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Article

Nicotinamide Mononucleotide Administration Prevents Experimental Diabetes-Induced Cognitive Impairment and Loss of Hippocampal Neurons

1
Department of Neurology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
2
Veterans Affairs Medical Center, Baltimore, MD 21201, USA
3
Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA
4
Department of Anesthesiology; University of Maryland School of Medicine, Baltimore, MD 21201, USA
5
Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(11), 3756; https://doi.org/10.3390/ijms21113756
Received: 21 April 2020 / Revised: 18 May 2020 / Accepted: 19 May 2020 / Published: 26 May 2020
(This article belongs to the Special Issue Mitochondria-Targeted Approaches in Health and Disease)
Diabetes predisposes to cognitive decline leading to dementia and is associated with decreased brain NAD+ levels. This has triggered an intense interest in boosting nicotinamide adenine dinucleotide (NAD+) levels to prevent dementia. We tested if the administration of the precursor of NAD+, nicotinamide mononucleotide (NMN), can prevent diabetes-induced memory deficits. Diabetes was induced in Sprague-Dawley rats by the administration of streptozotocin (STZ). After 3 months of diabetes, hippocampal NAD+ levels were decreased (p = 0.011). In vivo localized high-resolution proton magnetic resonance spectroscopy (MRS) of the hippocampus showed an increase in the levels of glucose (p < 0.001), glutamate (p < 0.001), gamma aminobutyric acid (p = 0.018), myo-inositol (p = 0.018), and taurine (p < 0.001) and decreased levels of N-acetyl aspartate (p = 0.002) and glutathione (p < 0.001). There was a significant decrease in hippocampal CA1 neuronal volume (p < 0.001) and neuronal number (p < 0.001) in the Diabetic rats. Diabetic rats showed hippocampal related memory deficits. Intraperitoneal NMN (100 mg/kg) was given after induction and confirmation of diabetes and was provided on alternate days for 3 months. NMN increased brain NAD+ levels, normalized the levels of glutamate, taurine, N-acetyl aspartate (NAA), and glutathione. NMN-treatment prevented the loss of CA1 neurons and rescued the memory deficits despite having no significant effect on hyperglycemic or lipidemic control. In hippocampal protein extracts from Diabetic rats, SIRT1 and PGC-1α protein levels were decreased, and acetylation of proteins increased. NMN treatment prevented the diabetes-induced decrease in both SIRT1 and PGC-1α and promoted deacetylation of proteins. Our results indicate that NMN increased brain NAD+, activated the SIRT1 pathway, preserved mitochondrial oxidative phosphorylation (OXPHOS) function, prevented neuronal loss, and preserved cognition in Diabetic rats. View Full-Text
Keywords: NAD+; NMN; diabetes; dementia; cognitive impairment; mitochondria; SIRT1; PGC-1α; NEDD4-1 NAD+; NMN; diabetes; dementia; cognitive impairment; mitochondria; SIRT1; PGC-1α; NEDD4-1
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MDPI and ACS Style

Chandrasekaran, K.; Choi, J.; Arvas, M.I.; Salimian, M.; Singh, S.; Xu, S.; Gullapalli, R.P.; Kristian, T.; Russell, J.W. Nicotinamide Mononucleotide Administration Prevents Experimental Diabetes-Induced Cognitive Impairment and Loss of Hippocampal Neurons. Int. J. Mol. Sci. 2020, 21, 3756. https://doi.org/10.3390/ijms21113756

AMA Style

Chandrasekaran K, Choi J, Arvas MI, Salimian M, Singh S, Xu S, Gullapalli RP, Kristian T, Russell JW. Nicotinamide Mononucleotide Administration Prevents Experimental Diabetes-Induced Cognitive Impairment and Loss of Hippocampal Neurons. International Journal of Molecular Sciences. 2020; 21(11):3756. https://doi.org/10.3390/ijms21113756

Chicago/Turabian Style

Chandrasekaran, Krish, Joungil Choi, Muhammed I. Arvas, Mohammad Salimian, Sujal Singh, Su Xu, Rao P. Gullapalli, Tibor Kristian, and James W. Russell. 2020. "Nicotinamide Mononucleotide Administration Prevents Experimental Diabetes-Induced Cognitive Impairment and Loss of Hippocampal Neurons" International Journal of Molecular Sciences 21, no. 11: 3756. https://doi.org/10.3390/ijms21113756

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