Abstract: Impaired axonal transport has been observed in patients with amyotrophic lateral sclerosis (ALS) and in animal models, suggesting that transport proteins likely play a critical role in the pathological mechanism of ALS. Dysregulation of Kinesin-family-member 5α (Kif5α), a neuron-specific isoform of heavy chain kinesin family, has been described in several neurological disorders, in humans and animal models, including ALS. In this study, we determined Kif5α expression by gene sequencing, quantitative reverse transcription-polymerase chain reaction, and western blot assay in the cervical spinal cord of wobbler mice and immunofluorescence staining in dissociated cultures of the ventral horn. Further, we observed the distribution of Kif5α and mitochondria along motor neuronal branches by confocal imaging. Our results showed that Kif5α expression was greatly dysregulated in wobbler mice, which resulted in altered distribution of Kif5α along motor neuronal branches with an abnormal mitochondrial distribution. Thus, our results indicate that dysregulation of Kif5 and therefore abnormal transport in motor neuronal branches in this ALS model could be causative for several pathological findings at the cellular level, like misallocation of cytoskeletal proteins or organelles like mitochondria.

Key words: amyotrophic lateral sclerosis, cell culture, kinesin, mitochondria, neurodegeneration, spinal cord, transport