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Background: Chronic stress is an important risk factor for the development of major depressive disorder (MDD). Recent studies have shown microbiome dysbiosis as one of the pathogenic mechanisms associated with MDD. Thus, it is important to find novel non-pharmacological therapeutic strategies that can modulate gut microbiota and brain activity. One such strategy is photobiomodulation (PBM), which involves the non-invasive use of light., Objective/hypothesis: Brain-gut PBM could have a synergistic beneficial effect on the alterations induced by chronic stress., Methods: We employed the chronic unpredictable mild stress (CUMS) protocol to induce a depressive-like state in mice. Subsequently, we administered brain-gut PBM for 6 min per day over a period of 3 weeks. Following PBM treatment, we examined behavioral, structural, molecular, and cellular alterations induced by CUMS., Results: We observed that the CUMS protocol induces profound behavioral alterations and an increase of sirtuin1 (Sirt1) levels in the hippocampus. We then combined the stress protocol with PBM and found that tissue-combined PBM was able to rescue cognitive alterations induced by CUMS. This rescue was accompanied by a restoration of hippocampal Sirt1 levels, prevention of spine density loss in the CA1 of the hippocampus, and the modulation of the gut microbiome. PBM was also effective in reducing neuroinflammation and modulating the morphology of Iba1-positive microglia., Limitations: The molecular mechanisms behind the beneficial effects of tissue-combined PBM are not fully understood., Conclusions: Our results suggest that non-invasive photobiomodulation of both the brain and the gut microbiome could be beneficial in the context of stress-induced MDD., Competing Interests: Declaration of competing interest GB is an employee of REGEnLIFE and owns equity. JT is a consultant for REGEnLIFE. The rest of the authors declare no competing financial interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The evidence of brain-gut interconnections in Alzheimer's disease (AD) opens novel avenues for the treatment of a pathology for which no definitive treatment exists. Gut microbiota and bacterial translocation may produce peripheral inflammation and immune modulation, contributing to brain amyloidosis, neurodegeneration, and cognitive deficits in AD. The gut microbiota can be used as a potential therapeutic target in AD. In particular, photobiomodulation (PBM) can affect the interaction between the microbiota and the immune system, providing a potential explanation for its restorative properties in AD-associated dysbiosis. PBM is a safe, non-invasive, non-ionizing, and non-thermal therapy that uses red or near-infrared light to stimulate the cytochrome c oxidase (CCO, complex IV), the terminal enzyme of the mitochondrial electron transport chain, resulting in adenosine triphosphate synthesis. The association of the direct application of PBM to the head with an abscopal and a systemic treatment through simultaneous application to the abdomen provides an innovative therapeutic approach to AD by targeting various components of this highly complex pathology. As a hypothesis, PBM might have a significant role in the therapeutic options available for the treatment of AD., Competing Interests: GB is an employee of REGEnLIFE and owns equity in the company. FJR is the director of FR Consulting. BL and CR are employees of Vaiomer. BL is a shareholder of Vaiomer. The authors declare no conflict of interest and the writing is not influenced by this relationship., (© 2024 The Author(s). Published by IMR Press.)

Recently, novel non-pharmacological interventions, such as photobiomodulation (PBM) therapy, have shown promise for the treatment of Alzheimer's disease (AD). This article outlines the translation from the preclinical to clinical stages of an innovative brain-gut PBM therapy in a mouse model of AD, a pilot clinical trial involving mild-to-moderate AD patients, and a continuing pivotal clinical trial with a similar patient population. In a mouse model of AD (Aβ25-35), daily application of brain-gut PBM therapy to both the head and the abdomen produced a neuroprotective effect against the neurotoxic effects of an Aβ25-35 peptide injection by normalizing all the modified behavioral and biochemical parameters. The pilot clinical trial to evaluate brain-gut PBM therapy demonstrated the tolerability and feasibility of the novel PBM-based treatment for mild-to-moderate AD patients. Compared to the sham patients, the PBM-treated patients had lower Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) comprehension sub-scores, higher forward verbal spans, and lower Trail Making Test (TMT) Part B (TMT-B) execution times, which suggest an improvement in cognitive functions. This pilot study provided important information for the design of a novel pivotal clinical trial, currently in progress, to assess the efficacy of brain-gut PBM therapy in a larger sample of AD patients. This pivotal clinical trial could demonstrate that brain-gut PBM therapy is a safe, well-tolerated, and efficient disease-modifying treatment for mild-to-moderate AD patients and that it has medical and economic benefits., Competing Interests: Guillaume Blivet is an employee of REGEnLIFE and owns equity. Jacques Touchon is a consultant for REGEnLIFE. François J. Roman is the director of FR Consulting. The authors declare no conflict of interest and the writing were not influenced by this relationship., (© 2024 The Author(s). Published by IMR Press.)

Quantitative phase microscopies (QPMs) enable label-free, non-invasive observation of living cells in culture, for arbitrarily long periods of time. One of the main benefits of QPMs compared with fluorescence microscopy is the possibility to measure the dry mass of individual cells or organelles. While QPM dry mass measurements on neural cells have been reported this last decade, dry mass measurements on their neurites has been very little addressed. Because neurites are tenuous objects, they are difficult to precisely characterize and segment using most QPMs. In this article, we use cross-grating wavefront microscopy (CGM), a high-resolution wavefront imaging technique, to measure the dry mass of individual neurites of primary neurons in vitro . CGM is based on the simple association of a cross-grating positioned in front of a camera, and can detect wavefront distortions smaller than a hydrogen atom (∼0.1 nm). In this article, an algorithm for dry-mass measurement of neurites from CGM images is detailed and provided. With objects as small as neurites, we highlight the importance of dealing with the diffraction rings for proper image segmentation and accurate biomass measurements. The high precision of the measurements we obtain using CGM and this semi-manual algorithm enabled us to detect periodic oscillations of neurites never observed before, demonstrating the sufficient degree of accuracy of CGM to capture the cell dynamics at the single neurite level, with a typical precision of 2%, i.e., 0.08 pg in most cases, down to a few fg for the smallest objects., Competing Interests: The authors declare no conflicts of interest., (© 2022 Optica Publishing Group under the terms of the Optica Open Access Publishing Agreement.)

Background: Recent innovative non-pharmacological interventions and neurostimulation devices have shown potential for application in the treatment of Alzheimer's disease (AD). These include photobiomodulation (PBM) therapy., Objective: This pilot study assesses the safety, compliance with, and efficacy of a brain-gut PBM therapy for mild-to-moderate AD patients., Methods: This double-blind, randomized, monocentric sham-controlled study started in 2018 and ended prematurely in 2020 due to the COVID-19 pandemic. Fifty-three mild-to-moderate AD patients were randomized, 27 in the PBM group and 26 in the sham group. All patients had 40 treatment sessions lasting 25 min each over 8 weeks and were followed for 4 weeks afterwards. Compliance with the treatment was recorded. Safety was assessed by recording adverse events (AEs), and efficacy was evaluated using neuropsychological tests., Results: The PBM therapy proved to be safe in regard to the number of recorded AEs (44% of the patients), which were balanced between the PBM and sham groups. AEs were mainly mild, and no serious AEs were reported. The majority of the patients (92.5%) were highly compliant, which confirms the feasibility of the PBM treatment. Compared to the sham patients, the PBM patients showed lower ADAS-Cog comprehension subscores, higher forward verbal spans, and lower TMT-B execution times, which suggests an improvement in cognitive functions., Conclusion: This study demonstrates the tolerability of and patient compliance with a PBM-based treatment for mild-to-moderate AD patients. It highlights encouraging efficacy trends and provides insights for the design of the next phase trial in a larger AD patient sample.

Introduction: Photobiomodulation was assessed as a novel treatment of Alzheimer's disease (AD) by the use of a new device RGn500 combining photonic and magnetic emissions in a mouse model of AD., Methods: Following the injection of amyloid β 25-35 peptide in male Swiss mice, RGn500 was applied once a day for 7 days either on the top of the head or the center of abdomen or both., Results: RGn500 daily application for 10 min produced a neuroprotective effect on the neurotoxic effects of amyloid β 25-35 peptide injection when this type of photobiomodulation was applied both on the head and on the abdomen. Protection was demonstrated by memory restoration and on the normalization of key markers of AD (amyloid β 1-42, pTau), oxidative stress (lipid peroxidation), apoptosis (Bax/Bcl2) and neuroinflammation., Discussion: RGn500 displays therapeutic efficacy similar to other pharmacological approaches evaluated in this model of AD.