Improvement of cerebellar ataxic gait by injecting Cbln1 into the cerebellum of cbln1-null mice

Eri Takeuchi, Aya Ishida, Michisuke Yuzaki, Dai Yanagihara

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Patients and rodents with cerebellar damage display ataxic gaits characterized by impaired coordination of limb movements. Here, gait ataxia in mice with a null mutation of the gene for the cerebellin 1 precursor protein (cbln1-null mice) was investigated by kinematic analysis of hindlimb movements during locomotion. The Cbln1 protein is predominately produced and secreted from cerebellar granule cells. The cerebellum of cbln1-null mice is characterized by an 80% reduction in the number of parallel fiber-Purkinje cell synapses compared with wild-Type mice. Our analyses identified prominent differences in the temporal parameters of locomotion between cbln1-null and wild-Type mice. The cbln1-null mice displayed abnormal hindlimb movements that were characterized by excessive toe elevation during the swing phase, and by severe hyperflexion of the ankles and knees. When recombinant Cbln1 protein was injected into the cerebellum of cbln1-null mice, the step cycle and stance phase durations increased toward those of wild-Type mice, and the angular excursions of the knee during a cycle period showed a much closer agreement with those of wild-Type mice. These findings suggest that dysfunction of the parallel fiber-Purkinje cell synapses might underlie the impairment of hindlimb movements during locomotion in cbln1-null mice.

Original languageEnglish
Article number6184
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - 2018 Dec 1

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Gait Ataxia
Cerebellum
Locomotion
Hindlimb
Purkinje Cells
Synapses
Knee
Protein Precursors
Dyskinesias
Toes
Gait
Recombinant Proteins
Biomechanical Phenomena
Ankle
Rodentia
Extremities

ASJC Scopus subject areas

  • General

Cite this

Improvement of cerebellar ataxic gait by injecting Cbln1 into the cerebellum of cbln1-null mice. / Takeuchi, Eri; Ishida, Aya; Yuzaki, Michisuke; Yanagihara, Dai.

In: Scientific Reports, Vol. 8, No. 1, 6184, 01.12.2018.

Research output: Contribution to journalArticle

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