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Endogenous level of TIGAR in brain is associated with vulnerability of neurons to ischemic injury

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Abstract

In previous studies, we showed that TP53-induced glycolysis and apoptosis regulator (TIGAR) protects neurons against ischemic brain injury. In the present study, we investigated the developmental changes of TIGAR level in mouse brain and the correlation of TIGAR expression with the vulnerability of neurons to ischemic injury. We found that the TIGAR level was high in the embryonic stage, dropped at birth, partially recovered in the early postnatal period, and then continued to decline to a lower level in early adult and aged mice. The TIGAR expression was higher after ischemia/reperfusion in mouse brain 8 and 12 weeks after birth. Four-week-old mice had smaller infarct volumes, lower neurological scores, and lower mortality rates after ischemia than 8- and 12-week-old mice. TIGAR expression also increased in response to oxygen glucose deprivation (OGD)/reoxygenation insult or H2O2 treatment in cultured primary neurons from different embryonic stages (E16 and E20). The neurons cultured from the early embryonic period had a greater resistance to OGD and oxidative insult. Higher TIGAR levels correlated with higher pentose phosphate pathway activity and less oxidative stress. Older mice and more mature neurons had more severe DNA and mitochondrial damage than younger mice and less mature neurons in response to ischemia/reperfusion or OGD/reoxygenation insult. Supplementation of cultured neurons with nicotinamide adenine dinuclectide phosphate (NADPH) significantly reduced ischemic injury. These results suggest that TIGAR expression changes during development and its expression level may be correlated with the vulnerability of neurons to ischemic injury.

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Authors and Affiliations

  1. Department of Pharmacology and Laboratory of Aging and Nervous Diseases, Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, College of Pharmaceutical Science, Soochow University, Suzhou, 215123, China

    Lijuan Cao, Jieyu Chen, Mei Li, Yuan-Yuan Qin, Meiling Sun, Rui Sheng & Zheng-Hong Qin

  2. Institute of Pharmacology, Toxicology and Biochemical Pharmaceutics, Zhejiang University, Hangzhou, 310058, China

    Feng Han

  3. Department of Pharmacology and Laboratory of Molecular Neuropathology, Soochow University School of Pharmaceutical Science, Suzhou, 215123, China

    Guanghui Wang

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  1. Lijuan Cao
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  2. Jieyu Chen
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  3. Mei Li
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  4. Yuan-Yuan Qin
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  5. Meiling Sun
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  7. Feng Han
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  9. Zheng-Hong Qin
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Correspondence to Zheng-Hong Qin.

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Cao, L., Chen, J., Li, M. et al. Endogenous level of TIGAR in brain is associated with vulnerability of neurons to ischemic injury. Neurosci. Bull. 31, 527–540 (2015). https://doi.org/10.1007/s12264-015-1538-4

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  • DOI: https://doi.org/10.1007/s12264-015-1538-4

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