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Electric signals regulate directional migration of ventral midbrain derived dopaminergic neural progenitor cells via Wnt/GSK3β signaling.
Exp Neurol 2015; 263:113-21EN

Abstract

Neural progenitor cell (NPC) replacement therapy is a promising treatment for neurodegenerative disorders including Parkinson's disease (PD). It requires a controlled directional migration and integration of NPCs, for example dopaminergic (DA) progenitor cells, into the damaged host brain tissue. There is, however, only limited understanding of how to regulate the directed migration of NPCs to the diseased or damaged brain tissues for repair and regeneration. The aims of this study are to explore the possibility of using a physiological level of electrical stimulation to regulate the directed migration of ventral midbrain NPCs (NPCs(vm)), and to investigate their potential regulation via GSK3β and associated downstream effectors. We tested the effects of direct-current (DC) electric fields (EFs) on the migration behavior of the NPCs(vm). A DC EF induced directional cell migration toward the cathode, namely electrotaxis. Reversal of the EF polarity triggered a sharp reversal of the NPC(vm) electrotaxis. The electrotactic response was both time and EF voltage dependent. Pharmacologically inhibiting the canonical Wnt/GSK3β pathway significantly reduced the electrotactic response of NPCs(vm), which is associated with the down-regulation of GSK3β phosphorylation, β-catenin activation and CLASP2 expression. This was further proved by RNA interference of GSK3β, which also showed a significantly reduced electrotactic response in association with reduced β-catenin activation and CLASP2 expression. In comparison, RNA interference of β-catenin slightly reduced electrotactic response and CLASP2 expression. Both pharmacological inhibition of Wnt/GSK3β and RNA interference of GSK3β/β-catenin clearly reduced the asymmetric redistribution of CLASP2 and its co-localization with α-tubulin. These results suggest that Wnt/GSK3β signaling contributes to the electrotactic response of NPCs(vm) through the coordination of GSK3β phosphorylation, β-catenin activation, CLASP2 expression and asymmetric redistribution to the leading edge of the migrating cells.

Authors+Show Affiliations

Laboratory Animal Center, China Medical University, Shenyang, 110001, China; School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Cardiff CF14 4XY, UK.School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Cardiff CF14 4XY, UK.School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Cardiff CF14 4XY, UK.Institute of Neurosciences, Fourth Military Medical University, 169 West Changle Road, Xi'an 710032, China.Bio-X Center, School of Life Science and Technology, Harbin Institute of Technology, Harbin 150080, China.Institute of Neurosciences, Fourth Military Medical University, 169 West Changle Road, Xi'an 710032, China.School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Cardiff CF14 4XY, UK.School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Cardiff CF14 4XY, UK; Department of Dermatology, China Medical University, Shenyang, 110001, China. Electronic address: SongB3@cardiff.ac.uk.

Pub Type(s)

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

Language

eng

PubMed ID

25265211

Citation

Liu, Jia, et al. "Electric Signals Regulate Directional Migration of Ventral Midbrain Derived Dopaminergic Neural Progenitor Cells Via Wnt/GSK3β Signaling." Experimental Neurology, vol. 263, 2015, pp. 113-21.
Liu J, Zhu B, Zhang G, et al. Electric signals regulate directional migration of ventral midbrain derived dopaminergic neural progenitor cells via Wnt/GSK3β signaling. Exp Neurol. 2015;263:113-21.
Liu, J., Zhu, B., Zhang, G., Wang, J., Tian, W., Ju, G., ... Song, B. (2015). Electric signals regulate directional migration of ventral midbrain derived dopaminergic neural progenitor cells via Wnt/GSK3β signaling. Experimental Neurology, 263, pp. 113-21. doi:10.1016/j.expneurol.2014.09.014.
Liu J, et al. Electric Signals Regulate Directional Migration of Ventral Midbrain Derived Dopaminergic Neural Progenitor Cells Via Wnt/GSK3β Signaling. Exp Neurol. 2015;263:113-21. PubMed PMID: 25265211.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Electric signals regulate directional migration of ventral midbrain derived dopaminergic neural progenitor cells via Wnt/GSK3β signaling. AU - Liu,Jia, AU - Zhu,Bangfu, AU - Zhang,Gaofeng, AU - Wang,Jian, AU - Tian,Weiming, AU - Ju,Gong, AU - Wei,Xiaoqing, AU - Song,Bing, Y1 - 2014/09/28/ PY - 2014/03/05/received PY - 2014/07/16/revised PY - 2014/09/16/accepted PY - 2014/9/30/entrez PY - 2014/9/30/pubmed PY - 2015/2/11/medline KW - Dopaminergic neurons KW - Electric fields KW - Migration KW - Neural progenitor cell KW - Ventral midbrain KW - Wnt/GSK3β signaling pathway SP - 113 EP - 21 JF - Experimental neurology JO - Exp. Neurol. VL - 263 N2 - Neural progenitor cell (NPC) replacement therapy is a promising treatment for neurodegenerative disorders including Parkinson's disease (PD). It requires a controlled directional migration and integration of NPCs, for example dopaminergic (DA) progenitor cells, into the damaged host brain tissue. There is, however, only limited understanding of how to regulate the directed migration of NPCs to the diseased or damaged brain tissues for repair and regeneration. The aims of this study are to explore the possibility of using a physiological level of electrical stimulation to regulate the directed migration of ventral midbrain NPCs (NPCs(vm)), and to investigate their potential regulation via GSK3β and associated downstream effectors. We tested the effects of direct-current (DC) electric fields (EFs) on the migration behavior of the NPCs(vm). A DC EF induced directional cell migration toward the cathode, namely electrotaxis. Reversal of the EF polarity triggered a sharp reversal of the NPC(vm) electrotaxis. The electrotactic response was both time and EF voltage dependent. Pharmacologically inhibiting the canonical Wnt/GSK3β pathway significantly reduced the electrotactic response of NPCs(vm), which is associated with the down-regulation of GSK3β phosphorylation, β-catenin activation and CLASP2 expression. This was further proved by RNA interference of GSK3β, which also showed a significantly reduced electrotactic response in association with reduced β-catenin activation and CLASP2 expression. In comparison, RNA interference of β-catenin slightly reduced electrotactic response and CLASP2 expression. Both pharmacological inhibition of Wnt/GSK3β and RNA interference of GSK3β/β-catenin clearly reduced the asymmetric redistribution of CLASP2 and its co-localization with α-tubulin. These results suggest that Wnt/GSK3β signaling contributes to the electrotactic response of NPCs(vm) through the coordination of GSK3β phosphorylation, β-catenin activation, CLASP2 expression and asymmetric redistribution to the leading edge of the migrating cells. SN - 1090-2430 UR - https://www.unboundmedicine.com/medline/citation/25265211/Electric_signals_regulate_directional_migration_of_ventral_midbrain_derived_dopaminergic_neural_progenitor_cells_via_Wnt/GSK3β_signaling_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4886(14)00297-0 DB - PRIME DP - Unbound Medicine ER -