scholarly journals Enhancing glucose metabolism via gluconeogenesis is therapeutic in a zebrafish model of Dravet syndrome

2021 ◽  
Author(s):  
Rajeswari Banerji ◽  
Christopher Huynh ◽  
Francisco Figueroa ◽  
Matthew T Dinday ◽  
Scott C Baraban ◽  
...  
Keyword(s):  
Neurodevelopmental Disorders ◽  
Translocator Protein ◽  
Dravet Syndrome ◽  
Pediatric Epilepsy ◽  
Zebrafish Model ◽  
Glucose Levels ◽  
Metabolic Defects ◽  
Library Screen ◽  
Electrographic Seizures ◽  
And Behavior

Abstract Energy producing pathways are novel therapeutic targets for the treatment of neurodevelopmental disorders. Here, we focused on correcting metabolic defects in a catastrophic pediatric epilepsy, Dravet syndrome which is caused by mutations in sodium channel NaV1.1 gene, SCN1A. We utilized a translatable zebrafish model of Dravet syndrome (scn1lab) which exhibits key characteristics of Dravet syndrome patients and shows metabolic deficits accompanied by downregulation of gluconeogenesis genes, pck1 and pck2. Using a metabolism-based small library screen, we identified compounds that increased gluconeogenesis via upregulation of pck1 gene expression in scn1lab larvae. Treatment with PK11195, a pck1 activator and a translocator protein ligand, normalized dysregulated glucose levels, metabolic deficits, translocator protein expression and significantly decreased electrographic seizures in mutant larvae. Inhibition of pck1 in wild-type larvae mimicked metabolic and behavior defects observed in scn1lab mutants. Together, this suggests correcting dysregulated metabolic pathways can be therapeutic in neurodevelopmental disorders such as Dravet syndrome arising from ion channel dysfunction.

Play Therapy for Children With Neurodevelopmental Disorders

2019 ◽  
pp. 264-280
Author(s):  
Gaurav Thapliyal ◽  
Sushma Kotnala
Keyword(s):  
Play Therapy ◽  
Neurodevelopmental Disorders ◽  
Therapeutic Approaches ◽  
The World ◽  
Recent Trends ◽  
And Behavior

A play is referred to the language of children through which they express and communicate their feelings, thoughts, and behavior in a playful way. Play therapy enables children to gain an understanding of themselves and the world around them and helps them to overcome behavioral, emotional, social, and various other issues through play activities. The chapter majorly focuses on the effectiveness of play therapy in different neurodevelopmental disorders. Recent trends and studies suggested that play therapy is one of the most favored therapeutic approaches used in the children with various neurodevelopmental disorders.

Yoga Therapy on Cognitive Function in Neurodevelopmental Disorders

2020 ◽  
pp. 143-160
Author(s):  
Artchoudane Soccalingam ◽  
Meena Ramanathan ◽  
Ananda Balayogi Bhavanani
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cognitive Function ◽  
Neurodevelopmental Disorders ◽  
Body Awareness ◽  
Yoga Therapy ◽  
Breath Awareness ◽  
Major Factors ◽  
Sensory Processes ◽  
And Behavior

Neurodevelopmental disorders (NDDs) are birth imperfections that cause dysfunction in cognitive and sensory processes and impairment in motor function, communication, and behavior. The major factors responsible for increasing incidence of NDDs are genetic, psychosocial, and excessive use of drugs. Yoga alleviates neurological problems and NDDs. Asana is a physical movement with breath awareness that facilitates the development of body awareness, concentration, and memory and provides vital energy for children with neurodevelopmental disability. Yoga therapy improves sensory coordination and motor imitations that enable persons with cognitive disabilities to make meaningful response by the integration of senses and functions of central nervous system.

At-Risk Driving Behavior in Drivers with Diabetes: A Neuroergonomics Approach

2017 ◽  
Vol 61 (1) ◽  
pp. 1881-1885
Author(s):  
Jennifer Merickel ◽  
Robin High ◽  
Lynette Smith ◽  
Chris Wichman ◽  
Emily Frankel ◽  
...  
Keyword(s):  
At Risk ◽  
Real World ◽  
Driver Behavior ◽  
Wearable Sensors ◽  
Sensor Data ◽  
Continuous Glucose Monitor ◽  
Glucose Levels ◽  
Driver Performance ◽  
Safety Interventions ◽  
And Behavior

This pilot study tackles the overarching need for driver-state detection through real-world measurements of driver behavior and physiology in at-risk drivers with type 1 diabetes mellitus (DM). 35 drivers (19 DM, 14 comparison) participated. Real-time glucose levels were measured over four weeks with continuous glucose monitor (CGM) wearable sensors. Contemporaneous real-world driving performance and behavior were measured with in-vehicle video and electronic sensor instrumentation packages. Results showed clear links between at-risk glucose levels (particularly hypoglycemia) and changes in driver performance and behavior. DM participants often drove during at-risk glucose levels (low and high) and showed cognitive impairments in key domains for driving, which are likely linked to frequent hypoglycemia. The finding of increased driving risk in DM participants was mirrored in state records of crashes and traffic citations. Combining sensor data and phenotypes of driver behavior can inform patients, caregivers, safety interventions, policy, and design of supportive in-vehicle technology that is responsive to driver state.

scholarly journals Autistic Spectrum Disorder in the Context of Pandemic by Covid-19: Caring for Children and Caregivers

2021 ◽  
Author(s):  
José Vilelas
Keyword(s):  
Autism Spectrum Disorder ◽  
Neurodevelopmental Disorders ◽  
Scientific Evidence ◽  
Children With Autism ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Special Importance ◽  
Negative Behaviors ◽  
The Family ◽  
And Behavior

The COVID-19 pandemic has brought important challenges to society and families, with repercussions on child behavior and development with special importance for children with neurodevelopmental disorders that affect and impair the child’s functionality: Autism spectrum disorder. Thus, we set as objective to Identify and analyze the scientific evidence of interventions performed on children with Autism Spectrum Disorder in the context of a Covid-19 pandemic. A search was conducted in the MEDLINE, PubMed, CINHAL databases and gray literature. Children with Autism Spectrum Disorders (EAP) may become more anxious, agitated and unregulated with the change in routines to which they are subjected in this phase of the Covid 19 pandemic. Autism disorders affect communication, social interaction and behavior, usually with a tendency to be repetitive and routine, but in a scenario of pandemic and social isolation, anxiety and agitation may be more pronounced and, in more severe cases, there may be less capacity to function. It is important that the family of the child with ASD propose cooperative activities or resources that they have at home and that can be adapted. The insertion of some tasks contributes to the establishment of the ability to play independently. In it, the child gets involved independently. And so it prevents negative behaviors from occurring due to leisure and the need for attention, also favoring concentration.

scholarly journals Role of matrix metalloproteinase-9 in neurodevelopmental disorders and plasticity in Xenopus tadpoles

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Sayali V Gore ◽  
Eric J James ◽  
Lin-chien Huang ◽  
Jenn J Park ◽  
Andrea Berghella ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Neurodevelopmental Disorders ◽  
Neuronal Development ◽  
Neural Circuit ◽  
Critical Role ◽  
Matrix Metalloproteinase 9 ◽  
Abnormal Development ◽  
Synaptic Connectivity ◽  
And Behavior ◽  
Metalloproteinase 9

Matrix metalloproteinase-9 (MMP-9) is a secreted endopeptidase targeting extracellular matrix proteins, creating permissive environments for neuronal development and plasticity. Developmental dysregulation of MMP-9 may also lead to neurodevelopmental disorders (ND). Here we test the hypothesis that chronically elevated MMP-9 activity during early neurodevelopment is responsible for neural circuit hyperconnectivity observed in Xenopus tadpoles after early exposure to valproic acid (VPA), a known teratogen associated with ND in humans. In Xenopus tadpoles, VPA exposure results in excess local synaptic connectivity, disrupted social behavior and increased seizure susceptibility. We found that overexpressing MMP-9 in the brain copies effects of VPA on synaptic connectivity, and blocking MMP-9 activity pharmacologically or genetically reverses effects of VPA on physiology and behavior. We further show that during normal neurodevelopment MMP-9 levels are tightly regulated by neuronal activity and required for structural plasticity. These studies show a critical role for MMP-9 in both normal and abnormal development.

scholarly journals Cannabis Treatment in Children with Epilepsy: Practices of Canadian Neurologists

2020 ◽  
Vol 47 (4) ◽  
pp. 511-518 ◽  
Author(s):  
Stephanie M. DeGasperis ◽  
Richard Webster ◽  
Daniela Pohl
Keyword(s):  
Online Survey ◽  
Focal Epilepsy ◽  
Poor Quality ◽  
Dravet Syndrome ◽  
Pediatric Epilepsy ◽  
Medical Cannabis ◽  
Idiopathic Generalized Epilepsy ◽  
Community Based ◽  
Drug Resistant Epilepsy ◽  
Generalized Epilepsy

ABSTRACT:Background:Medical cannabis has recently emerged as a treatment option for children with drug-resistant epilepsy. Despite the fact that many pediatric epilepsy patients across Canada are currently being treated with cannabis, little is known about the attitudes of neurologists toward cannabinoid treatment of children with epilepsy.Methods:A 21-item online survey was distributed via email to 148 pediatric neurologists working in hospitals and community clinics across Canada. Questions were related to clinical practice and demographics.Results:This survey achieved a response rate of 38% (56 Canadian neurologists). These neurologists were treating 668 pediatric epilepsy patients with cannabinoids. While 29% of neurologists did not support cannabis treatment in their patients, 34% prescribed cannabis, and 38% referred to another authorizing physician, mostly to community-based non-neurologists. The majority of neurologists considered cannabis for patients with Dravet syndrome (68%) and Lennox–Gastaut syndrome (64%) after an average of three failed anticonvulsants. Twenty-seven percent considered it for patients with idiopathic generalized epilepsy, and 18% for focal epilepsy. No neurologist used cannabis as a first-line treatment. All neurologists had at least one hesitation regarding cannabis treatment in pediatric epilepsy. The most common one was poor evidence (66%), followed by poor quality control (52%) and high cost (50%).Conclusions:The majority of Canadian pediatric neurologists consider using cannabis as a treatment for epilepsy in children. With many gaps in evidence and high patient-driven demand for cannabis therapy, this survey provides immediate information from the “wisdom of the crowd,” to aid neurologists until further evidence is available.

Abstract 592: Nutrigenomic Screening of Functional Foods Regulating Gluconeogenesis: A Zebrafish Pilot Study

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Ji Dong Bai ◽  
Youdong Wang ◽  
Xiao-Yan Wen
Keyword(s):  
Gene Expression ◽  
Side Effects ◽  
Functional Food ◽  
Functional Foods ◽  
Fruits And Vegetables ◽  
Zebrafish Model ◽  
Fluorescent Reporter ◽  
Reporter Line ◽  
Glucose Levels

Introduction/rationale: Current anti-diabetic drug treatments have a variety of adverse side effects. Identifying functional foods with anti-diabetic properties may be the key to preventing and managing T2DM while minimizing side effects. Studies found that Pck-1 gene is often down-regulated by anti-diabetic drugs, as its enzyme is responsible for catalyzing the rate-limiting step of gluconeogenesis. In our study, we screened for functional foods that can down-regulate the expression of the Pck-1 gene. The newly emerged zebrafish (Danio rerio) is aptly suited for in vivo nutrigenomic screening due to its large clutch size and conservation of molecular pathways with humans, including those involved in glucose regulation. Methods: We exposed zebrafish larve (Tg(Pck-1:luc), a luminescent reporter line for Pck-1), at 4 days post fertilization (dpf) to extracts from forty functional fruits and vegetables. The level of Pck-1 expression was quantified by luminescence at 6 dpf. Extracts which resulted in a lower reading of luminescence were interpreted as functional foods that could successfully down-regulate Pck-1 expression, and therefore may be potential therapeutic for T2DM. We further validated our results using a fluorescent reporter line for Pck-1 (Pck-1:eGFP). Results: We completed toxicity assays on the functional food extracts to determine the optimal concentrations and conditions for nutrigenomic screening. Preliminary results show that bamboo and cherry extracts significantly reduced Pck-1 gene expression by two fold (p<0.05). Other functional food extracts, such as grape, cucumber, cabbage, spinach, flat beans, and lemon also reduced Pck-1 gene expression. Interestingly, garlic extracts increased Pck-1 gene expression. Conclusion and Discussion: We identified two functional food extracts that successfully reduced Pck-1 expression in zebrafish models. Increasing the intake of these two functional foods may regulate blood glucose levels in T2DM patients. Further research elucidating the active ingredient in these foods is required. The Pck-1 zebrafish model can be employed for further nutrigenomic screening and/or for drug discovery purposes.

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