title: Introducing treatment strategy for cerebellar ataxia in mutant med mice: combination of acetazolamide and 4-aminopyridine.
abstract: Purkinje neurons are the sole output neuron of the cerebellar cortex, and they generate high-frequency action potentials. Electrophysiological dysfunction of Purkinje neurons causes cerebellar ataxia. Mutant med mice have the lack of expression of the Scn8a gene. This gene encodes the NaV1.6 protein. In med Purkinje neurons, regular high-frequency firing is slowed, and med mice are ataxic. The aim of this study was to propose the neuroprotective drugs which could be useful for ataxia treatment in med mice, and to investigate the neuroprotective effects of these drugs by simulation. Simulation results showed that Kv4 channel inhibitors and BK channel activators restored the normal electrophysiological properties of the med Purkinje neurons. 4-Aminopyridine (4-AP) and acetazolamide (ACTZ) were proposed as neuroprotective drugs for Kv4 channel inhibitor and BK channel activator, respectively.
authors: Computational Neuroscience Laboratory, Department of Biomedical Engineering, Faculty of Electrical Engineering, Sahand University of Technology, Tabriz, Iran.
authors: Samira
authors: S
authors: Abbasi
authors: Computational Neuroscience Laboratory, Department of Biomedical Engineering, Faculty of Electrical Engineering, Sahand University of Technology, Tabriz, Iran. Electronic address: ata.abbasi@sut.ac.ir.
authors: Ataollah
authors: A
authors: Abbasi
authors: School of Engineering-Emerging Technologies, University of Tabriz, Tabriz, Iran.
authors: Yashar
authors: Y
authors: Sarbaz
mesh_terms: D015761:4-Aminopyridine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000086:Acetazolamide / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002524:Cerebellar Ataxia / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D051379:Mice; D008817:Mice, Mutant Strains; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D011689:Purkinje Cells / Q000187:drug effects
chemical_list: D018696:Neuroprotective Agents; D015761:4-Aminopyridine; D000086:Acetazolamide
keywords: Ataxia; Ion channels; Modeling; Neuroprotective agents; Therapeutics