title: Mesenchymal stem cells attenuate peripheral neuronal degeneration in spinocerebellar ataxia type 1 knockin mice.
abstract: Spinocerebellar ataxia type 1 (SCA1) is a devastating neurodegenerative disorder in which an abnormally expanded polyglutamine tract is inserted into causative ataxin-1 proteins. We have previously shown that SCA1 knockin (SCA1-KI) mice over 6 months of age exhibit a degeneration of motor neuron axons and their encasing myelin sheaths, as reported in SCA1 patients. We examined whether axon degeneration precedes myelin degeneration or vice versa in SCA1-KI mice and then attempted to mitigate motor neuron degeneration by intrathecally administering mesenchymal stem cells (MSCs). Temporal examination of the diameters of motor neuron axons and their myelin sheaths revealed a decrease in diameter of the axon but not of the myelin sheaths in SCA1-KI mice as early as 1 month of age, which suggests secondary degeneration of the myelin sheaths. We injected MSCs into the intrathecal space of SCA1-KI mice at 1 month of age, which resulted in a significant suppression of degeneration of both motor neuron axons and myelin sheaths, even 6 months after the MSC injection. Thus, MSCs effectively suppressed peripheral nervous system degeneration in SCA1-KI mice. It has not yet been clarified how clinically administered MSCs exhibit significant therapeutic effects in patients with SCA1. The morphological evidence presented in this current mouse study might explain the mechanisms that underlie the therapeutic effects of MSCs that are observed in patients with SCA1.
authors.affiliation: Department of Orthopedic Surgery, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors.forename: Tokue
authors.initials: T
authors.lastname: Mieda
authors.affiliation: Department of Neurophysiology and Neural Repair, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors.forename: Nana
authors.initials: N
authors.lastname: Suto
authors.affiliation: Department of Neurophysiology and Neural Repair, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Iizuka
authors.affiliation: Department of Neurophysiology and Neural Repair, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors.forename: Serina
authors.initials: S
authors.lastname: Matsuura
authors.affiliation: Department of Orthopedic Surgery, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors.forename: Haku
authors.initials: H
authors.lastname: Iizuka
authors.affiliation: Department of Orthopedic Surgery, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Takagishi
authors.affiliation: Department of Neurophysiology and Neural Repair, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Department of Neurophysiology and Neural Repair, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Hirai
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000067696:Ataxin-1 / Q000235:genetics / Q000378:metabolism; D064987:Cell- and Tissue-Based Therapy; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000235:genetics*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000502:physiology; D004676:Myelin Basic Protein / Q000378:metabolism; D009410:Nerve Degeneration / Q000209:etiology* / Q000601:surgery*; D013116:Spinal Cord / Q000473:pathology; D020754:Spinocerebellar Ataxias / Q000150:complications* / Q000235:genetics / Q000473:pathology; D013997:Time Factors
chemical_list: C000593749:ATXN1 protein, human; D000067696:Ataxin-1; D004676:Myelin Basic Protein; D049452:Green Fluorescent Proteins
keywords: MSC; SCA1; axon; myelin; spinal motor neuron