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Medical/biological study (experimental study)

Olfactory memory is enhanced in mice exposed to extremely low-frequency electromagnetic fields via Wnt/β-catenin dependent modulation of subventricular zone neurogenesis.

Published in: Sci Rep 2018; 8 (1): 262

Aim of study (acc. to author)

To investigate the effect of a 50 Hz magnetic field on olfactory memory and hippocampal neurogenesis in mice as well as the role of the Wnt/β-catenin signal pathway.
Background/further details: In the adult mammalian brain, neurogenesis occurs in the subventricular zone (between striatum and lateral ventricles) and the dentate gyrus of the hippocampus. The Wnt/β-catenin pathway plays a pivotal role in the regulation of cell proliferation, differentiation, genetic stability, migration, and apoptosis and seems also to be important for neurogenesis.
For in vivo tests, mice were randomly divided into two groups: A sham exposure group and a magnetic field exposed group. Several behavioral tests and neuronal examinations were performed with 7-10 animals per group, respectively. Partially the mice were injected with the Wnt inhibitor Dkk-1. The expression of neuronal genes was examined in 3 animals per group, respectively.
To further examine the molecular mechanisms, in vitro tests with neural stem cells were performed.

Endpoint

Exposure

Exposure Parameters
Exposure 1: 50 Hz
Exposure duration: 3.5 hours/day for 12 days
Exposure 2: 50 Hz
Exposure duration: 3.5 hours/day for 4 days
in vivo gene expression experiments, western blot and immunofluorescence of β-catenin
Exposure 3: 50 Hz
Exposure duration: 3, 6, or 24 hours
in vitro experiments
Exposure 1
Main characteristics
Frequency 50 Hz
Type
Exposure duration 3.5 hours/day for 12 days
Additional info in vivo behavioral and immunofluorescence experiments
Exposure setup
Exposure source
Chamber plastic housing cages containing mice were placed inside the solenoid
Setup magnetic field was generated by a solenoid surrounding a plexiglas cylinder (diameter 20 cm; length 42 cm)
Sham exposure A sham exposure was conducted.
Additional info mice of the control group were also put in the solenoid for sham exposure, but the power generator was switched off
Parameters
Measurand Value Type Method Mass Remarks
magnetic flux density 1 mT - - - -
Exposure 2
Main characteristics
Frequency 50 Hz
Type
Exposure duration 3.5 hours/day for 4 days
Additional info in vivo gene expression experiments, western blot and immunofluorescence of β-catenin
Exposure setup
Exposure source
Sham exposure A sham exposure was conducted.
Parameters
Measurand Value Type Method Mass Remarks
magnetic flux density 1 mT - - - -
Exposure 3
Main characteristics
Frequency 50 Hz
Type
Exposure duration 3, 6, or 24 hours
Additional info in vitro experiments
Exposure setup
Exposure source
Setup the solenoid was placed in the CO2 incubator
Parameters
Measurand Value Type Method Mass Remarks
magnetic flux density 1 mT - - - -
Reference articles
  • Leone L et al. (2014): Epigenetic modulation of adult hippocampal neurogenesis by extremely low-frequency electromagnetic fields.
  • Cuccurazzu B et al. (2010): Exposure to extremely low-frequency (50 Hz) electromagnetic fields enhances adult hippocampal neurogenesis in C57BL/6 mice.
Exposed system:

Methods Endpoint/measurement parameters/methodology

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

Main outcome of study (acc. to author)

Magnetic field exposed mice showed a significantly enhanced odor discrimination and olfactory memory compared to sham exposed mice as well as a significantly increased neurogenesis in the subventricular zone. This was accompanied by significantly increased mRNA levels of Wnt3, Hes1, and Mash1 in the subventricular zone of exposed mice as well as in neuronal stem cells of the subventricular zone (in vitro) when compared with the corresponding control group, while in the hippocampus of exposed mice only Hes1 and Mash1 were significantly up-regulated. The level of β-catenin (downstream target of Wnt3) was significantly increased in the nuclei of exposed neural stem cells (in vitro) compared to sham exposed cells. The Wnt inhibitor Dkk-1 abolished the magnetic field induced increases in neurogenesis (in vivo), olfactory memory (in vivo) and up-regulation of Wnt3, Hes1, and Mash1 (in vitro). Additionally, Dkk-1 significantly decreased the level of β-catenin in the nucleus of cells in the subventricular zone compared to those without Dkk-1, while no effect was seen in the hippocampus.
The authors conclude that 50 Hz magnetic fields could improve the olfactory memory of mice via the Wnt/β-catenin signal pathway in the subventricular zone.
Study character:

Study funded by

  • Istituto Nazionale Per L'Assicurazione Contro Gli Infortuni Sul Lavoro (INAIL; Italian Workers' Compensation Authority), Italy

Related articles

  • Sakhaie MH et al. (2017): Effects of Extremely Low-Frequency Electromagnetic Fields on Neurogenesis and Cognitive Behavior in an Experimental Model of Hippocampal Injury.
  • Bernal-Mondragón C et al. (2016): Effects of repeated 9 and 30-day exposure to extremely low-frequency electromagnetic fields on social recognition behavior and estrogen receptors expression in olfactory bulb of Wistar female rats.
  • Hu Y et al. (2016): Long-term exposure to ELF-MF ameliorates cognitive deficits and attenuates tau hyperphosphorylation in 3xTg AD mice.
  • Li C et al. (2014): The extremely low-frequency magnetic field exposure differently affects the AMPAR and NMDAR subunit expressions in the hippocampus, entorhinal cortex and prefrontal cortex without effects on the rat spatial learning and memory.
  • Podda MV et al. (2014): Extremely low-frequency electromagnetic fields enhance the survival of newborn neurons in the mouse hippocampus.
  • Leone L et al. (2014): Epigenetic modulation of adult hippocampal neurogenesis by extremely low-frequency electromagnetic fields.
  • Cuccurazzu B et al. (2010): Exposure to extremely low-frequency (50 Hz) electromagnetic fields enhances adult hippocampal neurogenesis in C57BL/6 mice.