Study type: Medical/biological study (experimental study)

Epigenetic modulation of adult hippocampal neurogenesis by extremely low-frequency electromagnetic fields. med./bio.

Published in: Mol Neurobiol 2014; 49 (3): 1472-1486

Aim of study (acc. to author)

To investigate the effects of extremely low frequency magnetic fields on spatial memory and learning in mice as well as its underlying molecular mechanisms.

Background/further details

In previous studies, the authors reported that mice exposed to extremely low frequency magnetic fields showed an increased neurogenesis in the hippocampus (e.g. Podda et al., 2014). Further understanding of this phenomen could help to develop novel therapeutic approaches in the treatment of neurological disorders.
For an in vivo experiment, mice (n=38) were randomly divided into an exposure and a sham exposure group. Different examinations were performed:
1.) For immunohistochemical analysis, 7 mice from each group received daily injections of 100 mg bromodeoxyuridine per kg body weight before each exposure (12 days). Mice were killed 1 day (n=4) or 40 days (n=3) after the last exposure or sham exposure session and the brain was taken for examinations.
2.) 30 days after the last exposure (n=16) or sham exposure (n=14) session, the Morris water maze was performed.
3.) 36 days after the last exposure or sham exposure session, the novel recognition test was performed (each n=8).
For an in vitro experiment, neural stem cells were cultivated in an incubator while exposed or sham exposed. Partially, the calcium channel blocker nifedipine was added to the cell cultures. Different examinations were performed:
1.) For proliferation and immunohistochemical analysis, cells were exposed or sham exposed for 6 or 24 hours while cultivated in proliferation medium.
2.) Cells were exposed or sham exposed for up to 10 days in differentiation medium. Gene expression was examined during the first 2 days (after 0, 6, 12, 24, and 48 hours) and protein expression on the first exposure day as well as from day 6 to 10.

Endpoint

Exposure

Exposure Parameters
Exposure 1: 50 Hz
Exposure duration: 3.5 hours per day for 12 days
Exposure 2: 50 Hz
Exposure duration: 6, 12 or 24 hours per day for up to 10 days

Exposure 1

Main characteristics
Frequency 50 Hz
Type
Waveform
Exposure duration 3.5 hours per day for 12 days
Additional info in vivo
Exposure setup
Exposure source
Chamber 3 to 4 animals in a plastic cage (33 Π15 Π13 cm) which was put in the solenoid
Setup solenoid was made of copper wire wrapped around a Plexiglas cylinder (diameter 20 cm; length 42 cm) with open extremities in which the cage was positioned; geometry of the system assured field uniformity within the entire length of the cage
Sham exposure A sham exposure was conducted.
Parameters
Measurand Value Type Method Mass Remarks
magnetic flux density 1 mT - - - -

Exposure 2

Main characteristics
Frequency 50 Hz
Type
Waveform
Exposure duration 6, 12 or 24 hours per day for up to 10 days
Additional info in vitro
Exposure setup
Exposure source
Setup solenoid was placed inside an CO2 incubator
Sham exposure A sham exposure was conducted.
Additional info control cell cultures were put in another incubator; maximum temperature increase due to exposure was 0.4°C ± 0.1°C
Parameters
Measurand Value Type Method Mass Remarks
magnetic flux density 1 mT - - - -

Reference articles

  • Podda MV et al. (2014): Extremely low-frequency electromagnetic fields enhance the survival of newborn neurons in the mouse hippocampus.
  • Cuccurazzu B et al. (2010): Exposure to extremely low-frequency (50 Hz) electromagnetic fields enhances adult hippocampal neurogenesis in C57BL/6 mice.
  • Hansson Mild K et al. (2009): Exposure of workers to electromagnetic fields. A review of open questions on exposure assessment techniques.
  • Piacentini R et al. (2008): Extremely low-frequency electromagnetic fields promote in vitro neurogenesis via upregulation of Ca(v)1-channel activity.
  • Wolf FI et al. (2005): 50-Hz extremely low frequency electromagnetic fields enhance cell proliferation and DNA damage: possible involvement of a redox mechanism.
  • Grassi C et al. (2004): Effects of 50 Hz electromagnetic fields on voltage-gated Ca2+ channels and their role in modulation of neuroendocrine cell proliferation and death.
  • Czeh B et al. (2002): Chronic psychosocial stress and concomitant repetitive transcranial magnetic stimulation: effects on stress hormone levels and adult hippocampal neurogenesis.

Exposed system:

Methods Endpoint/measurement parameters/methodology

Investigated system:
Investigated organ system:
Time of investigation:
  • during exposure
  • after exposure

Main outcome of study (acc. to author)

In the in vivo experiment, exposed mice showed significantly enhanced memory and learning abilities compared to sham exposed mice. Additionally, immunohistochemistry revealed that the cell proliferation and cell differentiation were significantly increased in the exposed mice in comparison to the sham exposed ones.
Also in the in vitro experiment, in exposed cell cultures, the cell proliferation was significantly higher and the cell differentiation was significantly more enhanced than in sham exposed cell cultures. Additionally, exposure partially led to significant changes in the gene expression of Hes1 (increased after 0 and 24 hours, decreased after 6 and 12 hours), NeuroD1 (increased after 24 hours), Neurogenin1 (increased after 24 and 48 hours) and Mash1 (increased after 0 and 6 hours, decreased after 12 and 48 hours). Furthermore, in a exposed cell cultures, the acetylation of histone and the protein expression of phosphorylated CREB were significantly increased compared to the sham exposure. An addition of nifedipine prevented the exposure-induced effects.
The authors conclude that extremely low frequency magnetic fields could enhance hippocampal neurogenesis and improve learning and memory abilities of mice.

Study character:

Study funded by

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