Potassium channel dysfunction in human neuronal models of Angelman syndrome
Disruptions in the ubiquitin protein ligase E3A (UBE3A) gene cause Angelman syndrome (AS). Whereas AS model mice have associated synaptic dysfunction and altered plasticity with abnormal behavior, whether similar or other mechanisms contribute to network hyperactivity and epilepsy susceptibility in AS patients remains unclear. Using human neurons and brain organoids, we demonstrate that UBE3A suppresses neuronal hyperexcitability via ubiquitin-mediated degradation of calcium- and voltage-dependent big potassium (BK) channels. We provide evidence that augmented BK channel activity manifests as increased intrinsic excitability in individual neurons and subsequent network synchronization. BK antagonists normalized neuronal excitability in both human and mouse neurons and ameliorated seizure susceptibility in an AS mouse model. Our findings suggest that BK channelopathy underlies epilepsy in AS and support the use of human cells to model human developmental diseases.
The objective of this study was to develop an in-situ gel containing lorazepam (LZM) loaded nanostructured lipid carriers (NLCs) for direct nose-to-brain delivery in order to increase drug therapeutic efficacy in the treatment of epilepsy. Accordingly, LZM loaded NLCs were formulated using emulsification solvent diffusion and evaporation method; then the effects of the formulation variables on different physicochemical characteristics of NLCs were investigated. Thermosensitive in-situ gels containing LZM-NLCs were prepared using a combination of chitosan and β-glycerol phosphate (β-GP). The anticonvulsant efficac...
Publication date: 15 August 2020Source: Journal of Alloys and Compounds, Volume 832Author(s): Mohammad Nouri-Felekori, Mehrdad Khakbiz, Nader Nezafati, Javad Mohammadi, Mohamadreza Baghaban Eslaminejad, Nesa Fani
Charlotte Figi, a child with a catastrophic type of epilepsy who went on to inspire a CBD movement, has passed away at age 13. CNN's Dr. Sanjay Gupta reflects on her life.
Publication date: June 2020Source: Epilepsy &Behavior, Volume 107Author(s): María Puig-Molto, Emilio Pol-Yanguas, Lidia Segarra, Blanca Lumbreras
Conclusion: Our current study will provide important imaging-derived data that may add relevance to the clinically derived outcomes from liraglutide effect and action in diabetes: evaluation of cardiovascular outcome results and semaglutide and cardiovascular outcomes in patients with type 2 diabetic mellitus 6 trials.
Authors: Li R, He M, Wu B, Zhang P, Zhang Q, Chen Y Abstract α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are the predominant mediators of glutamate-induced excitatory neurotransmission. It is widely accepted that AMPA receptors are critical for the generation and spread of epileptic seizure activity. Dysfunction of AMPA receptors as a causal factor in patients with intractable epilepsy results in neurotransmission failure. Brain-specific serine/threonine-protein kinase 1 (SAD-B), a serine-threonine kinase specifically expressed in the brain, has been shown to regulate AMPA receptor-m...
Conditions: Pancreatic Adenosquamous Carcinoma; Resectable Pancreatic Adenocarcinoma; Pancreatic Cancer Interventions: Drug: Oxaliplatin; Drug: Irinotecan Hydrochloride; Drug: Leucovorin Calcium; Drug: Fluorouracil; Procedure: Resection; Other: Questionnaire Administration Sponsors: Alliance for Clinical Trials in Oncology; National Cancer Institute (NCI) Not yet recruiting
ConclusionClinical work ‐up of an individual with developmental delay, hyperactivity, anxiety, and an uncharacteristically happy demeanor should prompt methylation studies to rule out mAS. We expand the phenotypic spectrum of AS to include features that overlap with Prader‐Willi such as hyperphagia.
This article also addresses the neuropharmacological potential of taurine analogs.Graphical abstract
Nature Reviews Neurology 12, 584 (2016). doi:10.1038/nrneurol.2016.133 Authors: Karin Buiting, Charles Williams &Bernhard Horsthemke Angelman syndrome is a rare neurogenetic disorder that is characterized by microcephaly, severe intellectual deficit, speech impairment, epilepsy, EEG abnormalities, ataxic movements, tongue protrusion, paroxysms of laughter, abnormal sleep patterns, and hyperactivity. Angelman syndrome results from loss of function of the imprinted UBE3A (ubiquitin–protein