Perturbing Circadian Oscillations in an In Vitro Suprachiasmatic Nucleus With Magnetic Stimulation

Bioelectromagnetics. 2020 Jan;41(1):63-72. doi: 10.1002/bem.22235.

Abstract

Many neurological disorders are associated with abnormal oscillatory dynamics. The suprachiasmatic nucleus (SCN) is responsible for the timing and synchronization of physiological processes. We performed experiments on PERIOD2::LUCIFERASE transgenic "knock-in" mice. In these mice, a gene that is expressed in a circadian pattern is fused to an inserted gene that codes for luciferase, which is a bioluminescent enzyme. A one-time 3 min magnetic stimulation (MS) was applied to excised slices of the SCN. The MS consisted of a 50-mT field that was turned on and off 4,500 times. The rise time and fall time of the field were 75 μs. A photon count that extended over the full 5 days that the slice remained viable, subsequently revealed how the MS affected the circadian cycle. The MS was applied at points in the circadian cycle that correspond to either maximal or minimal bioluminescence. It was found that both the amplitude and period of the endogenous circadian oscillation are affected by MS and that the effects strongly depend on where in the circadian cycle the stimulation was applied. Our MS dose is in the same range as clinically applied doses, and our findings imply that transcranial MS may be instrumental in remedying disorders that originate in circadian rhythm abnormalities. Bioelectromagnetics. 2020;41:63-72 © 2019 Wiley Periodicals, Inc.

Keywords: PERIOD2::LUCIFERASE transgenic mice; bioluminescence recording; circadian rhythm; suprachiasmatic nucleus slice; transcranial magnetic stimulation.

MeSH terms

  • Animals
  • Biological Clocks / radiation effects
  • Brain
  • Dissection
  • Fluorescent Dyes / metabolism
  • Luciferases / metabolism
  • Luminescent Measurements
  • Magnetic Phenomena*
  • Mice, Transgenic
  • Suprachiasmatic Nucleus / radiation effects*
  • Time Factors

Substances

  • Fluorescent Dyes
  • Luciferases