810-nm Photobiomodulation Evokes Glutamate Release in Normal and Rotenone-Dysfunctional Cortical Nerve Terminals by Modulating Mitochondrial Energy Metabolism
The dysfunction of mitochondria, the primary source of cellular energy and producer of reactive oxygen species (ROS), is associated with brain aging and neurodegenerative diseases. Scientific evidence indicates that light in the visible and near-infrared spectrum can modulate mitochondrial activity,...
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2025-01-01
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| author | Silvia Ravera Elisa Farsetti Guido Maura Manuela Marcoli Matteo Bozzo Chiara Cervetto Andrea Amaroli |
| author_facet | Silvia Ravera Elisa Farsetti Guido Maura Manuela Marcoli Matteo Bozzo Chiara Cervetto Andrea Amaroli |
| author_sort | Silvia Ravera |
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| description | The dysfunction of mitochondria, the primary source of cellular energy and producer of reactive oxygen species (ROS), is associated with brain aging and neurodegenerative diseases. Scientific evidence indicates that light in the visible and near-infrared spectrum can modulate mitochondrial activity, a phenomenon known in medicine as photobiomodulation therapy (PBM-t). The beneficial effects of PBM-t on dementia and neurodegeneration have been reviewed in the literature. However, the molecular mechanisms underlying these findings have yet to be fully elucidated. This study investigates the mechanism behind dose-dependent glutamate release in nerve terminals after irradiation with 810 nm, 1 W for 60 s continuous, 1 cm<sup>2</sup>, 1 W/cm<sup>2</sup>, 60 J, 60 J/cm<sup>2</sup> (810 nm-1 W) or 810 nm, 0.1 W for 60 s continuous, 1 cm<sup>2</sup>, 0.1 W/cm<sup>2</sup>, 6 J, 6 J/cm<sup>2</sup> (810 nm-0.1 W), focusing on mitochondrial activities. The results show that PBM modulated the mitochondrial metabolism of cortical nerve terminals and supported a power-dependent increase in oxidative phosphorylation (OxPhos) activity when stimulated with pyruvate plus malate (P/M) or succinate (succ) as respiratory substrates. The PBM-induced increase in OxPhos was sensitive to adding rotenone (Complex I inhibitor) and antimycin A (Complex III inhibitor) when synaptosomes were stimulated with P/M, but only to antimycin A when stimulated with succ. This allowed us to observe that the glutamate efflux, disrupted in the presence of rotenone, was partially restored by PBM due to the increase in the OxPhos pathway led by Complex II. This evidence suggests that PBM, acting on mitochondria, could facilitate physiological communication within the neuron-astrocyte network through vesicular glutamate release, potentially regulating healthy brain function and brain dysfunction. |
| format | Article |
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| institution | Kabale University |
| issn | 2073-4409 |
| language | English |
| publishDate | 2025-01-01 |
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| spelling | doaj-art-cd3751ad67b44f96a90ecc07ce1107452025-01-24T13:26:33ZengMDPI AGCells2073-44092025-01-011426710.3390/cells14020067810-nm Photobiomodulation Evokes Glutamate Release in Normal and Rotenone-Dysfunctional Cortical Nerve Terminals by Modulating Mitochondrial Energy MetabolismSilvia Ravera0Elisa Farsetti1Guido Maura2Manuela Marcoli3Matteo Bozzo4Chiara Cervetto5Andrea Amaroli6Department of Experimental Medicine, University of Genova, 16132 Genova, ItalyDepartment of Pharmacy, Section of Pharmacology and Toxicology, University of Genova, 16148 Genova, ItalyDepartment of Earth, Environment and Life Sciences (DISTAV), University of Genova, 16132 Genova, ItalyDepartment of Earth, Environment and Life Sciences (DISTAV), University of Genova, 16132 Genova, ItalyDepartment of Earth, Environment and Life Sciences (DISTAV), University of Genova, 16132 Genova, ItalyIRCCS Ospedale Policlinico San Martino, 16132 Genova, ItalyInteruniversity Center for the Promotion of the 3Rs Principles in Teaching and Research (Centro 3R), 56122 Pisa, ItalyThe dysfunction of mitochondria, the primary source of cellular energy and producer of reactive oxygen species (ROS), is associated with brain aging and neurodegenerative diseases. Scientific evidence indicates that light in the visible and near-infrared spectrum can modulate mitochondrial activity, a phenomenon known in medicine as photobiomodulation therapy (PBM-t). The beneficial effects of PBM-t on dementia and neurodegeneration have been reviewed in the literature. However, the molecular mechanisms underlying these findings have yet to be fully elucidated. This study investigates the mechanism behind dose-dependent glutamate release in nerve terminals after irradiation with 810 nm, 1 W for 60 s continuous, 1 cm<sup>2</sup>, 1 W/cm<sup>2</sup>, 60 J, 60 J/cm<sup>2</sup> (810 nm-1 W) or 810 nm, 0.1 W for 60 s continuous, 1 cm<sup>2</sup>, 0.1 W/cm<sup>2</sup>, 6 J, 6 J/cm<sup>2</sup> (810 nm-0.1 W), focusing on mitochondrial activities. The results show that PBM modulated the mitochondrial metabolism of cortical nerve terminals and supported a power-dependent increase in oxidative phosphorylation (OxPhos) activity when stimulated with pyruvate plus malate (P/M) or succinate (succ) as respiratory substrates. The PBM-induced increase in OxPhos was sensitive to adding rotenone (Complex I inhibitor) and antimycin A (Complex III inhibitor) when synaptosomes were stimulated with P/M, but only to antimycin A when stimulated with succ. This allowed us to observe that the glutamate efflux, disrupted in the presence of rotenone, was partially restored by PBM due to the increase in the OxPhos pathway led by Complex II. This evidence suggests that PBM, acting on mitochondria, could facilitate physiological communication within the neuron-astrocyte network through vesicular glutamate release, potentially regulating healthy brain function and brain dysfunction.https://www.mdpi.com/2073-4409/14/2/67synaptosomesglutamatelow-level light therapylow-level laser therapyphototherapyoxidative phosphorylation |
| spellingShingle | Silvia Ravera Elisa Farsetti Guido Maura Manuela Marcoli Matteo Bozzo Chiara Cervetto Andrea Amaroli 810-nm Photobiomodulation Evokes Glutamate Release in Normal and Rotenone-Dysfunctional Cortical Nerve Terminals by Modulating Mitochondrial Energy Metabolism Cells synaptosomes glutamate low-level light therapy low-level laser therapy phototherapy oxidative phosphorylation |
| title | 810-nm Photobiomodulation Evokes Glutamate Release in Normal and Rotenone-Dysfunctional Cortical Nerve Terminals by Modulating Mitochondrial Energy Metabolism |
| title_full | 810-nm Photobiomodulation Evokes Glutamate Release in Normal and Rotenone-Dysfunctional Cortical Nerve Terminals by Modulating Mitochondrial Energy Metabolism |
| title_fullStr | 810-nm Photobiomodulation Evokes Glutamate Release in Normal and Rotenone-Dysfunctional Cortical Nerve Terminals by Modulating Mitochondrial Energy Metabolism |
| title_full_unstemmed | 810-nm Photobiomodulation Evokes Glutamate Release in Normal and Rotenone-Dysfunctional Cortical Nerve Terminals by Modulating Mitochondrial Energy Metabolism |
| title_short | 810-nm Photobiomodulation Evokes Glutamate Release in Normal and Rotenone-Dysfunctional Cortical Nerve Terminals by Modulating Mitochondrial Energy Metabolism |
| title_sort | 810 nm photobiomodulation evokes glutamate release in normal and rotenone dysfunctional cortical nerve terminals by modulating mitochondrial energy metabolism |
| topic | synaptosomes glutamate low-level light therapy low-level laser therapy phototherapy oxidative phosphorylation |
| url | https://www.mdpi.com/2073-4409/14/2/67 |
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