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标题：Improvement of cerebellar ataxic gait by injecting Cbln1 into the cerebellum of cbln1-null mice
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作者：Eri Takeuchi ; Aya Ito-Ishida ; Michisuke Yuzaki 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2018
卷号：8
期号：1
页码：6184
DOI：10.1038/s41598-018-24490-0
语种：English
出版社：Springer Nature
摘要：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.