Zonisamide promotes survival of human-induced pluripotent stem cell-derived dopaminergic neurons in the striatum of female rats.

Parkinson's disease RRID:AB_2169021 RRID:AB_2190153 RRID:AB_2201528 RRID:AB_2244867 RRID:AB_2294104 RRID:AB_2340866 RRID:AB_2534074 RRID:AB_2534102 RRID:AB_2534105 RRID:AB_2535795 RRID:AB_2535864 RRID:AB_2556542 RRID:AB_2556546 RRID:AB_2556547 RRID:AB_2716768 RRID:AB_2801320 RRID:AB_390204 RRID:AB_442102 RRID:AB_477010 RRID:AB_90755 RRID:AB_94090 RRID:CVCL_RL23 RRID:RGD_1547866 RRID:RGD_9685748 RRID:SCR_001456 RRID:SCR_002798 RRID:SCR_010972 RRID:SCR_016264 RRID:SCR_017202 RRID:SCR_017205 RRID:SCR_017206 Zonisamide dopaminergic neuron induced pluripotent stem cell transplantation

Journal

Journal of neuroscience research
ISSN: 1097-4547
Titre abrégé: J Neurosci Res
Pays: United States
ID NLM: 7600111

Informations de publication

Date de publication:
08 2020
Historique:
received: 23 08 2019
revised: 15 05 2020
accepted: 17 05 2020
pubmed: 9 6 2020
medline: 24 8 2021
entrez: 8 6 2020
Statut: ppublish

Résumé

The transplantation of dopaminergic (DA) progenitors derived from pluripotent stem cells improves the behavior of Parkinson's disease model animals. However, the survival of DA progenitors is low, and the final yield of DA neurons is only approximately 0.3%-2% the number of transplanted cells. Zonisamide (ZNS) increases the number of survived DA neurons upon the transplantation of mouse-induced pluripotent stem (iPS) cell-derived DA progenitors in the rat striatum. In this study, we induced DA progenitors from human iPS cells and transplanted them into the striatum of female rats with daily administration of ZNS. The number of survived DA neurons was evaluated 1 and 4 months after transplantation by immunohistochemistry, which revealed that the number of survived DA neurons was significantly increased with the administration of ZNS. To assess the mechanism of action of ZNS, we performed a gene expression analysis to compare the gene expression profiles in striatum treated with or without ZNS. The analysis revealed that the expression of SLIT-and NTRK-like protein 6 (SLITRK6) was upregulated in rat striatum treated with ZNS. In conclusion, ZNS promotes the survival of DA neurons after the transplantation of human-iPS cell-derived DA progenitors in the rat striatum. SLITRK6 is suggested to be involved in this supportive effect of ZNS by modulating the environment of the host brain.

Identifiants

pubmed: 32506530
doi: 10.1002/jnr.24668
pmc: PMC7497107
doi:

Substances chimiques

Membrane Proteins 0
Slitrk6 protein, human 0
Zonisamide 459384H98V

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1575-1587

Informations de copyright

© 2020 Wiley Periodicals, Inc.

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Auteurs

Yoshifumi Miyawaki (Y)

Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan.

Bumpei Samata (B)

Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan.

Tetsuhiro Kikuchi (T)

Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan.

Kaneyasu Nishimura (K)

Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan.

Jun Takahashi (J)

Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan.

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