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Some neurological disorders can be improved through photobiomodulation, a non-invasive technique based on applying low-power light to stimulate altered functions in specific regions of the body. Now, a study published in the Journal of Affective Disorders reveals how photobiomodulation applied to the brain-gut axis is effective in recovering some cognitive alterations and sequelae caused by chronic stress. The work opens new perspectives for applying the technique in future therapies for the treatment of neurological diseases in patients.
The article, based on the study of laboratory animal models, is led by Professor Albert Giralt, from the Faculty of Medicine and Health Sciences and the Institute of Neurosciences (UBneuro) of the University of Barcelona. Teams from the Center for the Production and Validation of Advanced Therapies (CREATIO) of the UB and the University of Girona, as well as the University of Montpellier and the company REGEnLIFE (France) also participate.
Low intensity light to activate the gut-brain axis
In clinical practice, photobiomodulation applies light from lasers or other low-intensity sources to stimulate the activity of an organ with altered physiology. Now, the new study uses, for the first time in the field of depression, combined photobiomodulation to stimulate different organs and, specifically, the brain and the intestine.
«This is one of the most innovative scientific contributions of the new work: co-stimulating the brain and the intestine in a coordinated way at the same time, that is, the brain-gut axis. Nowadays, the research area of the gut-brain axis is generating great scientific interest and is a very promising field for the possible treatment of diseases of the nervous system," details Professor Albert Giralt, also a member of IDIBAPS and the Research Center Biomedical Network of Neurodegenerative Diseases (CIBERNED).
"The new therapeutic approach focuses on this now rediscovered scenario, which is that of intervention and manipulation of the gut-brain axis to address neurological and psychiatric disorders," Giralt continues. «Photobiomodulation is a non-invasive technology, very well tolerated by patients and lacks the side effects of pharmacological treatments. Furthermore, this advance could also be useful in the treatment of pathologies without clear or incomplete medical coverage, such as the treatment-resistant subtype of depression," concludes the expert.
The devices to apply photobiomodulation, developed by the REGEnLIFE company, have been adapted to previous studies related to Alzheimer's patients. They combine multiple stimulation sources (laser, LED, etc.) associated with a magnetic ring to stabilize the emission of pulsed – and not continuous – light to avoid tissue overheating, and are adapted for clinical application in patients.
Psychiatric disorders: beyond the brain
Another scientific milestone of the work is to confirm that psychiatric disorders do not have the brain as their only epicenter, "but other tissues and organs also play a decisive role in their pathophysiology. If the new therapies take all these factors into consideration, it is very likely that we will be able to obtain very satisfactory results in the future," says the researcher.
But how does photobiomodulation act on the brain-gut axis? Until now, only descriptive studies of the changes induced by photobiomodulation were available. Now, the new work delves into the molecular mechanisms and shows how photobiomodulation is capable of reversing the cognitive effects of chronic stress through the restoration of the SIRT1 pathway, "related to senescence and cell death, the modulation of pyramidal neurons of the hippocampus in the brain and the normalization of diversity in the intestinal microbiota," says researcher Anna Sancho-Balcells (UB-UBneuro-CIBERNED), first author of the study.
«From other studies – continues the expert – it was known that the sirtuin SIRT1 pathway is altered in preclinical models of stress and depression. However, it was still unknown to discover the mechanisms by which photobiomodulation exerts beneficial effects. "In our study we found that the SIRT1 pathway is the most altered physiological pathway in certain regions of the brain under conditions of chronic stress, and photobiomodulation has the ability to restore it."
In the digestive system, photobiomodulation would activate changes in the intestinal microbiota, effects that are more visible when it comes to double brain-gut stimulation compared to treatment of the intestine alone. As Professor Xavier Xifró, from the TargetsLab research group at the Faculty of Medicine of the University of Girona, explains, “the associated cellular mechanisms seem to be linked to the improvement of neuroinflammatory processes. Thus, the changes observed in the microbiota are strongly associated with some changes in neuroinflammation (for example, microgliosis and astrogliosis, which occur through the inflammation of specific cells of the nervous system).
Combined photobiomodulation in patients with depression
Photobiomodulation would emerge as a potential adjuvant treatment to be administered in coordination with pharmacological therapy in cases of severe depressive disorders. In future lines of research, the team wants to promote the design of clinical trials to verify the effectiveness of combined photobiomodulation in patients with depression.
'Photobiomodulation is likely to be particularly suitable in specific forms of depression, such as treatment-resistant depression. We also want to explore the relationship with neuroinflammation processes: this is one of the parameters best rescued after photobiomodulation, and treatment-resistant depression is closely associated with neuroinflammation," concludes the research team.
