Abstract
Photobiomodulation therapy has become the focus of medical research in many areas such as Alzheimer’s disease (AD), because of its modulatory effect on cellular processes through light energy absorption via photoreceptors/chromophores located in the mitochondria. However, there are still many questions around the underlying mechanisms. This study was carried out to unravel whether the function-structure of ATP-sensitive mitoBKCa channels, as crucial components for maintenance of mitochondrial homeostasis, can be altered subsequent to light therapy in AD. Induction of Aβ neurotoxicity in male Wistar rats was done by intracerebroventricular injection of Aβ1-42. After a week, light-treated rats were exposed to 40-Hz white light LEDs, 15 min for 7 days. Electrophysiological properties of mitoBKCa channel were investigated using a channel incorporated into the bilayer lipid membrane, and mitoBKCa-β2 subunit expression was determined using western blot analysis in Aβ-induced toxicity and light-treated rats. Our results describe that conductance and open probability (Po) of mitoBKCa channel decreased significantly and was accompanied by a Po curve rightward shift in mitochondrial preparation in Aβ-induced toxicity rats. We also showed a significant reduction in expression of mitoBKCa-β2 subunit, which is partly responsible for a leftward shift in BKCa Po curve in low calcium status. Interestingly, we provided evidence of a significant improvement in channel conductance and Po after light therapy. We also found that light therapy improved mitoBKCa-β2 subunit expression, increasing it close to saline group. The current study explains a light therapy improvement in brain mitoBKCa channel function in the Aβ-induced neurotoxicity rat model, an effect that can be linked to increased expression of β2 subunit.
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Data and material are available upon request to the corresponding author.
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Acknowledgements
We thank Neurophysiology Research Center of Shahid Beheshti University of Medical Sciences for financial support.
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This work was supported by a grant from the Neurophysiology Research Center of Shahid Beheshti University of Medical Sciences.
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Afsaneh Eliassi convinced and designed the overall study. Maryam Nazari and Adele Jafari performed all the experiments. Maryam Nazari, Adele Jafari, Nihad Torabi, and Javad Fahanik-babaei assisted in data analysis. Taha Vajed-Samiei and Rasoul Ghasemi contributed reagents/materials/analysis tools and software. Maryam Nazari and Afsaneh Eliassi wrote the paper. All authors read and approved the final manuscript.
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All experiments were conducted according to the Guide for Care and Use of Laboratory Animals (National Institutes of Health Publication No. 80–23, revised 1996). Additionally, all procedures were reviewed and confirmed by the Research and Ethics Committee of Shahid Beheshti University of Medical Sciences (IR.SBMU.MSP.REC.1396.614).
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Highlights
• Brain ATP-sensitivemitoBKCa channel activity is decreased in Aβ toxicity model.
• Decreased mitoBKCa channel activity is partly linked to the expression of mitoBKCa β2 subunit.
• 40Hz white light therapy modifies both the structure and function of mitoBKCa channel in Aβ toxicity rats.
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Nazari, M., Jafari, A., Torabi, N. et al. The Effect of 40-Hz White LED Therapy on Structure–Function of Brain Mitochondrial ATP-Sensitive Ca-Activated Large-Conductance Potassium Channel in Amyloid Beta Toxicity. Neurotox Res 40, 1380–1392 (2022). https://doi.org/10.1007/s12640-022-00565-9
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DOI: https://doi.org/10.1007/s12640-022-00565-9