CONCLUSION

In this study, I demonstrated that LDHB KO mouse ameliorate ischemic neuronal cell death through the increase of PcomA size which was supported by the fact that VEGFA level is upregulated I cells. LDHB is an important enzyme in neuron for using lactate as energy source by converting lactate to pyruvate, since neuron uses lactate more than glucose as energy source. In normal condition, LDHB KO neuron cell appeared no difference, but in ischemic condition, the decreased neuronal cell death is shown. That means LDHB KO neuron cell may be less vulnerable to ischemia by preconditioning compared to LDHB WT. To elucidate preconditioning in LDHB KO neuron cells, further studies are needed.

VI. REFFERENCES

1. Albert Gjedde, Pierre Magistretti “Cellular Mechanisms of Brain Energy Metabolism” Neurosourgery. 2015

2. Barone FC, Knudsen DJ, Nelson AH, Feuerstein GZ, Willette RN. “Mouse Strain Differences in Susceptibility to Cerebral Ischemia Are Related to Cerebral Vascular Anatomy.” J Cereb Blood Flow Metab. 13(4):683-92. 1993.

3. Baxter P, Chen Y, Xu Y, Swanson RA. “Mitochondrial dysfunction induced by nuclear poly(ADP-ribose) polymerase-1: a treatable cause of cell death in stroke.” Transl Stroke Res. 5(1):136-44. 2014.

4. Bélanger M, Allaman I, Magistretti PJ “Brain Energy Metabolism: Focus on Astrocyte-Neuron Metabolic Cooperation” Cell Metab. 7;14(6):724-38. 2011.

5. Bittar PG, Charnay Y, Pellerin L, Bouras C, Magistretti PJ. “Selective distribution of lactate dehydrogenase isoenzymes in neurons and astrocytes of human brain.” J Cereb Blood Flow Metab. 16(6):1079-89. 1996.

6. Crawford RM, Budas GR, Jovanović S, Ranki HJ, Wilson TJ, Davies AM, Jovanović A. “M-LDH serves as a sarcolemmal K(ATP) channel subunit essential for cell protection against ischemia.” EMBO J. 1;21(15):3936-48.

2002.

7. Drent M, Cobben NA, Henderson RF, Wouters EF, van Dieijen-Visser M.

“Usefulness of lactate dehydrogenase and its isoenzymes as indicators of lung damage or inflammation.” Eur Respir J. 9(8):1736-42. 1996.

8. Falkowska A, Gutowska I, Goschorska M, Nowacki P, Chlubek D, Baranowska-Bosiacka I “Energy Metabolism of the Brain, Including the

Cooperation between Astrocytes and Neurons, Especially in the Context of Glycogen Metabolism" Int J Mol Sci. 29;16(11):25959-81. 2015.

9. Felipe A. Beltrán, Aníbal I. Acuña, María Paz Miró and Maite A. Castro

“Brain Energy Metabolism in Health and Disease”ISBN 978-953-51-0207-6.

2012.

10. Genc S, Kurnaz IA, Ozilgen M. “Astrocyte-neuron lactate shuttle may boost more ATP supply to the neuron under hypoxic conditions--in silico study supported by in vitro expression data.” BMC Syst Biol. 5:162. 2011.

11. Ito D, Tanaka K, Suzuki S, Dembo T, Fukuuchi Y. “Enhanced expression of Iba1, ionized calcium-binding adapter molecule 1, after transient focal cerebral ischemia in rat brain.” Stroke. 32(5):1208-15. 2001.

12. Johanna La¨hteenvuo, Anthony Rosenzweig “Effects of Aging on Angiogenesis” Circulation Research. 110:1252-1263. 2012.

13. Ke Q, Costa M. “Hypoxia-inducible factor-1 (HIF-1).” Mol Pharmacol.

70(5):1469-80. 2006.

14. Kitagawa K, Matsumoto M, Yang G, Mabuchi T, Yagita Y, Hori M, Yanagihara T. “Cerebral ischemia after bilateral carotid artery occlusion and intraluminal suture occlusion in mice: evaluation of the patency of the posterior communicating artery.” J Cereb Blood Flow Metab. 18(5):570-9.

1998.

15. Kyung-Ok Cho, Seul-Ki Kim, Young-Jin Cho, Ki-Wug Sung, and Seong Yun Kim. “A Simple Method for Predicting Hippocampal Neurodegeneration in a Mouse Model of Transient Global Forebrain Ischemia.” Korean J Physiol Pharmacol 10(4): 167-172. 2006.

16. Magistretti PJ, Allaman I “A Cellular Perspective on Brain Energy

Metabolism and Functional Imaging” Neuron. 20;86(4):883-901. 2015.

17. Magistretti PJ. “Neuron–glia metabolic coupling and plasticity” Exp Physiol.

96(4):407-10. 2011.

18. Mergenthaler P, Lindauer U, Dienel GA, Meisel A. “Sugar for the brain: the role of glucose in physiological and pathological brain function” Trends Neurosci. 36(10):587-97. 2013.

19. Michelle A. Puchowicz, Smruta S. Koppaka, Joseph C. LaManna. “Brain Metabolic Adaptations to Hypoxia” Metabolic Encephalopathy, 15-30, 2009 20. Newington JT, Harris RA, Cumming RC “Reevaluating Metabolism in

Alzheimer's Disease from the Perspective of the Astrocyte-Neuron Lactate Shuttle Model.” J Neurodegener Dis. 2013:234572. 2013.

21. Niizuma K, Endo H, Chan PH. “Oxidative stress and mitochondrial dysfunction as determinants of ischemic neuronal death and survival.” J Neurochem. 109 Suppl 1:133-8. 2009.

22. Pellerin L, Magistretti PJ. “Sweet sixteen for ANLS.” J Cereb Blood Flow Metab. 32(7):1152-66. 2012.

23. Porporato PE, Dhup S, Dadhich RK, Copetti T, Sonveaux P. “Anticancer targets in the glycolytic metabolism of tumors: a comprehensive review.”

Front Pharmacol. 25;2:49. 2011.

26. Seibenhener ML, Wooten MW. “Isolation and culture of hippocampal neurons

from prenatal mice.” J Vis Exp. 26;(65). pii: 3634. 2012.

27. Shah K, Desilva S, Abbruscato T. “The role of glucose transporters in brain disease: diabetes and Alzheimer’s Disease.” Int J Mol Sci. 3;13(10):12629-55.

2012.

28. Sharma PR, Jain S, Bamezai RN, Tiwari PK. “Utility of serum LDH isoforms in the assessment of mycobacterium tuberculosis induced pathology in TB patients of Sahariya tribe.” Indian J Clin Biochem. 25(1):57-63. 2010.

29. Suzuki A, Stern SA, Bozdagi O, Huntley GW, Walker RH, Magistretti PJ, Alberini CM. “Astrocyte-neuron lactate transport is required for long-term memory formation.” Cell. 4;144(5):810-23. 2011.

30. Tetsuya Mizuno “Neuron–microglia interactions in neuroinflammation”

neuroimmunology. 225–231. 2015.

31. Tulsulkar J, Shah ZA. “Ginkgo biloba prevents transient global ischemia-induced delayed hippocampal neuronal death through antioxidant and anti-inflammatory mechanism.” Neurochem Int. 62(2):189-97. 2013.

32. Zhang YB, Wang X, Meister EA, Gong KR, Yan SC, Lu GW, Ji XM, Shao G.

“The effects of CoCl2 on HIF-1α protein under experimental conditions of autoprogressive hypoxia using mouse models.” Int J Mol Sci. 8;15(6):10999-1012. 2014.

33. Zhou J, Schmid T, Frank R, Brüne B.” PI3K/Akt is required for heat shock proteins to protect hypoxia-inducible factor 1alpha from pVHL-independent degradation.” J Biol Chem. 2;279(14):13506-13. 2004.

- 국문요약 -

에서 뇌손상에 더 저항성이 있음을 알 수 있었다.

핵심어 : 젖산탈수소효소, 허혈성 스트레스, 신경세포 사멸, 혈관 표피 성장인자