scholarly journals Regulation of Nav1.6-mediated sodium currents underlie the homeostatic control of neuronal intrinsic excitability in the optic tectum of the developing Xenopus laevis tadpole

2021 ◽  
Author(s):  
Adrian C Thompson ◽  
Carlos D Aizenman
Keyword(s):  
Synaptic Input ◽  
Developmental Disorders ◽  
Autism Spectrum ◽  
Homeostatic Plasticity ◽  
Intrinsic Excitability ◽  
Na Channel ◽  
Homeostatic Control ◽  
Na Currents ◽  
Circuit Development ◽  
Tectal Neurons

For individual neurons to function appropriately within a network that is undergoing synaptic reorganization and refinement due to developmental or experience-dependent changes in circuit activity, they must homeostatically adapt their intrinsic excitability to maintain a consistent output despite the changing levels of synaptic input. This homeostatic plasticity of excitability is particularly important for the development of sensory circuits, where subtle deficits in neuronal and circuit function cause developmental disorders including autism spectrum disorder and epilepsy. Despite the critical importance of this process for normal circuit development, the molecular mechanism by which this homeostatic control of intrinsic excitability is regulated is not fully understood. Here, we demonstrate that Xenopus optic tectal neurons express distinct fast, persistent and resurgent Na+ currents. Here, we demonstrate that Xenopus optic tectal neurons express distinct fast, persistent and resurgent Na+ currents. These are regulated with developmental changes in synaptic input, and homeostatically in response to changes in visual input. We show that expression of the voltage-gated Na+ channel subtype Nav1.6 is regulated with changes in intrinsic excitability, that blocking Nav1.6 channels is sufficient to decrease intrinsic excitability. Furthermore, that upregulation of Nav1.6 expression is necessary for experience-dependent increases in Na+ currents and intrinsic excitability. Finally, by examining behaviors that rely on visual and multisensory integration, we extend these findings to show that tight regulation of Na+ channel gene expression during a critical period of tectal circuit development is required for the normal functional development of the tectal circuitry.

scholarly journals Chromatin Remodeler CHD8 in Autism and Brain Development

2021 ◽  
Vol 10 (2) ◽  
pp. 366
Author(s):  
Anke Hoffmann ◽  
Dietmar Spengler
Keyword(s):  
Animal Studies ◽  
Mental Disease ◽  
Transgenic Animal ◽  
Autism Spectrum ◽  
Homeostatic Plasticity ◽  
Therapeutic Interventions ◽  
Model Organisms ◽  
Facial Dysmorphism ◽  
Transcriptional Level ◽  
Level Function

Chromodomain Helicase DNA-binding 8 (CHD8) is a high confidence risk factor for autism spectrum disorders (ASDs) and the genetic cause of a distinct neurodevelopmental syndrome with the core symptoms of autism, macrocephaly, and facial dysmorphism. The role of CHD8 is well-characterized at the structural, biochemical, and transcriptional level. By contrast, much less is understood regarding how mutations in CHD8 underpin altered brain function and mental disease. Studies on various model organisms have been proven critical to tackle this challenge. Here, we scrutinize recent advances in this field with a focus on phenotypes in transgenic animal models and highlight key findings on neurodevelopment, neuronal connectivity, neurotransmission, synaptic and homeostatic plasticity, and habituation. Against this backdrop, we further discuss how to improve future animal studies, both in terms of technical issues and with respect to the sex-specific effects of Chd8 mutations for neuronal and higher-systems level function. We also consider outstanding questions in the field including ‘humanized’ mice models, therapeutic interventions, and how the use of pluripotent stem cell-derived cerebral organoids might help to address differences in neurodevelopment trajectories between model organisms and humans.

scholarly journals Early Diagnostics and Early Intervention in Neurodevelopmental Disorders—Age-Dependent Challenges and Opportunities

2021 ◽  
Vol 10 (4) ◽  
pp. 861
Author(s):  
Mijna Hadders-Algra
Keyword(s):  
Early Intervention ◽  
High Risk ◽  
Early Detection ◽  
Developmental Disorders ◽  
Familial Risk ◽  
Brain Structures ◽  
Autism Spectrum ◽  
First Year ◽  
Early Diagnostics ◽  
Challenges And Opportunities

This review discusses early diagnostics and early intervention in developmental disorders in the light of brain development. The best instruments for early detection of cerebral palsy (CP) with or without intellectual disability are neonatal magnetic resonance imaging, general movements assessment at 2–4 months and from 2–4 months onwards, the Hammersmith Infant Neurological Examination and Standardized Infant NeuroDevelopmental Assessment. Early detection of autism spectrum disorders (ASD) is difficult; its first signs emerge at the end of the first year. Prediction with the Modified Checklist for Autism in Toddlers and Infant Toddler Checklist is possible to some extent and improves during the second year, especially in children at familial risk of ASD. Thus, prediction improves substantially when transient brain structures have been replaced by permanent circuitries. At around 3 months the cortical subplate has dissolved in primary motor and sensory cortices; around 12 months the cortical subplate in prefrontal and parieto-temporal cortices and cerebellar external granular layer have disappeared. This review stresses that families are pivotal in early intervention. It summarizes evidence on the effectiveness of early intervention in medically fragile neonates, infants at low to moderate risk, infants with or at high risk of CP and with or at high risk of ASD.

scholarly journals Health-Related Quality of Life in Children with Developmental Disorders

2021 ◽  
Author(s):  
Marina M. Schoemaker ◽  
Suzanne Houwen
Keyword(s):  
Quality Of Life ◽  
Developmental Disorders ◽  
Developmental Coordination Disorder ◽  
Autism Spectrum ◽  
Future Research ◽  
Health Related Quality ◽  
Related Quality ◽  
Health Related ◽  
Lower Hrqol

Abstract Purpose of Review (1) To give an overview of what is currently known about health-related quality of life (HRQoL) in three common and co-occurring developmental disorders: attention deficit hyperactivity disorder (ADHD), autism spectrum disorders (ASD), and developmental coordination disorder (DCD), and (2) to provide directions for future research. Recent Findings HRQoL is compromised in all three developmental disorders, affecting various domains of HRQoL. However, some domains are more affected than others depending on the nature of the core deficits of the disorder. Overall, parents’ rate HRQoL of their children lower than the children themselves. Children with ASD and ADHD with co-occurring disorders have lower HRQoL compared to those with singular disorders. Future studies in DCD are needed to investigate the effect of co-occurring disorder in this population. Summary Children with developmental disorders have lower HRQoL than typically developing children. Future research should focus on the effects of co-occurring disorders on HRQoL and on protective factors that may increase HRQoL. HRQoL should be a part of clinical assessment, as it reveals the areas in life children are struggling with that could be targeted during intervention.

AUTMINER: A SYSTEM FOR EXTRACTING ASD-RELATED GENES USING TEXT MINING

2011 ◽  
Vol 19 (01) ◽  
pp. 113-125 ◽  
Author(s):  
LEJUN GONG ◽  
XIAO SUN ◽  
DONGKE JIANG ◽  
SHENGTAO GONG
Keyword(s):  
Autism Spectrum Disorders ◽  
Text Mining ◽  
Genetic Screening ◽  
Gene Network ◽  
Developmental Disorders ◽  
Autism Spectrum ◽  
Major Focus ◽  
Genetic Complexity ◽  
Spectrum Disorders ◽  
Reference Tool

Autism spectrum disorders (ASD) represent a group of developmental disorders with strong genetic underpinnings. To explore the genetic complexity of ASD, we developed AutMiner (), a public web-portal for the collection of genes linked to ASD, and the implementation of an autism-centre network. AutMiner extracts candidate genes associated with ASD using text mining from 9276 abstracts. Compared to other recent systems, gene entries are richer to provide a reference for clinical geneticists. AutMiner also constructs ASD-related network consisting of autism-gene network and gene-gene network. To the best of our knowledge, this is the first web example of ASD-related network. The major focus of AutMiner is to offer a valuable reference tool for clinical geneticists in establishing and implementing effective genetic screening programmes for those patients with ASD.

Autism Spectrum and Other Developmental Disorders and ADHD

2017 ◽  
pp. 129-143
Author(s):  
Jennifer L. McLaren ◽  
Jonathan D. Lichtenstein ◽  
Sarah Y. Bessen ◽  
Fern Baldwin
Keyword(s):  
Developmental Disorders ◽  
Autism Spectrum

scholarly journals The Impact of MNRI Therapy on the Levels of Neurotransmitters Associated with Inflammatory Processes

2020 ◽  
Vol 21 (4) ◽  
pp. 1358 ◽  
Author(s):  
Tatiana V. Tatarinova ◽  
Trina Deiss ◽  
Lorri Franckle ◽  
Susan Beaven ◽  
Jeffrey Davis
Keyword(s):  
Attention Deficit ◽  
Attention Deficit Disorder ◽  
Emotional Regulation ◽  
Cognitive Skills ◽  
Developmental Disorders ◽  
Negative Impact ◽  
Autism Spectrum ◽  
Post Traumatic Stress ◽  
Compulsive Disorder ◽  
The Impact

The neurotransmitter levels of representatives from five different diagnosis groups were tested before and after participation in the MNRI®—Masgutova Neurosensorimotor Reflex Intervention. The purpose of this study was to ascertain neurological impact on (1) Developmental disorders, (2) Anxiety disorders/OCD (Obsessive Compulsive Disorder), PTSD (Post-Traumatic Stress disorder), (3) Palsy/Seizure disorders, (4) ADD/ADHD (Attention Deficit Disorder/Attention Deficit Disorder Hyperactive Disorder), and (5) ASD (Autism Spectrum Disorder) disorders. Each participant had a form of neurological dysregulation and typical symptoms respective to their diagnosis. These diagnoses have a severe negative impact on the quality of life, immunity, stress coping, cognitive skills, and social assimilation. This study showed a trend towards optimization and normalization of neurological and immunological functioning, thus supporting the claim that the MNRI method is an effective non-pharmacological neuromodulation treatment of neurological disorders. The effects of MNRI on inflammation have not yet been assessed. The resulting post-MNRI changes in participants’ neurotransmitters show significant adjustments in the regulation of the neurotransmitter resulting in being calmer, a decrease of hypervigilance, an increase in stress resilience, behavioral and emotional regulation improvements, a more positive emotional state, and greater control of cognitive processes. In this paper, we demonstrate that the MNRI approach is an intervention that reduces inflammation. It is also likely to reduce oxidative stress and encourage homeostasis of excitatory neurotransmitters. MNRI may facilitate neurodevelopment, build stress resiliency, neuroplasticity, and optimal learning opportunity. There have been no reported side effects of MNRI treatments.

scholarly journals Kinetic analysis of the action of Leiurus scorpion alpha-toxin on ionic currents in myelinated nerve.

1985 ◽  
Vol 86 (5) ◽  
pp. 739-762 ◽  
Author(s):  
G K Wang ◽  
G Strichartz
Keyword(s):  
Steady State ◽  
Ionic Currents ◽  
Na Channel ◽  
Dependent Manner ◽  
Na Current ◽  
Toxin Concentration ◽  
Toxin Molecule ◽  
Channel Inactivation ◽  
Na Currents ◽  
Voltage Dependent

The effects of a neurotoxin, purified from the venom of the scorpion Leiurus quinquestriatus, on the ionic currents of toad single myelinated fibers were studied under voltage-clamp conditions. Unlike previous investigations using crude scorpion venom, purified Leiurus toxin II alpha at high concentrations (200-400 nM) did not affect the K currents, nor did it reduce the peak Na current in the early stages of treatment. The activation of the Na channel was unaffected by the toxin, the activation time course remained unchanged, and the peak Na current vs. voltage relationship was not altered. In contrast, Na channel inactivation was considerably slowed and became incomplete. As a result, a steady state Na current was maintained during prolonged depolarizations of several seconds. These steady state Na currents had a different voltage dependence from peak Na currents and appeared to result from the opening of previously inactivated Na channels. The opening kinetics of the steady state current were exponential and had rates approximately 100-fold slower than the normal activation processes described for transitions from the resting state to the open state. In addition, the dependence of the peak Na current on the potential of preceding conditioning pulses was also dramatically altered by toxin treatment; this parameter reached a minimal value near a membrane potential of -50 mV and then increased continuously to a "plateau" value at potentials greater than +50 mV. The amplitude of this plateau was dependent on toxin concentration, reaching a maximum value equal to approximately 50% of the peak current; voltage-dependent reversal of the toxin's action limits the amplitude of the plateauing effect. The measured plateau effect was half-maximum at a toxin concentration of 12 nM, a value quite similar to the concentration producing half of the maximum slowing of Na channel inactivation. The results of Hill plots for these actions suggest that one toxin molecule binds to one Na channel. Thus, the binding of a single toxin molecule probably both produces the steady state currents and slows the Na channel inactivation. We propose that Leiurus toxin inhibits the conversion of the open state to inactivated states in a voltage-dependent manner, and thereby permits a fraction of the total Na permeability to remain at membrane potentials where inactivation is normally complete.

scholarly journals Preparation for Independent Life of People with ASD and Other Developmental Disorders in The Autonomous Noncommercial Organization «Adain Lo» (ANO «Adain Lo»).

2018 ◽  
Vol 16 (1) ◽  
pp. 29-35
Author(s):  
A.A. Ginsburg ◽  
M.E. Gitshabash ◽  
Ya.L. Ivanova
Keyword(s):  
Developmental Disorders ◽  
Autism Spectrum ◽  
Adults With Autism ◽  
Saint Petersburg ◽  
Independent Life ◽  
Spectrum Disorders ◽  
Self Service ◽  
Role Of Parents ◽  
Commercial Organization

The problems of preparation of children and adults with autism spectrum disorders and other developmental disabilities for independent life, modern ways of development of their independence are considered. The role of parents in this process and parent-specialist interaction are stressed. The techniques of tutor support, parents and other specialists are described. Presented techniques are realized in autonomous non-commercial organization «Adain Lo» (Saint-Petersburg) and aimed for maintenance of independent life, self-service, game, communication and education of people with special needs.

scholarly journals LA ACTUACION SANITARIA EN ATENCIÓN TEMPRANA PARA PERSONAS CON TRASTORNO DE ESPECTRO AUTISTA (TEA): UNA EXPERIENCIA EN ANDALUCÍA

2017 ◽  
Vol 7 (1) ◽  
pp. 463
Author(s):  
Mª Araceli Sánchez Raya
Keyword(s):  
Health Care ◽  
Autism Spectrum Disorders ◽  
Early Intervention ◽  
Early Detection ◽  
Functional Recovery ◽  
Developmental Disorders ◽  
Autism Spectrum ◽  
Theoretical Interest ◽  
Children With Asd ◽  
Spectrum Disorders

Abstract.It is undeniable the importance of early detection in all developmental disorders, in children with ASD as well, for an early intervention in children and their families. An early intervention is a very important predictor in their functional recovery. That, put together with the growing incidence and prevalence of this kind of disorders, makes of our study field a matter of an increasing scientific and theoretical interest. In the current paper we deal with earlydetection, evaluation and intervention in children between 0 and 6 years with autism spectrum disorders in andalusian health care system.Resumen.Es innegable la importancia que tiene la detección precoz de cualquier trastorno del desarrollo –y por ende del TEA- para la intervención temprana con los menores y sus familias. Una intervención temprana constituye un importante predictor en la recuperación funcional de estos menores, y esto unido a la creciente incidencia y prevalencia de estos trastornos, hace de nuestro objeto de estudio un tema creciente de gran interés científico y teórico. En la presente comunicación abordamos el circuito de detección, evaluación e intervención temprana en niñas y niños de 0 a 6 años con trastorno del espectro autista en la sanidad andaluza.

scholarly journals Predictors of Quality of Life Among an International Sample of Mothers of Children 12 and Under With Corpus Callosum Disorders

2020 ◽  
Vol 14 (1) ◽  
Author(s):  
Peggy Henninger ◽  
Donna M. L. Heretick
Keyword(s):  
Quality Of Life ◽  
Corpus Callosum ◽  
Pervasive Developmental Disorders ◽  
Developmental Disorders ◽  
Online Survey ◽  
Autism Spectrum ◽  
Double Abcx Model ◽  
Double Abcx ◽  
Abcx Model

Previous research supports application of the Double ABCX model of family adaptation of parents of children with autism spectrum disorder and other pervasive developmental disorders. This is the first study to consider processes of adaptation among parents of children with agenesis of the corpus callosum (ACC). Using a quantitative cross-sectional design, an international sample of 266 mothers of children, aged 12 or under, with ACC completed an online survey. Parental reports of stress, resources, coping, and sense of coherence were evaluated as predictors of four subdimensions of parental quality of life for 178 mothers. In general, findings support the Double ABCX model as a viable approach to understanding processes that are related to quality of life among this group of mothers.

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