Radical triads, not pairs, may explain effects of hypomagnetic fields on neurogenesis

Abstract

Adult hippocampal neurogenesis and hippocampus-dependent cognition in mice have been found to be adversely affected by hypomagnetic field exposure. The effect concurred with a reduction of reactive oxygen species in the absence of the geomagnetic field. A recent theoretical study suggests a mechanistic interpretation of this phenomenon in the framework of the Radical Pair Mechanism. According to this model, a flavin-superoxide radical pair, born in the singlet spin configuration, undergoes magnetic field-dependent spin dynamics such that the pair’s recombination is enhanced as the applied magnetic field is reduced. This model has two ostensible weaknesses: a) the assumption of a singlet initial state is irreconcilable with known reaction pathways generating such radical pairs, and b) the model neglects the swift spin relaxation of free superoxide, which abolishes any magnetic sensitivity in geomagnetic/hypomagnetic fields. We here suggest that a model based on a radical triad and the assumption of a secondary radical scavenging reaction can, in principle, explain the phenomenon without unnatural assumptions, thus providing a coherent explanation of hypomagnetic field effects in biology.

Hypomagnetic field effects as a potential avenue for testing the radical pair mechanism in biology

“…It should also be noted that an extended version of the radical pair mechanism, the radical triad mechanism [49][50][51], has been proposed as an explanation for weak magnetic field effects. Radical triads may provide more sensitivity and circumvent issues such as weakening effects from dipolar interactions and fast spin relaxation of superoxide.…”

Structural Rearrangements of Pigeon Cryptochrome 4 Undergoing a Complete Redox Cycle

“…5 The formation of FADH • is also the beginning of a reoxidation process which reestablishes the dark state (DS) and primes the protein to start the radical pair formation process anew. 4,15,17 Another redox state associated with the FAD is the fully reduced FADH − , 18−20 which is not considered in this study; it returns to the FADH • state via the means of oxygen 20,21 to finally return to the fully oxidized form. While the RPD state has an expected lifetime of up to 1 μs, 8 the reoxidation pathway of the FAD acts on a scale of more than 100 μs.…”