his or her age and development, acting impulsively, and being easily distracted. There is a need to encourage early and reliable detection through the proposal of new methodologies and systems in the context of hyperactive behaviour to prevent or lessen related problems and disorders. This paper presents a methodology to compute a fuzzy protoform (a linguistic description) as an estimator for hyperactive behaviour. The proposed methodology is developed in a system called Smart HyBeDe, which integrate non-invasive and commercial wearable devices, such as activity bracelets, in order to capture data streams from inertial measurement units and optical heart rate sensors. The generated data by the wearable device are synchronized with a mobile device to process the fuzzy protoform to inform family members and professionals. Three datasets generated by the wearable device in real contexts are presented. These datasets are used to evaluate the impact of wrist choice for the wearable device, multiple fuzzy temporal windows, different aggregation operators, and relevant linguistic terms to define the fuzzy protoform as an estimator for the hyperactive behaviour. The results, analysed by a hyperactive behaviour expert, show that the proposed protoform is a suitable hyperactive behaviour estimator.

A molecular war: convergent and ontogenetic evidence for adaptive host manipulation in related parasites infecting divergent hosts

Mermithids (phylum Nematoda) and hairworms (phylum Nematomorpha) somehow drive their arthropod hosts into water, which is essential for the worms' survival after egression. The mechanisms behind this behavioural change have been investigated in hairworms, but not in mermithids. Establishing a similar mechanistic basis for host behavioural change between these two distantly related parasitic groups would provide strong convergent evidence for adaptive manipulation and insight into how these parasites modify and/or create behaviour. Here, we search for this convergence, and also contrast changes in physiology between hosts infected with immature and mature mermithids to provide the first ontogenetic evidence for adaptive manipulation by disentangling host response and pathology from the parasite's apparent manipulative effects. We used SWATH-mass spectrometry on brains of Forficula auricularia (earwig) and Bellorchestia quoyana (sandhopper), infected with the mermithids Mermis nigrescens and Thaumamermis zealandica , respectively, at both immature and mature stages of infection, to quantify proteomic changes resulting from mermithid infection. Across both hosts (and hairworm-infected hosts, from earlier studies), the general function of dysregulated proteins was conserved. Proteins involved in energy generation/mobilization were dysregulated, corroborating reports of erratic/hyperactive behaviour in infected hosts. Dysregulated proteins involved in axon/dendrite and synapse modulation were also common to all hosts, suggesting neuronal manipulation is involved in inducing positive hydrotaxis. Furthermore, downregulation of CamKII and associated proteins suggest manipulation of memory also contributes to the behavioural shift.

On the positive association between candy and fruit gum consumption and hyperactivity in children and adolescents with ADHD

Objective: The purpose of the present study was the analysis of the association between consumption of candy and fruit gums, diagnosis of attention deficit hyperactivity disorder (ADHD), and behavioural problems. Methods: In total, 1,187 children and adolescents of the German Health Interview and Examination Survey for Children and Adolescents (KiGGS) were analyzed. Results: It was observed that children and adolescents with ADHD as compared to healthy controls (HC) reported to consume more frequently and higher amounts of candy and fruit gums and that hyperactivity was associated with frequent candy and fruit gum consumption. Conclusions: Because with the present design no conclusions on causality or directionality of the found associations could be drawn, results are discussed quite broadly in the light of several previously published interpretations, also to serve as a generator for further research. One more innovative speculation is that children and adolescents with ADHD may consume more frequently candy and fruit gums in order i) to compensate for their higher needs of energy resulting from hyperactive behaviour and/or ii) to compensate for the ADHD-typical deficits in the “reward cascade”.