Abstract
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.
Highlights
Our results showed that nicotinamide mononucleotide (NMN) administration increased brain NAD+ levels, prevented loss of SIRT1, and decreased acetylation of hippocampal proteins
A week after STZ administration, blood glucose levels were measured to make sure that the levels were above 300 mg/dL, nicotinamide mononucleotide (NMN) was administered subcutaneously at a dose of 100 mg/kg on alternate days for the 3 months
The intraperitoneal glucose tolerance test (n = 6) showed a significant increase in area under the curve (AUC) in Diabetic rats compared to Non-Diabetic rats and there was no significant difference in AUC between Diabetic and Diabetic + NMN rats (Table 1 and Figure S1), suggesting NMN did not affect glucose toxicity
Summary
There is increasing evidence that diabetes predisposes to cognitive decline leading to dementia in both animal models and humans [1]. Oxidative stress plays a central role in brain and neuronal damage in both clinical and experimental diabetes [7,11]. Oxidative damage to various brain regions contributes to development of long-term complications, morphological abnormalities, and memory impairment [13,14,15]. These oxidant radicals contribute to increased neuronal death through oxidation of proteins, DNA damage, and peroxidation of lipids [15]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
