Altered nicotinamide adenine dinucleotide (NADH) fluorescence in dtsz mutant hamsters reflects differences in striatal metabolism between severe and mild dystonia

Abstract

The dt(sz) mutant hamster represents a unique rodent model of idiopathic paroxysmal dystonia. Previous data, collected post-mortem or in anesthetized hamsters under basal conditions, indicated the critical involvement of enhanced striatal neuronal activity. To assess the importance of an enhanced striatal neuronal activity directly during a dystonic episode, continuous monitoring of changes in brain metabolism and therefore neuronal activity indirectly in awake, freely moving animals is necessary. Determination of CNS metabolism by NADH measurement by laser-induced fluorescence spectroscopy in conscious dt(sz) and nondystonic control hamsters revealed reversible decreased NADH fluorescence during dystonic episodes. The degree of change corresponded to the severity of dystonia. This study represents the first application of this innovative method in freely moving animals exhibiting a movement disorder. Our data clearly confirm that the expression of paroxysmal dystonia in dt(sz) mutant hamsters is associated with enhanced striatal neuronal activity and further underscore the versatile application of NADH fluorescence measurements in neuroscience.