Medical/biological study (experimental study)

Neurodevelopmental anomalies of the hippocampus in rats exposed to weak intensity complex magnetic fields throughout gestation med./bio.

By: Fournier NM, Mach QH, Whissell PD, Persinger MA

Published in: Int J Dev Neurosci 2012; 30 (6): 427-433

Aim of study (acc. to author)

To investigate the effect of weak intensity magnetic fields on the prenatal brain development.

Background/further details

Pregnant rats were continuously exposed to one of four intensities during the pregnancy: 1.) 5-20 nT, 2.) 30-50 nT, 3.) 90-580 nT und 4.) 90-1200 nT (n=2 per group). After one year, the male offspring (n=6-7 per group) were used in the open field test and the contextual fear conditioning was examined. Additionally, the number and the structure of hippocampal neurons were analyzed (n=4 per group).
Previous studies showed that there were no differences between rats exposed to a weak magnetic field of 5-20 nT and a control group without any magnetic field. Therefore, in this study, the reference group (5-20 nT) was used as a control.
The experiment was performed twice.

Endpoint

effects on the neurological system: morphology of hippocampus
cognitive/behavioral endpoints: behavior in open field, fear conditioning

Exposure

- 50 Hz
- 50/60 Hz
- magnetic field
- low frequency
- signals/pulses

Exposure	Parameters
Exposure 1: 50 Hz Modulation type: pulsed Exposure duration: continuous to different field patterns for 24 h/day during gestation (21 days)	magnetic flux density: 20 nT maximum (B = 5 - 20 nT reference group) magnetic flux density: 50 nT maximum (B = 30 - 50 nT low-intensity group) magnetic flux density: 580 nT maximum (B = 90 - 580 nT medium-intensity group) magnetic flux density: 1,200 nT maximum (B = 590 - 1200 nT high-intensity group)

Exposure 1

Main characteristics

Frequency	50 Hz
Type	magnetic field
Exposure duration	continuous to different field patterns for 24 h/day during gestation (21 days)
Additional info	temporal structures of a complex magnetic field (composite, LTP-like, and non-sinusoidal 50 Hz field)

Modulation

Modulation type	pulsed
Additional info	composite pattern: composed of 40 sequential 250 ms signatures of specific frequency-modulated patterns as well as of those derived from mathematical relationships; LTP-pattern: repeated sequences of a primer pulse followed 170 ms later by four working pulses; 50 Hz pattern: rise time and fall time of 1 ms and a plateau and trough of 20 ms; all patterns were presented in a repeating cycle for 10 s, followed by 40 s of no field for 24 h before the next pattern was initiated; each pattern repeated every fourth day throughout gestation

Modulation type

pulsed

Additional info

composite pattern: composed of 40 sequential 250 ms signatures of specific frequency-modulated patterns as well as of those derived from mathematical relationships; LTP-pattern: repeated sequences of a primer pulse followed 170 ms later by four working pulses; 50 Hz pattern: rise time and fall time of 1 ms and a plateau and trough of 20 ms; all patterns were presented in a repeating cycle for 10 s, followed by 40 s of no field for 24 h before the next pattern was initiated; each pattern repeated every fourth day throughout gestation

Exposure setup

Exposure source	Helmholtz coils
Setup	rats kept in one of four identical compartments of a 140 cm x 33 cm x 33 cm plastic cage; identical Herlmholtz coils positioned at each end of the cage; coils created by wrapping 38 cm x 33 cm x 27 cm cartons with 305 m of 30 AWG wire

Parameters

Measurand	Value	Type	Method	Mass	Remarks
magnetic flux density	20 nT	maximum	measured	-	B = 5 - 20 nT reference group
magnetic flux density	50 nT	maximum	measured	-	B = 30 - 50 nT low-intensity group
magnetic flux density	580 nT	maximum	measured	-	B = 90 - 580 nT medium-intensity group
magnetic flux density	1,200 nT	maximum	measured	-	B = 590 - 1200 nT high-intensity group

Reference articles

Whissell PD et al. (2009): Prenatal exposures to LTP-patterned magnetic fields: quantitative effects on specific limbic structures and acquisition of contextually conditioned fear
St-Pierre LS et al. (2008): Altered blood chemistry and hippocampal histomorphology in adult rats following prenatal exposure to physiologically-patterned, weak (50-500 nanoTesla range) magnetic fields
St-Pierre LS et al. (2003): Conspicuous histomorphological anomalies in the hippocampal formation of rats exposed prenatally to a complex sequenced magnetic field within the nanoTesla range

Exposed system:

animal
rat/Wistar albino
whole body: in utero

Methods Endpoint/measurement parameters/methodology

effects on the neurological system: morphology and number of neurons and glial cells in hippocampus (light microscopy)
cognitive/behavioral endpoints: frequency of locomotor activity, grooming, rearing, urination, defection in open field; freezing time (fear conditioning)

Investigated system:

tissue slices
investigation on living organism

Investigated organ system:

brain/CNS

Time of investigation:

after exposure

Main outcome of study (acc. to author)

Individual analyses of open field related behaviors revealed no significant differences between any of the exposure conditions. In the fear conditioning, it was found that exposure to the low-intensity (30-50 nT) complex magnetic field during prenatal development resulted in a significant reduction of freezing time compared to the reference group (5-20 nT). Additionally, rats exposed to the low-intensity (30-50 nT) complex magnetic field showed anomalies in the cytological and morphological development of the hippocampus (reduction in overall hippocampal size and promoted subtle malformation of some regions) as compared to the reference group (5-20 nT). In contrast, exposure to weaker or stronger intensities of the same complex magnetic field did not interfere with hippocampal development or anxiety behavior.
These findings suggest that prenatal exposure to complex magnetic fields of a narrow intensity window during development could result in subtle but permanent alterations in hippocampal structure and function.

Study character:

medical/biological study
experimental study
full/main study
blind study (only morphological examination of brain)

Study funded by

Canadian Institutes of Health Research (CIHR)
Natural Sciences and Engineering Research Council (NSERC) of Canada

Salunke BP et al. (2014): Involvement of NMDA receptor in low-frequency magnetic field-induced anxiety in mice
Hemmati M et al. (2014): Effects of electromagnetic fields on Reelin and Dab1 expression in the developing cerebral cortex
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St-Pierre LS et al. (2008): Behavioral Changes in Adult Rats After Prenatal Exposures to Complex, Weak Magnetic Fields
McKay BE et al. (2003): Radial maze proficiency of adult Wistar rats given prenatal complex magnetic field treatments
St-Pierre LS et al. (2003): Conspicuous histomorphological anomalies in the hippocampal formation of rats exposed prenatally to a complex sequenced magnetic field within the nanoTesla range
Yu MC et al. (1993): Effects of 60 Hz electric and magnetic fields on maturation of the rat neopallium
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