Reigning in Excitatory Signaling in CDKL5 Deficiency.

Reigning in Excitatory Signaling in CDKL5 Deficiency. Epilepsy Curr. 2019 Aug 28;:1535759719869919 Authors: Forcelli PA Abstract AMPA Receptor Dysregulation and Therapeutic Interventions in a Mouse Model of CDKL5 Deficiency Disorder Yennawar M, White RS, Jensen FE. J Neurosci. 2019;39(24):4814-4828. Pathogenic mutations in cyclin-dependent kinase-like 5 (CDKL5) result in CDKL5 deficiency disorder (CDD), a rare disease marked by early-life seizures, autistic behaviors, and intellectual disability. Although mouse models of CDD exhibit dendritic instability and alterations in synaptic scaffolding proteins, studies of glutamate receptor levels and function are limited. Here, we used a novel mouse model of CDD, the Cdkl5R59X knock-in mouse (R59X), to investigate changes in synaptic glutamate receptor subunits and functional consequences. Male mice were used for all experiments to avoid the confounding effects of X-inactivation that would be present in female heterozygous mice. We showed that adult male R59X mice recapitulated the behavioral outcomes observed in other mouse models of CDD, including social deficits and memory and learning impairments, and exhibited decreased latency to seizure upon pentylenetetrazol (PTZ) administration. Furthermore, we observed a specific increase in GluA2-lacking AMPA receptors (AMPARs) in the adultR59X hippocampus, which is accompanied electrophysiologically by increased rectification ratio of AMPAR excitatory postsynaptic cu...
Source: Epilepsy Currents - Category: Neurology Tags: Epilepsy Curr Source Type: research

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Publication date: Available online 20 October 2019Source: Neurotoxicology and TeratologyAuthor(s): Rodrigo Moreno Klein, Camila Rigobello, Camila Borecki Vidigal, Kawane Fabrício Moura, Décio Sabbatini Barbosa, Daniela Cristina Ceccatto Gerardin, Graziela Scalianti Ceravolo, Estefânia Gastaldello MoreiraAbstractParacetamol (PAR) is an over-the-counter medicine used as analgesic or antipyretic by 40–50% of the pregnant women in different countries. Epidemiologic studies have been associating maternal use of PAR with neurodevelopmental disruption and special attention has been given to its potential...
Source: Neurotoxicology and Teratology - Category: Toxicology Source Type: research
In the general population, there is a strong association between having a seizure disorder and excess mortality. Waddy and colleagues examined epilepsy and seizures in a national end-stage kidney disease (ESKD) database. They found that having a diagnosis of epilepsy or seizures was 9-fold and 2-fold higher in patients with ESKD than in the general population. After adjusting for potential confounding variables, patients with ESKD and epilepsy or seizures were found to have an 11% and 14% increase in death compared with those patients with ESKD without either diagnosis.
Source: Kidney International - Category: Urology & Nephrology Tags: In This Issue Source Type: research
Patients with end-stage renal disease requiring dialysis and persons with epilepsy are at increased risk of death. However, there is little information related to the risk of death when the 2 conditions co-exist. In this issue, Waddy et  al. determined that among patients with end-stage renal disease, those with a diagnose of epilepsy or seizures have a higher risk of all-cause mortality compared with those who do not have an epilepsy or seizure diagnosis. This association was further modified by neurology consultation, with a low er risk in persons who had received a consultation.
Source: Kidney International - Category: Urology & Nephrology Authors: Tags: Commentary Source Type: research
AbstractFremanezumab (fremanezumab-vfrm; Ajovy®), a monoclonal antibody that targets calcitonin gene-related peptide (CGRP), is indicated for the prevention of migraine in adults in the EU and USA. Subcutaneous fremanezumab 225  mg once monthly or 675 mg once every 3 months was effective in reducing monthly migraine days or headache days in patients with episodic or chronic migraine in pivotal, 12-week clinical trials. Both regimens also reduce acute headache medication use and headache-related disability. Improvements were maintained through ≤ 52 weeks of additional treatment in a longer-...
Source: Drugs and Therapy Perspectives - Category: Drugs & Pharmacology Source Type: research
Objective: To compare the rate of malreduction after high fibular fractures associated with syndesmosis injury treated with open reduction and internal fixation, with either 2 screws or 1 knotless TightRope device. Design: Prospective randomized controlled multicenter trial. Setting: Eleven academic and community hospitals including Level 1 and Level 2 trauma centers across Canada. Patients/Participants: One hundred three patients with OTA/AO 44-C injuries with demonstrated radiographic syndesmosis diastasis or instability after malleolar bony fixation were followed for 12 months after treatment. Methods: Ope...
Source: Journal of Orthopaedic Trauma - Category: Orthopaedics Tags: Original Article Source Type: research
Conclusions: Three thousand eight hundred ten articles were identified, and 12 met inclusion criteria. These studies encompassed 497 patients with an average age of 14.1 years (8–18 years, range). Both operative and nonoperative management of displaced midshaft clavicle fractures in this population provide excellent rates of union and patient-reported outcome measures. Compared with nonoperative management, operative management yielded faster return to activity, superior Constant scores, and equal QuickDASH scores. Operative management had higher complication rates and complications that required secondary operativ...
Source: Journal of Orthopaedic Trauma - Category: Orthopaedics Tags: Review Article Source Type: research
ConclusionsWe conclude that mechanisms driving OA (which is defined as ‘impaired visually guided movement’) may underpin severe motor impairment, in autism. CVIS and VMIS may be useful indicators of severity of spatial cognitive impairment.
Source: Research in Autism Spectrum Disorders - Category: Psychiatry Source Type: research
Ring chromosome 14 syndrome is a rare chromosomal disorder characterized by early onset refractory epilepsy, intellectual disability, autism spectrum disorder and a number of diverse health issues.
Source: Orphanet Journal of Rare Diseases - Category: Internal Medicine Authors: Source Type: research
Conclusions: Our study showed a prevalence of ASD of 40.5 %, confirming the higher risk for this disorder in patients with TSC. However, the severity seems to have a notable variability in TSC patients. Risk factors for ASD are epilepsy, infantile spams, and mutations in TSC2.
Source: Orphanet Journal of Rare Diseases - Category: Internal Medicine Authors: Source Type: research
Abstract Whole-exome sequencing (WES) has revolutionized gene discovery in human disease, drastically improving detection of pathogenic variation, expanding the delineation of molecular networks, enriching characterization of genomic architecture and refining the genotype–endophenotype distinctions in heterogeneous phenotypes. WES studies, often aided by collaborative consortia, have proven particularly effective in identifying the genetic etiology of autism, epilepsy, neurodevelopmental disabilities, brain malformations, congenital heart disease, congenital diaphragmatic hernia, multiple congenital anomalie...
Source: Current Genetic Medicine Reports - Category: Genetics & Stem Cells Source Type: research
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