Next Article in Journal
Spectroscopic Studies of R(+)-α-Lipoic Acid—Cyclodextrin Complexes
Next Article in Special Issue
Chrysin Protects against Focal Cerebral Ischemia/Reperfusion Injury in Mice through Attenuation of Oxidative Stress and Inflammation
Previous Article in Journal
Long Non-Coding RNAs: Critical Players in Hepatocellular Carcinoma
Previous Article in Special Issue
Long-Term Spinal Ventral Root Reimplantation, but not Bone Marrow Mononuclear Cell Treatment, Positively Influences Ultrastructural Synapse Recovery and Motor Axonal Regrowth
Article Menu
Issue 11 (November) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2014, 15(11), 20449-20468;

The Effects of NAD+ on Apoptotic Neuronal Death and Mitochondrial Biogenesis and Function after Glutamate Excitotoxicity

Dalton Cardiovascular Research Center, Department of Bioengineering, University of Missouri, Columbia, MO 65211, USA
Author to whom correspondence should be addressed.
Received: 25 August 2014 / Accepted: 3 November 2014 / Published: 7 November 2014
(This article belongs to the Special Issue Neuroprotective Strategies 2014)
Full-Text   |   PDF [2089 KB, uploaded 7 November 2014]   |  


NAD+ is an essential co-enzyme for cellular energy metabolism and is also involved as a substrate for many cellular enzymatic reactions. It has been shown that NAD+ has a beneficial effect on neuronal survival and brain injury in in vitro and in vivo ischemic models. However, the effect of NAD+ on mitochondrial biogenesis and function in ischemia has not been well investigated. In the present study, we used an in vitro glutamate excitotoxicity model of primary cultured cortical neurons to study the effect of NAD+ on apoptotic neuronal death and mitochondrial biogenesis and function. Our results show that supplementation of NAD+ could effectively reduce apoptotic neuronal death, and apoptotic inducing factor translocation after neurons were challenged with excitotoxic glutamate stimulation. Using different approaches including confocal imaging, mitochondrial DNA measurement and Western blot analysis of PGC-1 and NRF-1, we also found that NAD+ could significantly attenuate glutamate-induced mitochondrial fragmentation and the impairment of mitochondrial biogenesis. Furthermore, NAD+ treatment effectively inhibited mitochondrial membrane potential depolarization and NADH redistribution after excitotoxic glutamate stimulation. Taken together, our results demonstrated that NAD+ is capable of inhibiting apoptotic neuronal death after glutamate excitotoxicity via preserving mitochondrial biogenesis and integrity. Our findings provide insights into potential neuroprotective strategies in ischemic stroke. View Full-Text
Keywords: ischemic stroke; glutamate excitotoxicity; apoptosis; AIF; mitochondrial biogenesis ischemic stroke; glutamate excitotoxicity; apoptosis; AIF; mitochondrial biogenesis

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material


Share & Cite This Article

MDPI and ACS Style

Wang, X.; Li, H.; Ding, S. The Effects of NAD+ on Apoptotic Neuronal Death and Mitochondrial Biogenesis and Function after Glutamate Excitotoxicity. Int. J. Mol. Sci. 2014, 15, 20449-20468.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top