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2018, Number S1

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Rev Med Inst Mex Seguro Soc 2018; 56 (S1)

Toxicity of beta-amyloid protein during aging: Influence of synaptosomal energy metabolism

Quiroz-Baez R, Arias C

Language: Spanish
References: 34
Page: 18-25
PDF size: 338.20 Kb.


ABSTRACT

Background: Recent evidence suggests that early neurodegenerative events associated with Alzheimer’s disease (AD) probably begin in the synaptic terminal, where it has been reported a large accumulation of β-amyloid protein (Aβ), one of the main factors described in the development of AD. We analyzed the influence of energy metabolism on the toxic effects of Aβ during aging on synaptosomes from neocortex and hippocampus of rats exposed to inhibitors of glycolytic and mitochondrial metabolism and we evaluated the protective effects of some antioxidant compounds.
Methods: Synaptosomes were obtained by differential centrifugation in sucrose gradients and their redox activity was determined with the MTT assay.
Results: The mitochondrial activity of synaptosomes from young rats was not altered by the presence of Aβ; the ones obtained from old rats showed an increase in susceptibility to Aβ; this activity was greater in the synaptic terminals of the hippocampus.
Conclusions: These results provide experimental support for the hypothesis that certain risk factors, such as energy metabolism dysfunction or the aging process itself, may increase vulnerability to Aβ. Hippocampal region is more susceptible to Aβ and its effect increases with age in relation to the neocortex, which would agree with the damage gradient reported in the AD.


REFERENCES

  1. Ferri CP, Prince M, Brayne C, Brodaty H, Fratiglioni L, Ganguli M, et al. Global prevalence of dementia: a Delphi consensus study. Lancet. 2005;366(9503):2112–7.

  2. Alzheimer’s Association. Alzheimer’s disease facts and figures. Alzheimers Dement. 2009;5(3):234-70.

  3. Hebert LE, Scherr PA, Bienias JL, Bennett DA, Evans DA. Alzheimer disease in the US population: prevalence estimates using the 2000 census. Arch Neurol. 2003;60:1119-22.

  4. Selkoe DJ. Alzheimer’s disease is a synaptic failure. Science. 2002;298:789-91.

  5. Arendt T. Alzheimer’s disease as a disorder of mech anisms underlying structural brain self-organization. Neuroscience. 2001;102:723-65.

  6. Terry RD, Katzman R. Life span synapses will there be a primary senile dementia? Neurobiol Aging. 2000;22(3):347-8.

  7. Pietrini P, Alexander GE, Furey ML, Hampel H, Guazzelli M. The neurometabolic landscape of cognitive decline: in vivo studies with positron emission tomography in Alzheimer’s disease. Int J Psychophysiol. 2000;37(1):87-98.

  8. Small GW, Ercoli LM, Silverman DH, Huang SC, Komo S, Bookheimer SY, et al. Cerebral metabolic and cognitive decline in persons at genetic risk for Alzheimer’s disease. Proc Natl Acad Sci USA. 2000;97(11):6037-42.

  9. De Leon M, Bobinski M, Convit A, Wolf O, Insausti R. Usefulness of MRI measures of entorhinal cortex versus hippocampus in AD. Neurology. 2001;56(6):820-1.

  10. De Santi S, de Leon MJ, Rusinek H, Convit A, Tarshish CY, Roche A, et al. Hippocampal formation glucose metabolism and volume losses in MCI and AD. Neurobiol Aging. 2001:22(4):529-39.

  11. Löscher W. Improved method for isolating synaptosomes from 11 regions of one rat brain: Electron microscopic and biochemical characterization and use in the study of drug effect on nerve terminal gamma-animobutyric acid in vivo. J Neurochem. 1985;45:879-89.

  12. Mossman T. Rapid colorimetric assay for cellular growth and survival application to proliferation and cytotoxicity. J Immunol Methods. 1983;65:55-63.

  13. Arias C, Montiel T, Quiroz-Báez R, Massieu L. Beta- Amyloid neurotoxicity is exacerbated during glycolysis inhibition and mitochondrial impairment in the rat hippocampus in vivo and in isolated nerve terminals: implications for Alzheimer’s disease. Exp Neurol. 2002;176(1):163-74.

  14. Montiel T, Quiroz-Baez R, Massieu L, Arias C. Role of oxidative stress on beta-amyloid neurotoxicity elicited during impairment of energy metabolism in the hippocampus: protection by antioxidants. Exp Neurol. 2006;200(2):496-508.

  15. DeKosky ST, Scheff SW, Styren SD. Structural correlates of cognition in dementia: Quantification and assessment of synapse change. Neurodegeneration. 1996;5:417-21.

  16. Terry RD, Masliah E, Hansen AH. Structural basis of the cognitive alterations. En: Terry DR, Katzman R and Bick KL, editores. Alzheimer Disease. New York, USA: Raven Press: 1994. pp. 179-96.

  17. Alvarez XA, Miguel-Hidalgo JJ, Fernández-Novoa L, Cacabelos R. Intrahippocampal injections of the beta- amyloid1–28 fragment induces behavioral deficits in rats. Methods Exp Clin Pharmacol. 1997;19:471-9.

  18. Morimoto K, Yoshimi K, Tonohiro T, Yamada N., Oda T, Kaneko I. Co-injections of beta-amyloid with ibotenic acid induces synergistic loss of rat hippocampal neurons. Neuroscience. 1998;84:479-87.

  19. Copani A, Koh JY, Cotman CW. Beta-Amyloid increases neuronal susceptibility to injury by glucose deprivation. Neuroreport. 1991;2:763-5.

  20. Smyth MD, Kesslack JP, Cummings BJ, Cotman CW. Analysis of brain injury following intrahippocampal administration of beta-amyloid in streptozotocintreated rats. Neurobiol Aging. 1993;15:153-9.

  21. Yakes FM, Houten BV. Motochondrial DNA damage is more extensive and persists longer than nuclear DNA damage in human cells following oxidative stress. Proc Natl Acad Sci USA. 1997;95:514-9.

  22. Sheehan JP, Swerdlow RH, Miller SW, Robert ED, Parks JK, Parker WD, et al. Calcium homeostasis and reactive oxygen species in cells transformed by mitochondria from individuals with sporadic Alzheimer’s Disease. J Neurosci. 1997;17(12):4612-22.

  23. Arias C, Arrieta I, Tapia R. Beta-Amyloid peptide fragment 25–35 potentiates the calcium-dependent release of excitatory amino acids from depolarized hippocampal slices. J Neurosci Res. 1995;1:561-6.

  24. Kauppinen RA, Nicholls DG. Synaptosomal bioenergetics. The role of glycolysis, pyruvate oxidation and response to hypoglycaemia. Eur J Biochem. 1986;158:159-65.

  25. Rafalowska U, Erecinska M, Wilson DF. The effect of acute hypoxia on synaptosomes from rat brain. J Neurochem. 1980;34:1160-5.

  26. Cardoso SM, Pereira C, Oliveira CR. The protective effect of vitamin E, idebenone and reduced glutathione on free radicals mediated injury in rat brain synaptosomes. Biochem Biophys Res Comm. 1998;246:703-10.

  27. Muller DPR, Loyd JK, Wolff OH. Vitamin E and neurological function. Lancet. 1983;1:225-8.

  28. Uto A, Dux E, Kusumoto M, Hossmann K-A. Delayed neuronal death after brief histotoxic hypoxia in vitro. J Neurochem. 1995;64:2185-91.

  29. Janzen EG, Blackburn BJ. Detection and identification of short-leved free radicals by electron spin resonance trapping techniques (spin trapping): photolysis of organolead –tin and –mercury compounds. J Am Chem Soc. 1996;91:4481-90.

  30. Novelli GP, Angiolini P, Tani P. Phenyl-t-butyl-nitrone is active against traumatic shock in rats. Free Radic Res Commun. 1985;1:321-7.

  31. Floyd RA. Role of oxygen free radicals in carcinogenesis and brain ischemia. FASEB J. 1990;4:2587-97.

  32. Idecola C, Zhang F, Casey R. Delayed reduction of ischemic brain injury and neurological deficit s in mice lacking the inducible nitric oxide synthase gene. J Neurosci. 1997;17:9157-64.

  33. Floyd RA. Protective action of nitrone-based free radical traps against oxidative damage to central nervous system. Adv Pharmacol. 1997;38:361-78.

  34. Masliah E, Terry RD, Alford M, De Teresa R, Hansen LA. Cortical and subcortical patterns of synaptophysin- like immunoreactivity in Alzheimer´s disease. Am J Pathol. 1991;138:235-46.




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