Axonal Protection by Oral Nicotinamide Riboside Treatment with Upregulated AMPK Phosphorylation in a Rat Glaucomatous Degeneration Model
Nicotinamide riboside (NR), a precursor of nicotinamide adenine dinucleotide (NAD<sup>+</sup>), has been studied to support human health against metabolic stress, cardiovascular disease, and neurodegenerative disease. In the present study, we investigated the effects of oral NR on axonal...
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2023-08-01
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| Series: | Current Issues in Molecular Biology |
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| author | Ibuki Arizono Naoki Fujita Chihiro Tsukahara Kana Sase Reio Sekine Tatsuya Jujo Mizuki Otsubo Naoto Tokuda Yasushi Kitaoka |
| author_facet | Ibuki Arizono Naoki Fujita Chihiro Tsukahara Kana Sase Reio Sekine Tatsuya Jujo Mizuki Otsubo Naoto Tokuda Yasushi Kitaoka |
| author_sort | Ibuki Arizono |
| collection | DOAJ |
| description | Nicotinamide riboside (NR), a precursor of nicotinamide adenine dinucleotide (NAD<sup>+</sup>), has been studied to support human health against metabolic stress, cardiovascular disease, and neurodegenerative disease. In the present study, we investigated the effects of oral NR on axonal damage in a rat ocular hypertension model. Intraocular pressure (IOP) elevation was induced by laser irradiation and then the rats received oral NR of 1000 mg/kg/day daily. IOP elevation was seen 7, 14, and 21 days after laser irradiation compared with the controls. We confirmed that oral NR administration significantly increased NAD<sup>+</sup> levels in the retina. After 3-week oral administration of NR, morphometric analysis of optic nerve cross-sections showed that the number of axons was protected compared with that in the untreated ocular hypertension group. Oral NR administration significantly prevented retinal ganglion cell (RGC) fiber loss in retinal flat mounts, as shown by neurofilament immunostaining. Immunoblotting samples from the optic nerves showed that oral NR administration augmented the phosphorylated adenosine monophosphate-activated protein kinase (p-AMPK) level in rats with and without ocular hypertension induction. Immunohistochemical analysis showed that some p-AMPK-immunopositive fibers were colocalized with neurofilament immunoreactivity in the control group, and oral NR administration enhanced p-AMPK immunopositivity. Our findings suggest that oral NR administration protects against glaucomatous RGC axonal degeneration with the possible upregulation of p-AMPK. |
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| last_indexed | 2024-03-10T22:54:48Z |
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| series | Current Issues in Molecular Biology |
| spelling | doaj.art-00457c21ff0c4bf1bc0b4cb1d03a95e62023-11-19T10:04:44ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452023-08-014597097710910.3390/cimb45090449Axonal Protection by Oral Nicotinamide Riboside Treatment with Upregulated AMPK Phosphorylation in a Rat Glaucomatous Degeneration ModelIbuki Arizono0Naoki Fujita1Chihiro Tsukahara2Kana Sase3Reio Sekine4Tatsuya Jujo5Mizuki Otsubo6Naoto Tokuda7Yasushi Kitaoka8Department of Molecular Neuroscience, St. Marianna University Graduate School of Medicine, Kawasaki 216-8511, JapanDepartment of Ophthalmology, St. Marianna University School of Medicine, Kawasaki 216-8511, JapanDepartment of Ophthalmology, St. Marianna University School of Medicine, Kawasaki 216-8511, JapanDepartment of Ophthalmology, St. Marianna University School of Medicine, Kawasaki 216-8511, JapanDepartment of Ophthalmology, St. Marianna University School of Medicine, Kawasaki 216-8511, JapanDepartment of Ophthalmology, St. Marianna University School of Medicine, Kawasaki 216-8511, JapanDepartment of Molecular Neuroscience, St. Marianna University Graduate School of Medicine, Kawasaki 216-8511, JapanDepartment of Ophthalmology, St. Marianna University School of Medicine, Kawasaki 216-8511, JapanDepartment of Molecular Neuroscience, St. Marianna University Graduate School of Medicine, Kawasaki 216-8511, JapanNicotinamide riboside (NR), a precursor of nicotinamide adenine dinucleotide (NAD<sup>+</sup>), has been studied to support human health against metabolic stress, cardiovascular disease, and neurodegenerative disease. In the present study, we investigated the effects of oral NR on axonal damage in a rat ocular hypertension model. Intraocular pressure (IOP) elevation was induced by laser irradiation and then the rats received oral NR of 1000 mg/kg/day daily. IOP elevation was seen 7, 14, and 21 days after laser irradiation compared with the controls. We confirmed that oral NR administration significantly increased NAD<sup>+</sup> levels in the retina. After 3-week oral administration of NR, morphometric analysis of optic nerve cross-sections showed that the number of axons was protected compared with that in the untreated ocular hypertension group. Oral NR administration significantly prevented retinal ganglion cell (RGC) fiber loss in retinal flat mounts, as shown by neurofilament immunostaining. Immunoblotting samples from the optic nerves showed that oral NR administration augmented the phosphorylated adenosine monophosphate-activated protein kinase (p-AMPK) level in rats with and without ocular hypertension induction. Immunohistochemical analysis showed that some p-AMPK-immunopositive fibers were colocalized with neurofilament immunoreactivity in the control group, and oral NR administration enhanced p-AMPK immunopositivity. Our findings suggest that oral NR administration protects against glaucomatous RGC axonal degeneration with the possible upregulation of p-AMPK.https://www.mdpi.com/1467-3045/45/9/449nicotinamide ribosidep-AMPKglaucomaoptic nerveRGC |
| spellingShingle | Ibuki Arizono Naoki Fujita Chihiro Tsukahara Kana Sase Reio Sekine Tatsuya Jujo Mizuki Otsubo Naoto Tokuda Yasushi Kitaoka Axonal Protection by Oral Nicotinamide Riboside Treatment with Upregulated AMPK Phosphorylation in a Rat Glaucomatous Degeneration Model Current Issues in Molecular Biology nicotinamide riboside p-AMPK glaucoma optic nerve RGC |
| title | Axonal Protection by Oral Nicotinamide Riboside Treatment with Upregulated AMPK Phosphorylation in a Rat Glaucomatous Degeneration Model |
| title_full | Axonal Protection by Oral Nicotinamide Riboside Treatment with Upregulated AMPK Phosphorylation in a Rat Glaucomatous Degeneration Model |
| title_fullStr | Axonal Protection by Oral Nicotinamide Riboside Treatment with Upregulated AMPK Phosphorylation in a Rat Glaucomatous Degeneration Model |
| title_full_unstemmed | Axonal Protection by Oral Nicotinamide Riboside Treatment with Upregulated AMPK Phosphorylation in a Rat Glaucomatous Degeneration Model |
| title_short | Axonal Protection by Oral Nicotinamide Riboside Treatment with Upregulated AMPK Phosphorylation in a Rat Glaucomatous Degeneration Model |
| title_sort | axonal protection by oral nicotinamide riboside treatment with upregulated ampk phosphorylation in a rat glaucomatous degeneration model |
| topic | nicotinamide riboside p-AMPK glaucoma optic nerve RGC |
| url | https://www.mdpi.com/1467-3045/45/9/449 |
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