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High frequency electrical stimulation promotes expression of extracellular matrix proteins from human astrocytes

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Abstract

Therapeutic benefits of deep brain stimulation (DBS), a neurosurgical treatment for certain movement disorders and other neurologic conditions, are well documented, but DBS mechanisms remain largely unexplained. DBS is thought to modulate pathological neural activity. However, although astrocytes, the most numerous cell type in the brain, play a significant role in neurotransmission, chemical homeostasis and synaptic plasticity, their role in DBS has not been fully examined. To investigate astrocytic function in DBS, we applied DBS-like high frequency electrical stimulation for 24 h to human astrocytes in vitro and analyzed single cell transcriptome mRNA profile. We found that DBS-like high frequency stimulation negatively impacts astrocyte metabolism and promotes the release of extracellular matrix (matricellular) proteins, including IGFBP3, GREM1, IGFBP5, THBS1, and PAPPA. Our results suggest that astrocytes are involved in the long-term modulation of extra cellular matrix environments and that they may influence persistent cell-to-cell interaction and help maintain neuromodulation over time.

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Acknowledgements

We thank Dr. Penelope Duffy for her help in preparing this manuscript. This study was funded in part by the National Institutes of Health, National Institute of Neurological Disorders and Strokes (NS 88260). John M. Nasseff, Sr. Career Development Award was granted to SYC.

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Author notes

  1. Jin Sung Jang and Chan-Il Choi contributed equally to the work.

Authors and Affiliations

  1. Medical Genome Facility, Pomona College, Claremont, USA

    Jin Sung Jang & Jin Jen

  2. Department of Neurologic Surgery, Mayo Clinic, Rochester, USA

    Chan-Il Choi & Su-youne Chang

  3. Division of Biology and Biomedical Science, Washington University in St. Louis, St. Louis, USA

    Jiwon Yi

  4. Department of Anatomical Pathology, Mayo Clinic, Rochester, MN, USA

    Kim Butters

  5. Department of Neurology, Mayo Clinic, Rochester, MN, USA

    Inyong Kim

  6. Bioinformatics Core, Mayo Clinic, Rochester, MN, USA

    Aditya Bhagwate

  7. Department of Lab Medicine and Pathology, Mayo Clinic, Rochester, MN, USA

    Jin Sung Jang & Jin Jen

  8. Department of Physiology and Biomedical Engineering, Mayo Clinic, 200 1st Street SW, Rochester, 55905, MN, USA

    Su-youne Chang

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  1. Jin Sung Jang
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Contributions

SYC and JJ conceived and designed the experiments; JSJ and CIC designed and performed the experiments; JY performed experiment; KB performed primary cell culture; JSJ, CIC and AB analyzed the data; IK designed and built the stimulation chamber.

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Correspondence to Su-youne Chang.

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Jang, J.S., Choi, CI., Yi, J. et al. High frequency electrical stimulation promotes expression of extracellular matrix proteins from human astrocytes. Mol Biol Rep 46, 4369–4375 (2019). https://doi.org/10.1007/s11033-019-04890-9

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  • DOI: https://doi.org/10.1007/s11033-019-04890-9

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