REFFERENCES

1. Allaman, I., M. Belanger and P. J. Magistretti (2015). "Methylglyoxal, the dark side of glycolysis." Front Neurosci 9: 23.

2. Attwell, D. and S. B. Laughlin (2001). "An energy budget for signaling in the grey matter of the brain." J Cereb Blood Flow Metab 21(10): 1133-1145.

3. Barnes, J. N. (2015). "Exercise, cognitive function, and aging." Adv Physiol Educ 39(2): 55-62.

4. Belanger, M., I. Allaman and P. J. Magistretti (2011). "Brain energy metabolism: focus on astrocyte-neuron metabolic cooperation." Cell Metab 14(6): 724-738.

5. Belanger, M., J. Yang, J. M. Petit, T. Laroche, P. J. Magistretti and I. Allaman (2011). "Role of the glyoxalase system in astrocyte-mediated neuroprotection." J Neurosci 31(50): 18338-18352.

6. Bittar, P. G., Y. Charnay, L. Pellerin, C. Bouras and P. J. Magistretti (1996).

"Selective distribution of lactate dehydrogenase isoenzymes in neurons and astrocytes of human brain." J Cereb Blood Flow Metab 16(6): 1079-1089.

7. Bolanos JP, Almeida A, Moncada S (2010). "Glycolysis: a bioenergitic or a survival pathway?" Trends Biochem Sci 35(3):145-9.

8. Deitmer, J. W., S. M. Theparambil, I. Ruminot and H. M. Becker (2017).

"Our hungry brain: Which role do glial cells plays for the energy supply?"

Neuroforum 23(1): A1-A8

9. Dias, C., C. F. Lourenco, E. Ferreiro, R. M. Barbosa, J. Laranjinha and A.

Ledo (2016). "Age-dependent changes in the glutamate-nitric oxide pathway in the hippocampus of the triple transgenic model of Alzheimer's disease:

implications for neurometabolic regulation." Neurobiol Aging 46: 84-95.

10. Ding, F., J. Yao, J. R. Rettberg, S. Chen and R. D. Brinton (2013). "Early decline in glucose transport and metabolism precedes shift to ketogenic

３３

system in female aging and Alzheimer's mouse brain: implication for bioenergetic intervention." PLoS One 8(11): e79977.

11. Erbsloh, F., A. Bernsmeier and H. Hillesheim (1958). "[The glucose consumption of the brain & its dependence on the liver]." Arch Psychiatr Nervenkr Z Gesamte Neurol Psychiatr 196(6): 611-626.

12. Fernandez-Fernandez, S., A. Almeida and J. P. Bolanos (2012).

"Antioxidant and bioenergetic coupling between neurons and astrocytes."

Biochem J 443(1): 3-11.

13. Garaschuk, O., H. M. Semchyshyn and V. I. Lushchak (2018). "Healthy brain aging: Interplay between reactive species, inflammation and energy supply." Ageing Res Rev 43: 26-45.

14. Hamezah, H. S., L. W. Durani, N. F. Ibrahim, D. Yanagisawa, T. Kato, A.

Shiino, S. Tanaka, H. A. Damanhuri, W. Z. W. Ngah and I. Tooyama (2017).

"Volumetric changes in the aging rat brain and its impact on cognitive and locomotor functions." Exp Gerontol 99: 69-79.

15. Harman, D. (1956). "Aging: a theory based on free radical and radiation chemistry." J Gerontol 11(3): 298-300.

16. Harris, R. A., L. Tindale, A. Lone, O. Singh, S. L. Macauley, M. Stanley, D.

M. Holtzman, R. Bartha and R. C. Cumming (2016). "Aerobic Glycolysis in the Frontal Cortex Correlates with Memory Performance in Wild-Type Mice But Not the APP/PS1 Mouse Model of Cerebral Amyloidosis." J Neurosci 36(6): 1871-1878.

17. Kim, J. H., E. L. Kim, Y. K. Lee, C. B. Park, B. W. Kim, H. J. Wang, C. H.

Yoon, S. J. Lee and G. Yoon (2011). "Decreased lactate dehydrogenase B expression enhances claudin 1-mediated hepatoma cell invasiveness via mitochondrial defects." Exp Cell Res 317(8): 1108-1118.

18. Larsson, N. G. (2010). "Somatic mitochondrial DNA mutations in mammalian aging." Annu Rev Biochem 79: 683-706.

３４

19. Lopes-Cardozo, M., O. M. Larsson and A. Schousboe (1986). "Acetoacetate and glucose as lipid precursors and energy substrates in primary cultures of astrocytes and neurons from mouse cerebral cortex." J Neurochem 46(3):

773-778.

20. Magistretti, P. J. and I. Allaman (2015). "A cellular perspective on brain energy metabolism and functional imaging." Neuron 86(4): 883-901.

21. Mergenthaler, P., U. Lindauer, G. A. Dienel and A. Meisel (2013). "Sugar for the brain: the role of glucose in physiological and pathological brain function." Trends Neurosci 36(10): 587-597.

22. Molina, D. K. and V. J. DiMaio (2012). "Normal organ weights in men: part II-the brain, lungs, liver, spleen, and kidneys." Am J Forensic Med Pathol 33(4): 368-372.

23. Newington, J. T., R. A. Harris and R. C. Cumming (2013). "Reevaluating Metabolism in Alzheimer's Disease from the Perspective of the Astrocyte-Neuron Lactate Shuttle Model." J Neurodegener Dis 2013: 234572.

24. Newman, L. A., D. L. Korol and P. E. Gold (2011). "Lactate produced by glycogenolysis in astrocytes regulates memory processing." PLoS One 6(12):

e28427.

25. Ojo, J. O., P. Rezaie, P. L. Gabbott and M. G. Stewart (2015). "Impact of age-related neuroglial cell responses on hippocampal deterioration." Front Aging Neurosci 7: 57.

26. Ooigawa, H., H. Nawashiro, S. Fukui, N. Otani, A. Osumi, T. Toyooka and K. Shima (2006). "The fate of Nissl-stained dark neurons following traumatic brain injury in rats: difference between neocortex and hippocampus regarding survival rate." Acta Neuropathol 112(4): 471-481.

27. Owen, Oliver E (2005). “Ketone bodies as a fuel for the brain during starvation." Biochemistry and molecular biology eoucation 33(4): 246-251 28. Pellerin, L. and P. J. Magistretti (1994). "Glutamate uptake into astrocytes

３５

stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization." Proc Natl Acad Sci U S A 91(22): 10625-10629.

29. Porporato, P. E., S. Dhup, R. K. Dadhich, T. Copetti and P. Sonveaux (2011).

"Anticancer targets in the glycolytic metabolism of tumors: a comprehensive review." Front Pharmacol 2: 49.

30. Prince, M., R. Bryce, E. Albanese, A. Wimo, W. Ribeiro and C. P. Ferri (2013). "The global prevalence of dementia: a systematic review and metaanalysis." Alzheimers Dement 9(1): 63-75.e62.

31. Ross, J. M., J. Oberg, S. Brene, G. Coppotelli, M. Terzioglu, K. Pernold, M.

Goiny, R. Sitnikov, J. Kehr, A. Trifunovic, N. G. Larsson, B. J. Hoffer and L. Olson (2010). "High brain lactate is a hallmark of aging and caused by a shift in the lactate dehydrogenase A/B ratio." Proc Natl Acad Sci U S A 107(46): 20087-20092.

32. Sharma, P. R., S. Jain, R. N. Bamezai and P. K. Tiwari (2010). "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.

33. Steinman, M. Q., V. Gao and C. M. Alberini (2016). "The Role of Lactate-Mediated Metabolic Coupling between Astrocytes and Neurons in Long-Term Memory Formation." Front Integr Neurosci 10: 10.

34. Stranahan, A. M., N. T. Jiam, A. M. Spiegel and M. Gallagher (2012).

"Aging reduces total neuron number in the dorsal component of the rodent prefrontal cortex." J Comp Neurol 520(6): 1318-1326.

35. Villena, A., F. Diaz, V. Requena, I. Chavarria, F. Rius and I. Perez de Vargas (1997). "Quantitative morphological changes in neurons from the dorsal lateral geniculate nucleus of young and old rats." Anat Rec 248(1): 137-141.

36. Yao, J., R. T. Hamilton, E. Cadenas and R. D. Brinton (2010). "Decline in mitochondrial bioenergetics and shift to ketogenic profile in brain during

３６

reproductive senescence." Biochim Biophys Acta 1800(10): 1121-1126.

37. Yao, J., R. W. Irwin, L. Zhao, J. Nilsen, R. T. Hamilton and R. D. Brinton (2009). "Mitochondrial bioenergetic deficit precedes Alzheimer's pathology in female mouse model of Alzheimer's disease." Proc Natl Acad Sci U S A 106(34): 14670-14675.

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aspartate (NAA) 비율의 비율이 증가함을 나타냈다.

결론을 말하여 나이든 LDHB KO 마우스에서는 lactate의 증가와 활성 산소 종의 증가로 인해 신경세포의 형태변화 및 행동 저하를 야기하는 것으로 나타났다.

핵심어: 젖산 탈수소 효소 B, knock-out 마우스, 젖산, 활성 산소 종, 신경세 포, 성상세포