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NAMPT INHIBITOR AND METABOLITE PROTECT MOUSE BRAIN FROM CRYOINJURY THROUGH DISTINCT MECHANISMS
Zhang, X. -Q.1; Lu, J. -T.1; Jiang, W. -X.2,3; Lu, Y. -B.1; Wu, M.4; Wei, E. -Q.1; Zhang, W. -P.1; Tang, C.2,3
2015-04-16
Source PublicationNEUROSCIENCE
Volume291Pages:230-240
SubtypeArticle
AbstractNicotinamide phosphoribosyltransferase (NAMPT) is the key enzyme in the biosynthesis of nicotinamide adenine dinucleotide (NAD). In the brain, NAMPT is primarily expressed in neurons and can prevent neuronal degeneration. NAMPT is also highly expressed in inflammatory cells, and is responsible for their activation. Since inflammation following traumatic brain injury enhances neuronal damage, we assessed the effects of nicotinamide mononucleotide (NMN), the direct NAMPT metabolite, and FK866, a potent NAMPT inhibitor, on brain injury in a cryoinjury mouse model. Twenty-four hours after brain cryoinjury, the density of neuron and the level of NAD decreased. Both NMN and FK866 alleviated the neuronal loss and decreased the lesion volume. NMN prevented the cryoinjury-induced decrease of NAD level, and FK866 decreased it further. On day 14 after cryoinjury, further neuronal loss occurred, astrocytes and Iba1-positive macrophage/microglia activated, and the NAD level increased. At this time-point, NAMPT expression was strongly induced in Iba1-positive macrophages/microglia in the lesion core. NMN and FK866 also alleviated the neuronal loss and decreased the lesion volume. In addition, FK866 significantly attenuated the activation of astrocytes and Iba1-positive macrophages/microglia, and decreased the NAD, while NMN had no such effects. Taken together, both FK866 and NMN attenuate traumatic brain injury. However, FK866 acts via the inhibition of the NAMPT activity in inflammatory cells resulting in the inhibition of inflammation, whereas NMN is effective via replenishing NAD. (C) 2015 IBRO. Published by Elsevier Ltd. All rights reserved.
KeywordNampt Fk866 Nmn Nad Cryoinjury Brain Injury
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
DOI10.1016/j.neuroscience.2015.02.007
WOS KeywordCOLONY-ENHANCING FACTOR ; NICOTINAMIDE PHOSPHORIBOSYLTRANSFERASE ; CEREBRAL-ISCHEMIA ; NAD BIOSYNTHESIS ; ENZYMATIC-ACTIVITY ; IN-VITRO ; INJURY ; NEUROPROTECTION ; INFLAMMATION ; PATHWAY
Indexed BySCI
Language英语
WOS Research AreaNeurosciences & Neurology
WOS SubjectNeurosciences
WOS IDWOS:000351303100020
Citation statistics
Cited Times:6[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.wipm.ac.cn/handle/112942/1050
Collection磁共振应用研究部
Affiliation1.Zhejiang Univ, Sch Med, Dept Pharmacol, Hangzhou 310058, Zhejiang, Peoples R China
2.Chinese Acad Sci, Natl Ctr Magnet Resonance Wuhan, Key Lab Magnet Resonance Biol Syst, State Key Lab Magnet Resonance & Atom Mol Phys, Wuhan 430071, Hubei Province, Peoples R China
3.Chinese Acad Sci, Wuhan Inst Phys & Math, Wuhan 430071, Hubei Province, Peoples R China
4.Zhejiang Univ, Affiliated Hosp 2, Sch Med, Dept Cardiothorac Surg, Hangzhou 310058, Zhejiang, Peoples R China
Recommended Citation
GB/T 7714
Zhang, X. -Q.,Lu, J. -T.,Jiang, W. -X.,et al. NAMPT INHIBITOR AND METABOLITE PROTECT MOUSE BRAIN FROM CRYOINJURY THROUGH DISTINCT MECHANISMS[J]. NEUROSCIENCE,2015,291:230-240.
APA Zhang, X. -Q..,Lu, J. -T..,Jiang, W. -X..,Lu, Y. -B..,Wu, M..,...&Tang, C..(2015).NAMPT INHIBITOR AND METABOLITE PROTECT MOUSE BRAIN FROM CRYOINJURY THROUGH DISTINCT MECHANISMS.NEUROSCIENCE,291,230-240.
MLA Zhang, X. -Q.,et al."NAMPT INHIBITOR AND METABOLITE PROTECT MOUSE BRAIN FROM CRYOINJURY THROUGH DISTINCT MECHANISMS".NEUROSCIENCE 291(2015):230-240.
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