Genetic analysis of circadian responses to low frequency electromagnetic fields in Drosophila melanogaster.

PLoS genetics · 2014 · Mixed · Low evidence

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MixedLow evidencePaper 4647

Study snapshot

PublicationPLoS genetics · 2014

Study typeanimal

Reported directionMixed

Evidence ratingLow

Abstract

The blue-light sensitive photoreceptor cryptochrome (CRY) may act as a magneto-receptor through formation of radical pairs involving a triad of tryptophans. Previous genetic analyses of behavioral responses of Drosophila to electromagnetic fields using conditioning, circadian and geotaxis assays have lent some support to the radical pair model (RPM). Here, we describe a new method that generates consistent and reliable circadian responses to electromagnetic fields that differ substantially from those already reported. We used the Schuderer apparatus to isolate Drosophila from local environmental variables, and observe extremely low frequency (3 to 50 Hz) field-induced changes in two locomotor phenotypes, circadian period and activity levels. These field-induced phenotypes are CRY- and blue-light dependent, and are correlated with enhanced CRY stability. Mutational analysis of the terminal tryptophan of the triad hypothesised to be indispensable to the electron transfer required by the RPM reveals that this residue is not necessary for field responses. We observe that deletion of the CRY C-terminus dramatically attenuates the EMF-induced period changes, whereas the N-terminus underlies the hyperactivity. Most strikingly, an isolated CRY C-terminus that does not encode the Tryptophan triad nor the FAD binding domain is nevertheless able to mediate a modest EMF-induced period change. Finally, we observe that hCRY2, but not hCRY1, transformants can detect EMFs, suggesting that hCRY2 is blue light-responsive. In contrast, when we examined circadian molecular cycles in wild-type mouse suprachiasmatic nuclei slices under blue light, there was no field effect. Our results are therefore not consistent with the classical Trp triad-mediated RPM and suggest that CRYs act as blue-light/EMF sensors depending on trans-acting factors that are present in particular cellular environments.

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AI evidence extraction

Structured fields below were generated from the paper’s abstract and metadata to make the evidence easier to inspect. Automated extraction may be incomplete or incorrect; verify important details against the original paper.

Study typeanimal

Effect directionmixed

PopulationDrosophila melanogaster; also includes mouse suprachiasmatic nuclei slices and human cryptochrome (hCRY1/hCRY2) transformants (as described)

Sample sizeNot supplied

ExposureELF

Evidence strengthLowConfidence: 74% · Peer reviewed: yes

Main findings

Using a method intended to control environmental variables, extremely low frequency (3–50 Hz) electromagnetic fields induced changes in Drosophila circadian period and activity levels that were dependent on CRY and blue light and correlated with enhanced CRY stability. Mutational and deletion analyses suggested the responses were not consistent with a classical tryptophan-triad-mediated radical pair model; hCRY2 (not hCRY1) transformants showed EMF detection, while mouse SCN slices under blue light showed no field effect on circadian molecular cycles.

Outcomes measured

Circadian period
Locomotor activity levels (hyperactivity)
Cryptochrome (CRY) stability
Circadian molecular cycles in mouse suprachiasmatic nuclei slices

Limitations

Sample size not reported in the abstract.
Exposure intensity/field strength and exposure duration not reported in the abstract.
Findings include multiple systems (flies, transformants, mouse SCN slices) with differing results, limiting generalization from any single model.

View raw extracted JSON

{
  "study_type": "animal",
  "exposure": {
    "band": "ELF",
    "source": "laboratory apparatus (Schuderer apparatus)",
    "frequency_mhz": null,
    "sar_wkg": null,
    "duration": null
  },
  "population": "Drosophila melanogaster; also includes mouse suprachiasmatic nuclei slices and human cryptochrome (hCRY1/hCRY2) transformants (as described)",
  "sample_size": null,
  "outcomes": [
    "Circadian period",
    "Locomotor activity levels (hyperactivity)",
    "Cryptochrome (CRY) stability",
    "Circadian molecular cycles in mouse suprachiasmatic nuclei slices"
  ],
  "main_findings": "Using a method intended to control environmental variables, extremely low frequency (3–50 Hz) electromagnetic fields induced changes in Drosophila circadian period and activity levels that were dependent on CRY and blue light and correlated with enhanced CRY stability. Mutational and deletion analyses suggested the responses were not consistent with a classical tryptophan-triad-mediated radical pair model; hCRY2 (not hCRY1) transformants showed EMF detection, while mouse SCN slices under blue light showed no field effect on circadian molecular cycles.",
  "effect_direction": "mixed",
  "limitations": [
    "Sample size not reported in the abstract.",
    "Exposure intensity/field strength and exposure duration not reported in the abstract.",
    "Findings include multiple systems (flies, transformants, mouse SCN slices) with differing results, limiting generalization from any single model."
  ],
  "evidence_strength": "low",
  "confidence": 0.74,
  "peer_reviewed_likely": "yes",
  "keywords": [
    "cryptochrome",
    "CRY",
    "blue light",
    "radical pair model",
    "tryptophan triad",
    "extremely low frequency",
    "3–50 Hz",
    "circadian period",
    "locomotor activity",
    "Drosophila melanogaster",
    "mouse suprachiasmatic nucleus",
    "hCRY2",
    "hCRY1"
  ],
  "suggested_hubs": [
    {
      "slug": "elf-emf",
      "weight": 0.86,
      "reason": "Exposure described as extremely low frequency electromagnetic fields (3–50 Hz) with biological effects in an animal model."
    }
  ]
}

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AI-extracted fields are generated from the abstract and metadata and may be incomplete or incorrect. This material is for informational purposes and is not medical advice.

Identifiers and source

DOI: 10.1371/journal.pgen.1004804
PubMed: 25473952

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