Motor coordination and spatial orientation are affected by neurofilament maldistribution: correlations with regional brain activity of cytochrome oxidase.

Abstract

NFH-LacZ transgenic mice are characterized by an early accumulation of the neurofilament cytoskeleton in the cell bodies of neurons with age-associated abnormalities of motor neurons and cerebellar Purkinje cells. In comparison to normal littermate controls, irrespective of age (3 and 12-20 months), NFH-LacZ transgenic mice had a lower number of rears in an open field, deficiencies in some motor-coordination tests, and a higher number of quadrant entries and escape latencies while swimming toward a visible platform. Decreased cytochrome oxidase activity in the lateral reticular nucleus of NFH-LacZ mice was associated with poor performance in two motor coordination tests. Lower metabolic activity in the lateral reticular nucleus may be secondary to previously described cerebellar abnormalities, leading to deficient motor control. The dramatic cytoskeletal perturbation characterizing NFH-LacZ mice affects only selective neuronal populations and results in selective behavioral deficits, which can be correlated with regional brain metabolic activity.