研究のタイプ: 医学/生物学の研究 (experimental study)

[EGR1は超低周波電磁界が誘導する神経細胞分化を仲介した] med./bio.

Egr1 mediated the neuronal differentiation induced by extremely low-frequency electromagnetic fields.

掲載誌: Life Sci 2014; 102 (1): 16-27

この研究は、超低周波磁界(ELF-MF)が神経細胞分化誘導するとの仮説に立ち、そのメカニズムを検討した。ヒト骨髄間葉幹細胞(hBM-MSCs)にELF-MF(50Hz、1mT)を8日間ばく露し、一般的な分子生物学的分析(免疫蛍光法、定量的RT-PCR.)および遺伝子発現の分析を行った。その結果、ELF-MF誘導神経細胞分化における重要な転写因子の一つである初期増殖応答タンパク質1(Egr1)が見出された、と報告している。

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研究目的(著者による)

The effect of exposure of different stem cells types to extremely low frequency magnetic fields on neuronal differentiation in relation to gene expression should be investigated.

詳細情報

The study was conducted in the view of a possible therapeutic use for transplantations to treat neurodegenerative diseases.
Human bone marrow-derived mesenchymal stem cells and mouse neural stem cells were either exposed to different magnetic fields (0-200 Hz; exposure groups) or not exposed (control groups). Additionally, tests were conducted with Egr1-knockdown and Egr1-overexpressing human bone marrow-mesenchymal stem cells as Egr1 was supposed to play a crucial role in magnetic field mediated neuronal differentiation.
Finally, tests were conducted with mice, in which the loss of dopaminergic neurons in Parkinson's disease was simulated by the administration of 6-hydroxy-dopamine (6-OHDA). The mice were divided into the following groups: 1) only administration of 6-OHDA, 2) 6-OHDA and sham transplantation, 3) 6-OHDA and transplantation of human bone marrow-mesenchymal stem cells, 4) 6-OHDA and transplantation of Egr1-overexpressing human bone marrow-mesenchymal stem cells, 5) 6-OHDA, transplantation of Egr1-overexpressing human bone marrow-mesenchymal stem cells and subsequent exposure to the magnetic field, 6) 6-OHDA and transplantation of embryonic midbrain cells (positive control). Stem cell transplantations were conducted 4 weeks after injection of 6-OHDA and mice were exposed afterwards.

影響評価項目

ばく露

ばく露 パラメータ
ばく露1: 0–200 Hz
ばく露時間: continuous for 8 days with 0, 50, 100 or 200 Hz
pretest (with human stem cells)
ばく露2: 50 Hz
ばく露時間: continuous for 8 days
human stem cells
ばく露3: 50 Hz
ばく露時間: continuous for 6 days
mouse stem cells
ばく露4: 50 Hz
ばく露時間: continuous for 1 day every other day for 4 weeks
mice

ばく露1

主たる特性
周波数 0–200 Hz
タイプ
  • magnetic field
波形
  • sinusoidal
ばく露時間 continuous for 8 days with 0, 50, 100 or 200 Hz
Additional information pretest (with human stem cells)
ばく露装置
ばく露の発生源/構造
ばく露装置の詳細 cells were exposed in 35 mm cell culture plates in a system formed by two Helmholtz coils (15 cm inner diameter), which produced a vertical magnetic field in a cell culture incubator with 5% CO2 at 37°C
Additional information control cultures were grown in a separate incubator without Helmholtz coils
パラメータ
測定量 種別 Method Mass 備考
磁束密度 1 mT - 測定値 - -

ばく露2

主たる特性
周波数 50 Hz
タイプ
  • magnetic field
波形
  • sinusoidal
ばく露時間 continuous for 8 days
Additional information human stem cells
ばく露装置
ばく露の発生源/構造
  • E1と同じ装置
パラメータ
測定量 種別 Method Mass 備考
磁束密度 1 mT - 測定値 - -

ばく露3

主たる特性
周波数 50 Hz
タイプ
  • magnetic field
波形
  • sinusoidal
ばく露時間 continuous for 6 days
Additional information mouse stem cells
ばく露装置
ばく露の発生源/構造
  • E1と同じ装置
パラメータ
測定量 種別 Method Mass 備考
磁束密度 1 mT - 測定値 - -

ばく露4

主たる特性
周波数 50 Hz
タイプ
  • magnetic field
波形
  • sinusoidal
ばく露時間 continuous for 1 day every other day for 4 weeks
Additional information mice
ばく露装置
ばく露の発生源/構造
ばく露装置の詳細 mice were exposed in 2 plastic cages in a system formed by two Helmholtz coils, which produced a horizontal magnetic field
パラメータ
測定量 種別 Method Mass 備考
磁束密度 2 mT - 測定値 - -

Reference articles

ばく露を受けた生物:

方法 影響評価項目/測定パラメータ/方法

研究対象とした生物試料:
研究対象とした臓器系:
調査の時期:
  • ばく露前
  • ばく露中
  • ばく露後

研究の主なアウトカム(著者による)

In the pretest (field 1), a significant increase of TuJ1 was observed in cells exposed to the 50 Hz magnetic field compared to cells exposed to the other magnetic fields.
Human stem cells (field 2) showed a significant increase of TuJ1 and NeuroD1 compared to the control group and moreover, these cells showed a neuronal morphology. Additionally, these cells showed electrophysiological properties after exposure comparable to those of primary neurons.
In exposed mouse stem cells (field 3), a significant increase of the TuJ1 and TH protein expression as well as a neuronal morphology were observed compared to the control.
A total of 57 genes were up-regulated in exposed human and mouse stem cells (fields 2+3) compared to the control groups with Egr1 showing the highest up-regulation in both cell types. Egr1-overexpressing cells showed a high degree of neuronal differentiation after exposure to the magnetic field (field 2) with significant increases of the expression of neuronal marker genes compared to the control group, whereas the Egr1-knockdown cells did not show neuronal differentiation and no significant increase of the expression of neuronal marker genes compared to the control.
The apomorphine-induced turning behavior of mice was significantly reduced in group 5 after exposure to the magnetic field (field 4) compared to mice without transplantation (group 1+2) or without exposure (groups 3+4), indicating a replacement of destroyed neurons and neuronal differentiation of injected cells in vivo, which was confirmed by immunofluorescence.
The authors conclude that Egr1 could induce a 50 Hz magnetic field mediated neuronal differentiation of stem cells.

研究の種別:

研究助成

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