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Piezoelectric Ceramic (PZT) Modulates Axonal Guidance Growth of Rat Cortical Neurons via RhoA, Rac1, and Cdc42 Pathways

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Abstract

Electrical stimulation is critical for axonal connection, which can stimulate axonal migration and deformation to promote axonal growth in the nervous system. Netrin-1, an axonal guidance cue, can also promote axonal guidance growth, but the molecular mechanism of axonal guidance growth under indirect electric stimulation is still unknown. We investigated the molecular mechanism of axonal guidance growth under piezoelectric ceramic lead zirconate titanate (PZT) stimulation in the primary cultured cortical neurons. PZT induced marked axonal elongation. Moreover, PZT activated the excitatory postsynaptic currents (EPSCs) by increasing the frequency and amplitude of EPSCs of the cortical neurons in patch clamp assay. PZT downregulated the expression of Netrin-1 and its receptor Deleted in Colorectal Cancer (DCC). Rho GTPase signaling is involved in interactions of Netrin-1 and DCC. PZT activated RhoA. Dramatic decrease of Cdc42 and Rac1 was also observed after PZT treatment. RhoA inhibitor Clostridium botulinum C3 exoenzyme (C3-Exo) prevented the PZT-induced downregulation of Netrin-1 and DCC. We suggest that PZT can promote axonal guidance growth by downregulation of Netrin-1 and DCC to mediate axonal repulsive responses via the Rho GTPase signaling pathway. Obviously, piezoelectric materials may provide a new approach for axonal recovery and be beneficial for clinical therapy in the future.

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Acknowledgments

This work was sponsored by funds from NSFC Research Grant (no. 31100666). The authors would like to thank Dr. Colin McClean for his help in language editing.

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Authors and Affiliations

  1. Underwater Acoustic Transducer and Testing Laboratory, Institute of Acoustics, Chinese Academy of Sciences, Beijing, 100190, China

    Jianqiang Wen

  2. Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing, 100191, China

    Meili Liu

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  1. Jianqiang Wen
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  2. Meili Liu
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Correspondence to Jianqiang Wen.

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Jianqiang Wen and Meili Liu contributed equally to this work.

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Wen, J., Liu, M. Piezoelectric Ceramic (PZT) Modulates Axonal Guidance Growth of Rat Cortical Neurons via RhoA, Rac1, and Cdc42 Pathways. J Mol Neurosci 52, 323–330 (2014). https://doi.org/10.1007/s12031-013-0149-7

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  • DOI: https://doi.org/10.1007/s12031-013-0149-7

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