Introducing treatment strategy for cerebellar ataxia in mutant med mice: combination of acetazolamide and 4-aminopyridine.
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.
['Abbasi|Samira|S|', 'Abbasi|Ataollah|A|', 'Sarbaz|Yashar|Y|']
D015761:4-Aminopyridine D000086:Acetazolamide D000200:Action Potentials D000818:Animals D002524:Cerebellar Ataxia D004195:Disease Models, Animal D004359:Drug Therapy, Combination D051379:Mice D008817:Mice, Mutant Strains D018696:Neuroprotective Agents D011689:Purkinje Cells
Ataxia Ion channels Modeling Neuroprotective agents Therapeutics