NAD(+) administration decreases ischemic brain damage partially by blocking autophagy in a mouse model of brain ischemia.

Abstract

Nicotinamide adenine dinuleotide (NAD(+)) plays critical roles in multiple biological functions. Previous studies have indicated that NAD(+) treatment decreases oxidative stress-induced death of primary neurons and astrocytes. Intranasal administration of NAD(+) also reduces brain damage in a rat model of transient focal brain ischemia. However, the mechanisms underlying this protective effect remain unknown. In this study, we used a mouse model of brain ischemia to test our hypothesis that NAD(+) decreases ischemic brain damage partially by preventing autophagy. Adult male mice were subjected to transient middle cerebral artery occlusion (tMCAO) for 90min, and NAD(+) was administered intraperitoneally (i.p.) immediately after reperfusion started. We found that administration with 50mg/kg NAD(+) led to significant decreases in infarct size, edema formation, and neurological deficits at 48h after ischemia. NAD(+) administration also significantly decreased brain ischemia-induced autophagy in the cortex and hippocampus. We further found that prevention of autophagy by 3-methyladenine (3-MA), a selective autophagy inhibitor, significantly reduced ischemic brain damage, suggesting an important role of autophagy in the ischemic brain injury in our animal model. Collectively, our findings have suggested that NAD(+) administration decreases ischemic brain damage at least partially by blocking autophagy. This is the first suggested mechanism regarding the protective effects of NAD(+) in cerebral ischemia, which further highlights the promise of NAD(+) for treating brain ischemia.

• Authors: Chaobo Zheng, Jin Han, Weiliang Xia, Shengtao Shi, Jianrong Liu, Weihai Ying
• Journal: Neuroscience letters (Neurosci Lett) Vol. 512 Issue 2 Pg. 67-71 (Mar 23 2012) ISSN: 1872-7972 [Electronic] Ireland
• PMID: 22260797 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• NAD

Topics

• Animals
• Autophagy (drug effects)
• Brain Infarction (pathology)
• Brain Ischemia (drug therapy, pathology)
• Disease Models, Animal
• Male
• Mice
• NAD (therapeutic use)