Mind Over Magnet: Cryptochrome Proteins Enable Magnetic Brain Repair

As anyone who has played with Geomag as a child, had an MRI scan, or watched that episode of Breaking Bad can attest, magnets are both very cool and potentially, very powerful.

A new study conducted by researchers at Paris’s Sorbonne University, alongside colleagues from the US and Australia has now suggested that magnetic stimulation may be able to help the brain repair itself. What’s more, the team has gone one step further by identifying a molecule that they suggest may mediate this healing effect.

To identify this magnet-sensitive molecule, the team actually looked beyond the brain. “There’s a general tendency to reflect the idea that the brain is so special that you need to be specific,” says Jean Mariani, a Professor at Sorbonne University and co-author of the study, which was published in Science Advances. He explains that the molecule, a protein called cryptochrome, is located throughout cells in the body, not just the brain. Cryptochrome has a dual function in humans, says Mariani, also playing a role in circadian rhythm, which has occupied most research into the protein.

Non-invasive stimulation of the brain has become a hot topic in neurology over the past few years. The two most popular technologies are transcranial direct current stimulation (tDCS), which passes a weak electrical current over particular regions of the brain, and transcranial magnetic stimulation (TMS), which instead uses a magnetic field.

The perfect pattern

Mariani’s team began their research by trialing several different TMS protocols, varying frequency and pattern, to see which was best for inducing repair in a region of the mouse brain called the olivocerebellar path. The neurons in this region are an important part of motor learning networks.

They showed that a TMS regimen of 10 minutes of exposure a day for two weeks was best at inducing repair. The stimulation acted to alter the expression of genes related to growth promotion in the cerebellum and resulted in the reinnervation of Purkinje cells, which are large neurons with an important role in regulating motor coordination.

The team also showed that the ability of the stimulation to induce nerve cell regrowth was dependent on using specific patterns that mimicked those of theta brain waves. Most TMS approaches use regular patterns that don’t mimic biological rhythms. These standard patterns proved unable to stimulate regrowth.

Finally, the team showed that cryptochrome was essential for this regrowth process. In mice who had been genetically modified to lack this protein, magnetic stimulation had no effect on the Purkinje cells. Importantly, the team showed that knocking out cryptochrome in this way did not interfere with other growth processes, as the mice were still able to respond to the pro-growth molecule brain-derived neurotrophic factor (BDNF).

Lower intensity, higher success

Mariani says that the use of a low-intensity form of TMS was key to their approach, as it is more practical than that used clinically: “The one used in the clinics needs you to go to the hospital because you need a special apparatus. Also you use intensity sufficiently high that it’s difficult to do repetitive stimulation because it becomes hot,” explains Mariani.

Mariani highlighted that the low intensity of the stimulation could make the technology incredibly useful to patients recovering from nerve damage. Whilst rehabilitation for these types of injuries is possible in hospital settings, Mariani points out that budget requirements mean that patients are often farmed out before they are properly healed. “In France by law you can stay in this kind of rehabilitation center for only three months,” says Mariani. He hopes that by allowing patients to undergo TMS-like stimulation in a familiar environment, for a longer period of time, recovery will be boosted. “If you can do it at home, it’s a crucial advantage,” says Mariani.

Vincenzo Di Lazarro,  professor of neurology at the Campus Bio-Medico University Hospital in Rome, who was not involved in the study, highlighted TMS research into brain repair remains at an early stage. "The use of rTMS and other techniques such as tDCS or tACS in order to promote human brain repair is still in an exploratory phase and further evidence is needed. Thus, all these techniques that have been termed “electroceuticals” have a great potential but further studies should be performed for new applications," says Di Lazarro.

The sinister side of magnetosensing?

Mariani’s research is still at a preclinical stage, and functional studies – to see whether the nerve cell repair actually improves movement – are still in the works (although Mariani says results are promising). As this research is all carried out using mice, it may take years before an effective TMS, based on this research, is available to consumers.

But maybe they don’t have to wait – many companies are already providing non-invasive brain stimulation devices on the market, claiming they can boost concentration, and even be optimized for particular tasks, like creative writing. I ask Mariani whether we should all go and fork out for one of these kits, like the Platowork device, which uses tDCS and is available on Indiegogo for just over £340.

As tempting as this sounds, Mariani warns against reading too much into the device’s claims. “It is very difficult to judge this specific medtech with very little information on technical characteristics, medical indications or wellness or fitness indications,” says Mariani. Di Lazarro goes further in his criticism, highlighting the potential risks associated with such devices, "In my opinion, any use of NIBS to enhance cognitive or motor performances should be strongly discouraged because there is no evidence that the boosting effects are consistent and also because there is the consistent risk that “do it yourself NIBS” without medical prescription and supervision for specific conditions or outside an approved clinical trial might well exceed the safety limits with unpredictable effects," says Di Lazarro.

Mariani has authored research showing that exposure to the wrong sort of magnetic fields could induce the production of reactive oxygen species, which are potentially toxic to cells. Whilst this paper did not study brain cells, it showed that, as in the nerve cell regrowth study, cryptochromes were involved in the toxic pathways. Mariani suggests this is why we need to fully understand the mechanisms and patterns that are optimal to brain health before firing fields at anyone’s head. “The same tool could be in one case positive and in the other case, if you use without previous knowledge, it might be dangerous,” concludes Mariani.