NAD+ Precursors Reverse Experimental Diabetic Neuropathy in Mice
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Published:2024-01-16
Issue:2
Volume:25
Page:1102
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Chandrasekaran Krish1, Najimi Neda1, Sagi Avinash R.1, Yarlagadda Sushuma1, Salimian Mohammad1, Arvas Muhammed Ikbal1, Hedayat Ahmad F.1, Kevas Yanni1, Kadakia Anand1, Kristian Tibor23ORCID, Russell James W.134ORCID
Affiliation:
1. Department of Neurology, University of Maryland School of Medicine, Baltimore, MD 21201, USA 2. Department of Anesthesiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA 3. Veterans Affairs Medical Center, Baltimore, MD 21201, USA 4. CAMC Institute for Academic Medicine, 415 Morris Street Suite 300, Charleston, WV 25301, USA
Abstract
Abnormal NAD+ signaling has been implicated in axonal degeneration in diabetic peripheral neuropathy (DPN). We hypothesized that supplementing NAD+ precursors could alleviate DPN symptoms through increasing the NAD+ levels and activating the sirtuin-1 (SIRT1) protein. To test this, we exposed cultured Dorsal Root Ganglion neurons (DRGs) to Nicotinamide Riboside (NR) or Nicotinamide Mononucleotide (NMN), which increased the levels of NAD+, the SIRT1 protein, and the deacetylation activity that is associated with increased neurite growth. A SIRT1 inhibitor blocked the neurite growth induced via NR or NMN. We then induced neuropathy in C57BL6 mice with streptozotocin (STZ) or a high fat diet (HFD) and administered NR or NMN for two months. Both the STZ and HFD mice developed neuropathy, which was reversed through the NR or NMN administration: sensory function improved, nerve conduction velocities normalized, and intraepidermal nerve fibers were restored. The NAD+ levels and SIRT1 activity were reduced in the DRGs from diabetic mice but were preserved with the NR or NMN treatment. We also tested the effect of NR or NMN administration in mice that overexpress the SIRT1 protein in neurons (nSIRT1 OE) and found no additional benefit from the addition of the drug. These findings suggest that supplementing with NAD+ precursors or activating SIRT1 may be a promising treatment for DPN.
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
Reference79 articles.
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