Pyruvate prevents the development of age-dependent cognitive deficits in a mouse model of Alzheimer's disease without reducing amyloid and tau pathology

Neurobiology of Disease

Volumn 81, Issue , 2015, Pages 214-224

  Isopi, Elisa ^a   Granzotto, Alberto ^a   Corona, Carlo ^a   Bomba, Manuela ^a   Ciavardelli, Domenico ^a,b   Curcio, Michele ^c   Canzoniero, Lorella M T ^c   Navarra, Riccardo ^a   Lattanzio, Rossano ^a   Piantelli, Mauro ^a   Sensi, Stefano L ^a,d  

^a UNIVERSITY OF CHIETI   (Italy)

^b KORE UNIVERSITY OF ENNA   (Italy)

^c UNIVERSITY OF SANNIO   (Italy)

^d UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

3xTg AD mice; Alzheimer's disease; Amyloid; Brain metabolism; Oxidative stress; Pyruvate; Tau; Zinc

Indexed keywords

AMYLOID BETA PROTEIN; CALCIUM; GLUTAMATE RECEPTOR; LACTATE DEHYDROGENASE; LACTIC ACID; NICOTINAMIDE ADENINE DINUCLEOTIDE; PYRUVATE SODIUM; REACTIVE OXYGEN METABOLITE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE; TAU PROTEIN; ZINC; HISTOCOMPATIBILITY ANTIGEN; NEUROPROTECTIVE AGENT; PYRUVIC ACID;

AEROBIC METABOLISM; AGE; ALZHEIMER DISEASE; AMYLOIDOSIS; ANAEROBIC METABOLISM; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CHRONIC DRUG ADMINISTRATION; COGNITIVE DEFECT; CONTROLLED STUDY; DISEASE EXACERBATION; DRUG SCREENING; EMBRYO; FEMALE; HIPPOCAMPUS; HOMEOSTASIS; LIPID PEROXIDATION; LONG TERM CARE; LONG TERM MEMORY; MALE; MEMORY DISORDER; MOUSE; NERVE CELL EXCITABILITY; NEUROPROTECTION; NONHUMAN; OXIDATIVE STRESS; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; SHORT TERM MEMORY; TAUOPATHY; AGING; ANIMAL; BRAIN CORTEX; CELL CULTURE; COGNITION DISORDERS; COMPLICATION; CYTOLOGY; CYTOSOL; DISEASE MODEL; DRUG EFFECTS; GENE EXPRESSION REGULATION; GENETICS; MAMMALIAN EMBRYO; MAZE TEST; METABOLISM; MITOCHONDRION; NERVE CELL; PHYSIOLOGY; TRANSGENIC MOUSE; ULTRASTRUCTURE;

AGING; ALZHEIMER DISEASE; AMYLOID BETA-PEPTIDES; ANIMALS; CALCIUM; CELLS, CULTURED; CEREBRAL CORTEX; COGNITION DISORDERS; CYTOSOL; DISEASE MODELS, ANIMAL; EMBRYO, MAMMALIAN; GENE EXPRESSION REGULATION; HISTOCOMPATIBILITY ANTIGENS; MAZE LEARNING; MICE; MICE, TRANSGENIC; MITOCHONDRIA; NEURONS; NEUROPROTECTIVE AGENTS; PYRUVIC ACID; TAU PROTEINS;

EID: 84957566741     PISSN: 09699961     EISSN: 1095953X     Source Type: Journal    
DOI: 10.1016/j.nbd.2014.11.013     Document Type: Article

References (83)

1. Alvarez, G., Ramos, M., Ruiz, F., Satrústegui, J., Bogónez, E., 2003. Pyruvate protection against beta-amyloid-induced neuronal death: role of mitochondrial redox state. J. Neurosci. Res. 73, 260-269.
2. Aras, M.A., Aizenman, E., 2011. Redox regulation of intracellular zinc: molecular signaling in the life and death of neurons. Antioxid. Redox Signal. 15, 2249-2263.
3. Bakker, A., Krauss, G.L., Albert, M.S., Speck, C.L., Jones, L.R., Stark, C.E., Yassa, M.A., Bassett, S.S., Shelton, A.L., Gallagher, M., 2012. Reduction of hippocampal hyperactivity improves cognition in amnestic mild cognitive impairment. Neuron 74, 467-474.
4. Billings, L.M., Oddo, S., Green, K.N., McGaugh, J.L., LaFerla, F.M., 2005. Intraneuronal Abeta causes the onset of early Alzheimer's disease-related cognitive deficits in transgenic mice. Neuron 45, 675-688.
5. Blanc, E.M., Keller, J.N., Fernandez, S., Mattson, M.P., 1998. 4-hydroxynonenal, a lipid peroxidation product, impairs glutamate transport in cortical astrocytes. Glia 22, 149-160.
6. Blurton-Jones, M., Kitazawa, M., Martinez-Coria, H., Castello, N.A., Müller, F.-J., Loring, J.F., Yamasaki, T.R., Poon, W.W., Green, K.N., LaFerla, F.M., 2009. Neural stem cells improve cognition via BDNF in a transgenic model of Alzheimer disease. Proc. Natl. Acad. Sci. U. S. A. 106, 13594-13599.
7. Bomba, M., Ciavardelli, D., Silvestri, E., Canzoniero, L.M.T., Lattanzio, R., Chiappini, P., Piantelli, M., Di Ilio, C., Consoli, A., Sensi, S.L., 2013. Exenatide promotes cognitive enhancement and positive brain metabolic changes in PS1-KI mice but has no effects in 3xTg-AD animals. Cell Death Dis. 4, e612.
8. Bouzier-Sore, A.-K., Voisin, P., Canioni, P., Magistretti, P.J., Pellerin, L., 2003. Lactate is a preferential oxidative energy substrate over glucose for neurons in culture. J. Cereb. Blood Flow Metab. 23, 1298-1306.
9. Bush, A.I., 2013. The metal theory of Alzheimer's disease. J. Alzheimers Dis. 33 (Suppl. 1), S277-S281.
10. Canzoniero, L.M.T., Granzotto, A., Turetsky, D.M., Choi, D.W., Dugan, L.L., Sensi, S.L., 2013. nNOS(+) striatal neurons, a subpopulation spared in Huntington's Disease, possess functional NMDA receptors but fail to generate mitochondrial ROS in response to an excitotoxic challenge. Front. Physiol. 4, 112.
11. Chakroborty, S., Kim, J., Schneider, C., Jacobson, C., Molgó, J., Stutzmann, G.E., 2012. Early presynaptic and postsynaptic calcium signaling abnormalities mask underlying synaptic depression in presymptomatic Alzheimer's disease mice. J. Neurosci. Off. J. Soc. Neurosci. 32, 8341-8353.
12. Chen, C.-J., Liao, S.-L., 2003. Zinc toxicity on neonatal cortical neurons: involvement of glutathione chelation. J. Neurochem. 85, 443-453.
13. Choi, D.W., 1988. Glutamate neurotoxicity and diseases of the nervous system. Neuron 1, 623-634.
14. Choi, B.Y., Kim, J.H., Kim, H.J., Yoo, J.H., Song, H.K., Sohn, M., Won, S.J., Suh, S.W., 2013. Pyruvate administration reduces recurrent/moderate hypoglycemia-induced cortical neuron death in diabetic rats. PLoS ONE 8, e81523.
15. Corona, C., Masciopinto, F., Silvestri, E., Viscovo, A.D., Lattanzio, R., Sorda, R.L., Ciavardelli, D., Goglia, F., Piantelli, M., Canzoniero, L.M.T., Sensi, S.L., 2010. Dietary zinc supplementation of 3xTg-AD mice increases BDNF levels and prevents cognitive deficits as well as mitochondrial dysfunction. Cell Death Dis. 1, e91.
16. Corona, C., Frazzini, V., Silvestri, E., Lattanzio, R., La Sorda, R., Piantelli, M., Canzoniero, L.M.T., Ciavardelli, D., Rizzarelli, E., Sensi, S.L., 2011a. Effects of dietary supplementation of carnosine on mitochondrial dysfunction, amyloid pathology, and cognitive deficits in 3xTg-AD mice. PLoS ONE 6, e17971.
17. Corona, C., Pensalfini, A., Frazzini, V., Sensi, S.L., 2011b. New therapeutic targets in Alzheimer's disease: brain deregulation of calcium and zinc. Cell Death Dis. 2, e176.
18. Craddock, T.J.A., Tuszynski, J.A., Chopra, D., Casey, N., Goldstein, L.E., Hameroff, S.R., Tanzi, R.E., 2012. The zinc dyshomeostasis hypothesis of Alzheimer's disease. PLoS ONE 7, e33552.
19. Crouch, P.J., Cimdins, K., Duce, J.A., Bush, A.I., Trounce, I.A., 2007. Mitochondria in aging and Alzheimer's disease. Rejuvenation Res. 10, 349-357.
20. Davis, K.E., Fox, S., Gigg, J., 2014. Increased hippocampal excitability in the 3xTgADmouse model for Alzheimer's disease in vivo. PLoS ONE 9, e91203.
21. Demuro, A., Parker, I., Stutzmann, G.E., 2010. Calcium signaling and amyloid toxicity in Alzheimer disease. J. Biol. Chem. 285, 12463-12468.
22. Desagher, S., Glowinski, J., Prémont, J., 1997. Pyruvate protects neurons against hydrogen peroxide-induced toxicity. J. Neurosci. Off. J. Soc. Neurosci. 17, 9060-9067.
23. Dugan, L.L., Sensi, S.L., Canzoniero, L.M., Handran, S.D., Rothman, S.M., Lin, T.S., Goldberg, M.P., Choi, D.W., 1995. Mitochondrial production of reactive oxygen species in cortical neurons following exposure to N-methyl-D-aspartate. J. Neurosci. Off. J. Soc. Neurosci. 15, 6377-6388.
24. Friedman, D., Honig, L.S., Scarmeas, N., 2012. Seizures and epilepsy in Alzheimer's disease. CNS Neurosci. Ther. 18, 285-294.
25. Fukushima, M., Lee, S.M., Moro, N., Hovda, D.A., Sutton, R.L., 2009. Metabolic and histologic effects of sodium pyruvate treatment in the rat after cortical contusion injury. J. Neurotrauma 26, 1095-1110.
26. Fuso, A., Nicolia, V., Ricceri, L., Cavallaro, R.A., Isopi, E., Mangia, F., Fiorenza, M.T., Scarpa, S., 2012. S-adenosylmethionine reduces the progress of the Alzheimer-like features induced by B-vitamin deficiency in mice. Neurobiol. Aging 33, 1482.e1-1482.e16.
27. Gatta, V., D'Aurora, M., Granzotto, a, Stuppia, L., Sensi, S.L., 2014. Early and sustained altered expression of aging-related genes in young 3xTg-AD mice. Cell Death Dis. 5, e1054.
28. Gomes, A.P., Price, N.L., Ling, A.J.Y., Moslehi, J.J., Montgomery, M.K., Rajman, L., White, J.P., Teodoro, J.S., Wrann, C.D., Hubbard, B.P., Mercken, E.M., Palmeira, C.M., de Cabo, R., Rolo, A.P., Turner, N., Bell, E.L., Sinclair, D.A., 2013. Declining NAD(+) induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging. Cell 155, 1624-1638.
29. Gong, C.-X., Iqbal, K., 2008. Hyperphosphorylation of microtubule-associated protein tau: a promising therapeutic target for Alzheimer disease. Curr. Med. Chem. 15, 2321-2328.
30. Gramsbergen, J.B., Sandberg, M., Kornblit, B., Zimmer, J., 2000. Pyruvate protects against 3-nitropropionic acid neurotoxicity in corticostriatal slice cultures. Neuroreport 11, 2743-2747.
31. Hardy, J.A., Higgins, G.A., 1992. Alzheimer's disease: the amyloid cascade hypothesis. Science 256, 184-185.
32. Hardy, J., Selkoe, D.J., 2002. The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science 297, 353-356.
33. Huang, Y., Mucke, L., 2012. Alzheimer mechanisms and therapeutic strategies. Cell 148, 1204-1222.
34. Itoh, Y., Esaki, T., Shimoji, K., Cook, M., Law, M.J., Kaufman, E., Sokoloff, L., 2003. Dichloroacetate effects on glucose and lactate oxidation by neurons and astroglia in vitro and on glucose utilization by brain in vivo. Proc. Natl. Acad. Sci. U. S. A. 100, 4879-4884.
35. Ittner, L.M., Götz, J., 2011. Amyloid-β and tau-a toxic pas de deux in Alzheimer's disease. Nat. Rev. Neurosci. 12, 65-72.
36. Izumi, Y., Zorumski, C.F., 2010. Neuroprotective effects of pyruvate following NMDAmediated excitotoxic insults in hippocampal slices. Neurosci. Lett. 478, 131-135.
37. Jones, K.A., Baughman, R.W., 1991. Both NMDA and non-NMDA subtypes of glutamate receptors are concentrated at synapses on cerebral cortical neurons in culture. Neuron 7, 593-603.
38. Kim, T.Y., Yi, J.S., Chung, S.J., Kim, D.K., Byun, H.R., Lee, J.Y., Koh, J.Y., 2007. Pyruvate protects against kainate-induced epileptic brain damage in rats. Exp. Neurol. 208, 159-167.
39. Knowles, J.K., Simmons, D.A., Nguyen, T.-V.V., Vander Griend, L., Xie, Y., Zhang, H., Yang, T., Pollak, J., Chang, T., Arancio, O., Buckwalter, M.S., Wyss-Coray, T., Massa, S.M., Longo, F.M., 2013. Small molecule p75NTR ligand prevents cognitive deficits and neurite degeneration in an Alzheimer's mouse model. Neurobiol. Aging 34, 2052-2063.
40. Krieg, A.F., Rosenblum, L.J., Henry, J.B., 1967. Lactate dehydrogenase isoenzymes a comparison of pyruvate-to-lactate and lactate-to-pyruvate assays. Clin. Chem. 13, 196-203.
41. Kudin, A.P., Zsurka, G., Elger, C.E., Kunz, W.S., 2009.Mitochondrial involvement in temporal lobe epilepsy. Exp. Neurol. 218, 326-332.
42. LaFerla, F.M., 2010. Pathways linking Abeta and tau pathologies. Biochem. Soc. Trans. 38, 993-995.
43. Lauderback, C.M., Hackett, J.M., Huang, F.F., Keller, J.N., Szweda, L.I., Markesbery, W.R., Butterfield, D.A., 2001. The glial glutamate transporter, GLT-1, is oxidatively modified by 4-hydroxy-2-nonenal in the Alzheimer's disease brain: the role of Abeta1-42. J. Neurochem. 78, 413-416.
44. Lee, J.Y., Kim, Y.H., Koh, J.Y., 2001. Protection by pyruvate against transient forebrain ischemia in rats. J. Neurosci. Off. J. Soc. Neurosci. 21 (RC171).
45. Li, J.H., Wang, Y.H., Wolfe, B.B., Krueger, K.E., Corsi, L., Stocca, G., Vicini, S., 1998. Developmental changes in localization of NMDA receptor subunits in primary cultures of cortical neurons. Eur. J. Neurosci. 10, 1704-1715.
46. Lin, M.T., Beal, M.F., 2006. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 443, 787-795.
47. Martell, A.M., Smith, R.M., 1995. Critically selected stability constants of metal complexes. National Institute of Standards and Technology, NIST, Gaithersburg, MD.
48. Masciopinto, F., Di Pietro, N., Corona, C., Bomba, M., Pipino, C., Curcio, M., Di Castelnuovo, A., Ciavardelli, D., Silvestri, E., Canzoniero, L.M.T., Sekler, I., Pandolfi, A., Sensi, S.L., 2012. Effects of long-term treatment with pioglitazone on cognition and glucose metabolism of PS1-KI, 3xTg-AD, and wild-type mice. Cell Death Dis. 3, e448.
49. Maus, M., Marin, P., Israël, M., Glowinski, J., Prémont, J., 1999. Pyruvate and lactate protect striatal neurons against N-methyl-D-aspartate-induced neurotoxicity. Eur. J. Neurosci. 11, 3215-3224.
50. Meany, J.E., 2007. Lactate dehydrogenase catalysis: roles of keto, hydrated, and enol pyruvate. J. Chem. Educ. 84, 1520-1523.
51. Michel, C.H., Kumar, S., Pinotsi, D., Tunnacliffe, A., St George-Hyslop, P., Mandelkow, E., Mandelkow, E.-M., Kaminski, C.F., Kaminski Schierle, G.S., 2014. Extracellular monomeric tau protein is sufficient to initiate the spread of tau protein pathology. J. Biol. Chem. 289, 956-967.
52. Miller, L.P., Oldendorf, W.H., 1986. Regional kinetic constants for blood-brain barrier pyruvic acid transport in conscious rats by the monocarboxylic acid carrier. J. Neurochem. 46, 1412-1416.
53. Mongan, P.D., Capacchione, J., West, S., Karaian, J., Dubois, D., Keneally, R., Sharma, P., 2002. Pyruvate improves redox status and decreases indicators of hepatic apoptosis during hemorrhagic shock in swine. Am. J. Physiol. Heart Circ. Physiol. 283, H1634-H1644.
54. Mongan, P.D., Karaian, J., Van Der Schuur, B.M., Via, D.K., Sharma, P., 2003. Pyruvate prevents poly-ADP ribose polymerase (PARP) activation, oxidative damage, and pyruvate dehydrogenase deactivation during hemorrhagic shock in swine. J. Surg. Res. 112, 180-188.
55. Moro, N., Ghavim, S.S., Hovda, D.A., Sutton, R.L., 2011. Delayed sodiumpyruvate treatment improves working memory following experimental traumatic brain injury. Neurosci. Lett. 491, 158-162.
56. Noebels, J., 2011. A perfect storm: converging paths of epilepsy and Alzheimer's dementia intersect in the hippocampal formation. Epilepsia 52 (Suppl. 1), 39-46.
57. Oddo, S., Caccamo, A., Shepherd, J.D., Murphy, M.P., Golde, T.E., Kayed, R., Metherate, R., Mattson, M.P., Akbari, Y., LaFerla, F.M., 2003. Triple-transgenic model of Alzheimer's disease with plaques and tangles: intracellular Abeta and synaptic dysfunction. Neuron 39, 409-421.
58. Palop, J.J., Mucke, L., 2009. Epilepsy and cognitive impairments in Alzheimer disease. Arch. Neurol. 66, 435-440.
59. Pan, J.W., Cavus, I., Kim, J., Hetherington, H.P., Spencer, D.D., 2008. Hippocampal extracellular GABA correlates with metabolism in human epilepsy. Metab. Brain Dis. 23, 457-468.
60. Pellerin, L., Magistretti, P.J., 2012. Sweet sixteen for ANLS. J. Cereb. Blood Flow Metab. 32, 1152-1166.
61. Resende, R., Moreira, P.I., Proença, T., Deshpande, A., Busciglio, J., Pereira, C., Oliveira, C.R., 2008. Brain oxidative stress in a triple-transgenic mouse model of Alzheimer disease. Free Radic. Biol. Med. 44, 2051-2057.
62. Reynolds, I.J., Hastings, T.G., 1995. Glutamate induces the production of reactive oxygen species in cultured forebrain neurons following NMDA receptor activation. J. Neurosci. Off. J. Soc. Neurosci. 15, 3318-3327.
63. Roberts, B.R., Ryan, T.M., Bush, A.I., Masters, C.L., Duce, J.A., 2012. The role of metallobiology and amyloid-β peptides in Alzheimer's disease. J. Neurochem. 120 (Suppl. 1), 149-166.
64. Schägger, H., Bentlage, H., Ruitenbeek, W., Pfeiffer, K., Rotter, S., Rother, C., Böttcher-Purkl, A., Lodemann, E., 1996. Electrophoretic separation of multiprotein complexes from blood platelets and cell lines: technique for the analysis of diseases with defects in oxidative phosphorylation. Electrophoresis 17, 709-714.
65. Sensi, S.L., Canzoniero, L.M., Yu, S.P., Ying, H.S., Koh, J.Y., Kerchner, G.A., Choi, D.W., 1997. Measurement of intracellular free zinc in living cortical neurons: routes of entry. J. Neurosci. Off. J. Soc. Neurosci. 17, 9554-9564.
66. Sensi, S.L., Yin, H.Z., Carriedo, S.G., Rao, S.S., Weiss, J.H., 1999a. Preferential Zn2+ influx through Ca2+-permeable AMPA/kainate channels triggers prolonged mitochondrial superoxide production. Proc. Natl. Acad. Sci. U. S. A. 96, 2414-2419.
67. 2+ permeable AMPA channels and consequent ROS production. Neuroreport 10, 1723-1727.
68. Sensi, S.L., Ton-That, D., Sullivan, P.G., Jonas, E.A., Gee, K.R., Kaczmarek, L.K., Weiss, J.H., 2003. Modulation of mitochondrial function by endogenous Zn2+ pools. Proc. Natl. Acad. Sci. U. S. A. 100, 6157-6162.
69. Sensi, S.L., Rapposelli, I.G., Frazzini, V., Mascetra, N., 2008. Altered oxidant-mediated intraneuronal zinc mobilization in a triple transgenic mouse model of Alzheimer's disease. Exp. Gerontol. 43, 488-492.
70. Sensi, S.L., Paoletti, P., Bush, A.I., Sekler, I., 2009. Zinc in the physiology and pathology of the CNS. Nat. Rev. Neurosci. 10, 780-791.
71. Sheline, C.T., Behrens, M.M., Choi, D.W., 2000. Zinc-induced cortical neuronal death: contribution of energy failure attributable to loss of NAD(+) and inhibition of glycolysis. J. Neurosci. Off. J. Soc. Neurosci. 20, 3139-3146.
72. Sheline, C.T., Cai, A.-L., Zhu, J., Shi, C., 2010. Serum or target deprivation-induced neuronal death causes oxidative neuronal accumulation of Zn2+ and loss of NAD+. Eur. J. Neurosci. 32, 894-904.
73. Stanika, R.I., Pivovarova, N.B., Brantner, C.A., Watts, C.A., Winters, C.A., Andrews, S.B., 2009. Coupling diverse routes of calciumentry tomitochondrial dysfunction and glutamate excitotoxicity. Proc. Natl. Acad. Sci. U. S. A. 106, 9854-9859.
74. Suh, S.W., Aoyama, K., Matsumori, Y., Liu, J., Swanson, R.A., 2005. Pyruvate administered after severe hypoglycemia reduces neuronal death and cognitive impairment. Diabetes 54, 1452-1458.
75. Sutherland, R.J., McDonald, R.J., 1990. Hippocampus, amygdala, and memory deficits in rats. Behav. Brain Res. 37, 57-79.
76. Suzuki, A., Stern, S.A., Bozdagi, O., Huntley, G.W., Walker, R.H., Magistretti, P.J., Alberini, C.M., 2011. Astrocyte-neuron lactate transport is required for long-term memory formation. Cell 144, 810-823.
77. Swerdlow, R.H., Khan, S.M., 2004. A "mitochondrial cascade hypothesis" for sporadic Alzheimer's disease. Med. Hypotheses 63, 8-20.
78. Vossel, K. a, Beagle, A.J., Rabinovici, G.D., Shu, H., Lee, S.E., Naasan, G., Hegde, M., Cornes, S.B., Henry, M.L., Nelson, A.B., Seeley, W.W., Geschwind, M.D., Gorno-Tempini, M.L., Shih, T., Kirsch, H.E., Garcia, P. a, Miller, B.L., Mucke, L., 2013. Seizures and epileptiform activity in the early stages of Alzheimer disease. JAMA Neurol. 70, 1158-1166.
79. Waldbaum, S., Patel, M., 2010.Mitochondria, oxidative stress, and temporal lobe epilepsy. Epilepsy Res. 88, 23-45.
80. Wang, X., Takata, T., Bai, X., Ou, F., Yokono, K., Sakurai, T., 2012. Pyruvate prevents the inhibition of the long-termpotentiation induced by amyloid-β through protein phosphatase 2A inactivation. J. Alzheimers Dis. 30, 665-673.
81. Wang, J.-Z., Xia, Y.-Y., Grundke-Iqbal, I., Iqbal, K., 2013. Abnormal hyperphosphorylation of tau: sites, regulation, and molecular mechanism of neurofibrillary degeneration. J. Alzheimers Dis. 33 (Suppl. 1), S123-S139.
82. Yoo, M.H., Lee, J.-Y., Lee, S.E., Koh, J.-Y., Yoon, Y.H., 2004. Protection by pyruvate of rat retinal cells against zinc toxicity in vitro, and pressure-induced ischemia in vivo. Invest. Ophthalmol. Vis. Sci. 45, 1523-1530.
83. Zilberter, M., Ivanov, A., Ziyatdinova, S., Mukhtarov, M., Malkov, A., Alpár, A., Tortoriello, G., Botting, C.H., Fülöp, L., Osypov, A.A., Pitkänen, A., Tanila, H., Harkany, T., Zilberter, Y., 2013. Dietary energy substrates reverse early neuronal hyperactivity in a mouse model of Alzheimer's disease. J. Neurochem. 125, 157-171.