Static Magnetic Field Stimulation Enhances Oligodendrocyte Differentiation and Secretion of Neurotrophic Factors

Ankshita Prasad; Daniel B Loong Teh; Agata Blasiak; Chou Chai; Yang Wu; Payam M Gharibani; In Hong Yang; Thang T Phan; Kah Leong Lim; Hyunsoo Yang; Xiaogang Liu; Angelo H All

doi:10.1038/s41598-017-06331-8

Static Magnetic Field Stimulation Enhances Oligodendrocyte Differentiation and Secretion of Neurotrophic Factors

Sci Rep. 2017 Jul 27;7(1):6743. doi: 10.1038/s41598-017-06331-8.

Authors

Ankshita Prasad¹, Daniel B Loong Teh², Agata Blasiak², Chou Chai³, Yang Wu⁴, Payam M Gharibani⁵, In Hong Yang^{2

5}, Thang T Phan⁶, Kah Leong Lim^{3

7

8}, Hyunsoo Yang⁴, Xiaogang Liu⁹, Angelo H All^{10

11}

Affiliations

¹ Department of Biomedical Engineering, National University of Singapore, E4, 4 Engineering Drive 3, Singapore, 117583, Singapore.
² Singapore Institute of Neurotechnology (SINAPSE), National University of Singapore, 28 Medical Drive, 5-COR, Singapore, 117456, Singapore.
³ National Neuroscience Institute, 11 Jalan Tan Tock Seng, Singapore, 308433, Singapore.
⁴ Department of Electrical and Computer Engineering, National University of Singapore, 4 Engineering Drive 3, Singapore, 117583, Singapore.
⁵ Department of Biomedical Engineering, John Hopkins School of Medicine, 701C Rutland Avenue 720, Baltimore, MD, 21205, USA.
⁶ Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119228, Singapore.
⁷ Department of Physiology, 2 Medical Drive, MD9, National University of Singapore, 117593, Singapore, Singapore.
⁸ Duke-NUS Medical School. 8 College Road, 169857, Singapore, Singapore.
⁹ Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore, 117543, Singapore. [email protected].
¹⁰ Department of Biomedical Engineering, John Hopkins School of Medicine, 701C Rutland Avenue 720, Baltimore, MD, 21205, USA. [email protected].
¹¹ Department of Neurology, John Hopkins School of Medicine, 701C Rutland Avenue 720, Baltimore, MD, 21205, USA. [email protected].

Abstract

The cellular-level effects of low/high frequency oscillating magnetic field on excitable cells such as neurons are well established. In contrast, the effects of a homogeneous, static magnetic field (SMF) on Central Nervous System (CNS) glial cells are less investigated. Here, we have developed an in vitro SMF stimulation set-up to investigate the genomic effects of SMF exposure on oligodendrocyte differentiation and neurotrophic factors secretion. Human oligodendrocytes precursor cells (OPCs) were stimulated with moderate intensity SMF (0.3 T) for a period of two weeks (two hours/day). The differential gene expression of cell activity marker (c-fos), early OPC (Olig1, Olig2. Sox10), and mature oligodendrocyte markers (CNP, MBP) were quantified. The enhanced myelination capacity of the SMF stimulated oligodendrocytes was validated in a dorsal root ganglion microfluidics chamber platform. Additionally, the effects of SMF on the gene expression and secretion of neurotrophic factors- BDNF and NT3 was quantified. We also report that SMF stimulation increases the intracellular calcium influx in OPCs as well as the gene expression of L-type channel subunits-CaV1.2 and CaV1.3. Our findings emphasize the ability of glial cells such as OPCs to positively respond to moderate intensity SMF stimulation by exhibiting enhanced differentiation, functionality as well as neurotrophic factor release.

Publication types

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

MeSH terms

2',3'-Cyclic Nucleotide 3'-Phosphodiesterase / genetics
2',3'-Cyclic Nucleotide 3'-Phosphodiesterase / metabolism
Animals
Basic Helix-Loop-Helix Transcription Factors / genetics
Basic Helix-Loop-Helix Transcription Factors / metabolism
Biomarkers / metabolism
Brain-Derived Neurotrophic Factor / genetics
Brain-Derived Neurotrophic Factor / metabolism*
Calcium / metabolism*
Calcium Channels, L-Type / genetics
Calcium Channels, L-Type / metabolism
Cell Differentiation
Embryo, Mammalian
Ganglia, Spinal / cytology
Ganglia, Spinal / metabolism
Gene Expression Regulation
Humans
Induced Pluripotent Stem Cells / cytology
Induced Pluripotent Stem Cells / metabolism*
Magnetic Fields*
Microfluidic Analytical Techniques
Myelin Basic Protein / genetics
Myelin Basic Protein / metabolism*
Nerve Growth Factors / genetics
Nerve Growth Factors / metabolism
Nerve Tissue Proteins / genetics
Nerve Tissue Proteins / metabolism
Neurotrophin 3
Oligodendrocyte Transcription Factor 2 / genetics
Oligodendrocyte Transcription Factor 2 / metabolism
Oligodendroglia / cytology
Oligodendroglia / metabolism*
Primary Cell Culture
Proto-Oncogene Proteins c-fos / genetics
Proto-Oncogene Proteins c-fos / metabolism
Rats
Rats, Sprague-Dawley
SOXE Transcription Factors / genetics
SOXE Transcription Factors / metabolism

Substances

Basic Helix-Loop-Helix Transcription Factors
Biomarkers
Brain-Derived Neurotrophic Factor
CACNA1C protein, human
CACNA1D protein, human
Calcium Channels, L-Type
Myelin Basic Protein
NTF3 protein, human
Nerve Growth Factors
Nerve Tissue Proteins
Neurotrophin 3
OLIG1 protein, human
OLIG2 protein, human
Oligodendrocyte Transcription Factor 2
Proto-Oncogene Proteins c-fos
SOX10 protein, human
SOXE Transcription Factors
BDNF protein, human
2',3'-Cyclic Nucleotide 3'-Phosphodiesterase
CNP protein, human
Calcium