Induction of ketosis may improve mitochondrial function and decrease steady-state amyloid-β precursor protein (APP) levels in the aged dog

Brain Research

Volumn 1226, Issue , 2008, Pages 209-217

  Studzinski, Christa M ^a,b   MacKay, William A ^c   Beckett, Tina L ^b   Henderson, Samuel T ^d   Murphy, M Paul ^b   Sullivan, Patrick G ^b   Burnham, W McIntyre ^a  

^a UNIVERSITY OF TORONTO   (Canada)

^b UNIVERSITY OF KENTUCKY   (United States)

^c UNIVERSITY OF TORONTO   (Canada)

^d Accera Inc   (United States)

Author keywords

Alzheimer's disease; Amyloid precursor protein; Amyloid ; Dog; Energy metabolism; Ketone; Mitochondria

Indexed keywords

AMYLOID PRECURSOR PROTEIN; BETA SECRETASE; DECANOIC ACID; MEDIUM CHAIN TRIACYLGLYCEROL; NEOBEE 895; OCTANOIC ACID; UNCLASSIFIED DRUG;

AGING; ALZHEIMER DISEASE; AMYLOIDOSIS; ANIMAL EXPERIMENT; ARTICLE; BRAIN METABOLISM; BRAIN MITOCHONDRION; CONTROLLED STUDY; DOG; FEMALE; FRONTAL LOBE; GLUCOSE METABOLISM; KETOACIDOSIS; MALE; MITOCHONDRIAL RESPIRATION; NONHUMAN; OXIDATIVE STRESS; PARIETAL LOBE; PRIORITY JOURNAL; STEADY STATE;

3-HYDROXYBUTYRIC ACID; AGING; AMYLOID BETA-PROTEIN; AMYLOID BETA-PROTEIN PRECURSOR; AMYLOID PRECURSOR PROTEIN SECRETASES; ANIMALS; DOGS; FEMALE; FRONTAL LOBE; KETOSIS; LIPID PEROXIDATION; MALE; MITOCHONDRIA; MODELS, BIOLOGICAL; OXIDATIVE STRESS; PARIETAL LOBE; TIME FACTORS; TRIGLYCERIDES;

ANIMALIA; CANIS FAMILIARIS;

EID: 48849092902     PISSN: 00068993     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.brainres.2008.06.005     Document Type: Article

References (66)

1. Atamna H., and Frey W.H. Mechanisms of mitochondrial dysfunction and energy deficiency in Alzheimer's disease. Mitochondrion 7 (2007) 297-310
2. Bach A., Guisard D., Metais P., and Debry G. Metabolic effects following a short and medium chain triglycerides load in dogs. 3. Infusion of trinonanoate. Nutr Metabolism 14 (1972) 203-209
3. Bach A., Guisard D., Metais P., and Debry G. Metabolic effects following a short and medium chain triglycerides load in dogs. I. Infusion of an emulsion of short and medium chain triglycerides. Arch Sci Physiol 26 (1972) 121-129
4. Bigl M., Bruckner M.K., Arendt T., Bigl V., and Eschrich K. Activities of key glycolytic enzymes in the brains of patients with Alzheimer's disease. J Neural Transm 106 (1999) 499-511
5. Brown M.R., Sullivan P.G., Dorenbos K.A., Modafferi E.A., Geddes J.W., and Steward O. Nitrogen disruption of synaptoneurosomes: an alternative method to isolate brain mitochondria. J Neurosci Meth 137 (2004) 299-303
6. Bubber P., Haroutunian V., Fisch G., Blass J.P., and Gibson G.E. Mitochondrial abnormalities in Alzheimer brain: mechanistic implications. Ann Neurol 57 (2005) 695-703
7. Butterworth R.F., and Besnard A.M. Thiamine-dependent enzyme changes in temporal cortex of patients with Alzheimer's disease. Metab Brain Dis 5 (1990) 179-184
8. Caspersen C., Wang N., Yao J., Sosunov A., Chen X., Lustbader J.W., Xu H.W., Stern D., McKhann G., and Yan S.D. Mitochondrial Aβ: a potential focal point for neuronal metabolic dysfunction in Alzheimer's disease. FASEB J 19 (2006) 2040-2041
9. Chagnon P., Betard C., Robitaille Y., Cholette A., and Gauvreau D. Distribution of brain cytochrome oxidase activity in various neurodegenerative diseases. Neuroreport 6 (1995) 711-715
10. Cummings B.J., Head E., Ruehl W., Milgram N.W., and Cotman C.W. The canine as an animal model of human aging and dementia. Neurobiol Aging 17 (1996) 259-268
11. Cummings B.J., Satou T., Head E., Milgram N.W., Cole G.M., Savage M.J., Podlisny M.B., Selkoe D.J., Siman R., Greenberg B.D., and Cotman C.W. Diffuse plaques contain C-terminal A beta 42 and not A beta 40: evidence from cats and dogs. Neurobiol Aging 17 (1996) 653-659
12. Das P., Howard V., Loosbrock N., Dickson D., Murphy M.P., and Golde T.E. Amyloid-beta immunization effectively reduces amyloid deposition in FcRgamma-/- knock-out mice. J Neurosci 23 (2003) 8532-8538
13. Das P., Murphy M.P., Younkin L.H., Younkin S., and Golde T.E. Reduced effectiveness of A[beta]1-42 immunization in APP transgenic mice with significant amyloid deposition. Neurobiol Aging 22 (2001) 721-727
14. Finn P.F., and Dice J.F. Ketone bodies stimulate chaperone-mediated autophagy. J Biol Chem 280 (2005) 25864-25870
15. Gabuzda D., Busciglio J., Chen L.B., Matsudaira P., and Yankner B.A. Inhibition of energy metabolism alters the processing of amyloid precursor protein and induces potentially amyloidogenic derivative. J Biol Chem 269 (1994) 13623-13628
16. Gasparini L., Benuissi L., Bianchetti A., Binetti G., Curti D., Govoni S., Moraschi S., Racchi M., and Trabucchi M. Energy metabolism inhibition impairs amyloid precursor protein secretion from Alzheimer's fibroblasts. Neurosci Lett 263 (1999) 197-200
17. Gasparini L., Racchi M., Benussi L., Curti D., Binetti G., Bianchetti A., Trabucchi M., and Govoni S. Effect of energy shortage and oxidative stress on amyloid precursor protein metabolism in COS cells. Neurosci Lett 231 (1997) 113-117
18. Gibson G.E., Sheu K.F., and Blass J.P. Abnormalities of mitochondrial enzymes in Alzheimer disease. J Neural Transm 105 (1998) 855-870
19. Gibson G.E., Zhang H., Sheu K.F., Bogdanovich N., Lindsay J.G., Lannfelt L., Vestling M., and Cowburn R.F. Alpha-ketoglutarate dehydrogenase in Alzheimer brains bearing the APP670/671 mutation. Ann Neurol 44 (1998) 676-681
20. Guisard D., Bach A., Debry G., and Metais P. Metabolic effects following a short and medium chain triglycerides load in dogs. II. Influence of the infused fat quantity. Arch Sci Physiol 26 (1972) 195-205
21. Guzman M., and Blazquez C. Ketone body synthesis in the brain: possible neuroprotective effects. Prostag Leukotr Ess 70 (2004) 287-292
22. Haxby J.V., and Rapoport S.I. Abnormalities of regional brain metabolism in Alzheimer's disease and their relation to functional impairment. Prog Neuro-Psychoph 10 (1986) 427-438
23. Head E., Barrett E.G., Murphy M.P., Das P., Nistor M., Sarsoza F., Glabe C.C., Kayed R., Milton S., Vasilevko V., Milgram N.W., Agadjanyan M.G., Cribbs D.H., and Cotman C.W. Immunization with fibrillar A[beta]1-42 in young and aged canines: antibody generation and characteristics, and effects on CSF and brain A[beta]. Vaccine 24 (2006) 2824-2834
24. Head E., Liu J., Hagen T.M., Muggenburg B.A., Milgram N.W., Ames B.N., and Cotman C.W. Oxidative damage increases with age in a canine model of human brain aging. J Neurochem 82 (2002) 375-381
25. Head E., McCleary R., Hahn F.F., Milgram N.W., and Cotman C.W. Region-specific age at onset of beta-amyloid in dogs. Neurobiol Aging 21 (2000) 89-96
26. Head E., Milgram N.W., and Cotman C.W. Neurobiological models of aging in the dog and other vertebrate species. In: Hof P.R., and Mobbs C.V. (Eds). Functional Neurobiology of Aging (2001), Academic Press, San Diego 457-468
27. Head E., and Torp R. Insights into Abeta and presenilin from a canine model of human brain aging. Neurobiol Dis 9 (2002) 1-10
28. Hoyer S. Oxidative metabolism deficiencies in brains of patients with Alzheimer's disease. Acta Neurol Scand Supp 165 (1996) S18-S24
29. Isselbacher K.J. Mechanisms of absorption of long and medium chain triglycerides. In: Senior J.R. (Ed). Medium Chain Triglycerides (1968), University of Pennsylvania Press, Philadelphia 21-34
30. Kashiwaya Y., Takeshima T., Mori N., Nakashima K., Clarke K., and Veech R.L. d-beta-hydroxybutyrate protects neurons in models of Alzheimer's and Parkinson's disease. P Natl Acad Sci USA 97 (2000) 5440-5444
31. Kawarabayashi T., Younkin L.H., Saido T.C., Shoji M., Ashe K.H., and Younkin S.G. Age-dependent changes in brain, CSF, and plasma amyloid-β protein in the Tg2576 transgenic mouse model of Alzheimer's disease. J Neurosci 21 (2001) 372-381
32. Kish S.J. Brain energy metabolizing enzymes in Alzheimer's disease: alpha-ketoglutarate dehydrogenase complex and cytochrome oxidase. Ann NY Acad Sci 826 (1997) 218-228
33. Kish S.J., Bergeron C., Rajput A., Dozic S., Mastrogiacomo F., Chang L.J., Wilson J.M., DiStefano L.M., and Nobrega J.N. Brain cytochrome oxidase in Alzheimer's disease. J Neurochem 59 (1992) 776-779
34. Ko L.W., Sheu K.F., Thaler H.T., Markesbery W.R., and Blass J.P. Selective loss of KGDHC-enriched neurons in Alzheimer temporal cortex: does mitochondrial variation contribute to selective vulnerability?. J Mol Neurosci 17 (2001) 361-369
35. Kreiner J. Reconstruction of neocortical lesions within the dog's brain: instructions. Acta Biol Exp 26 (1966) 221-244
36. Liguri G., Taddei N., Nassi P., Latorraca S., Nediani C., and Sorbi S. Changes in Na+,K(+)-ATPase and some soluble enzymes related to energy metabolism in brains of patients with Alzheimer's disease. Neurosci Lett 112 (1990) 338-342
37. London E.D., Ohata M., Takei H., French A.W., and Rapoport S.I. Regional cerebral metabolic rate for glucose in beagle dogs of different ages. Neurobiol Aging 4 (1983) 121-126
38. Manczak M., Anekonda T.S., Henson E., Park B.S., Quinn J., and Reddy P.H. Mitochondria are a direct site of Aβ accumulation in Alzheimer's disease neurons: implications for free radical generation and oxidative damage in disease progression. Hum Mol Gen 15 (2006) 1437-1449
39. Mastrogiacoma F., Lindsay J.G., Bettendorff L., Rice J., and Kish S.J. Brain protein and alpha-ketoglutarate dehydrogenase complex activity in Alzheimer's disease. Ann Neurol 39 (1996) 592-598
40. Minoshima S., Giordani B., Berent S., Frey K.A., Foster N.L., and Kuhl D.E. Metabolic reduction in the posterior cingulate cortex in very early Alzheimer's disease. Ann Neurol 42 (1997) 85-95
41. Mutisya E.M., Bowling A.C., and Beal M.F. Cortical cytochrome oxidase activity is reduced in Alzheimer's disease. J Neurochem 63 (1994) 2179-2184
42. Parker Jr. W.D., Filley C.M., and Parks J.K. Cytochrome oxidase deficiency in Alzheimer's disease. Neurology 40 (1990) 1302-1303
43. Parker Jr. W.D., Parks J., Filley C.M., and Kleinschmidt-DeMasters B.K. Electron transport chain defects in Alzheimer's disease brain. Neurology 44 (1994) 1090-1096
44. Perry E.K., Perry R.H., Tomlinson B.E., Blessed G., and Gibson P.H. Coenzyme a-acetylating enzymes in Alzheimer's disease: possible cholinergic 'compartment' of pyruvate dehydrogenase. Neurosci Lett 18 (1980) 105-110
45. Reddy P.H., McWeeney S., Park B.S., Manczak M., Gutala R.V., Partovi D., Jung Y., Yau V., Searles R., Mori M., and Quinn J. Gene expression profiles of transcripts in amyloid precursor protein transgenic mice: up-regulation of mitochondrial metabolism and apoptotic genes is an early cellular change in Alzheimer's disease. Hum Mol Gen 13 (2004) 1225-1240
46. Reger M.A., Henderson S.T., Hale C., Cholerton B., Baker L.D., Watson G.S., Hyde K., Chapman D., and Craft S. Effects of beta-hydroxybutyrate on cognition in memory-impaired adults. Neurobiol Aging 25 (2004) 311-314
47. Reiman E.M., Chen K., Alexander G.E., Caselli R.J., Bandy D., Osborne D., Saunders A.M., and Hardy J. Functional brain abnormalities in young adults at genetic risk for late-onset Alzheimer's dementia. Proc Natl Acad Sci USA 101 (2004) 284-289
48. Rochette M.J., and Murphy M.P. Gamma-secretase: substrates and inhibitors. Mol Neurobiol 26 (2002) 81-95
49. Sato K., Kashiwaya Y., Keon C.A., Tsuchiya N., King M.T., Radda G.K., Chance B., Clarke K., and Veech R.L. Insulin, ketone bodies and mitochondrial energy transduction. FASEB J 9 (1995) 651-658
50. Selkoe D.J. Alzheimer's disease: genes, proteins, and therapy. Physiol Rev 81 (2001) 741-766
51. Sheu K.F., Cooper A.J., Koike K., Koike M., Lindsay J.G., and Blass J.P. Abnormality of the alpha-ketoglutarate dehydrogenase complex in fibroblasts from familial Alzheimer's disease. Ann Neurol 35 (1994) 312-318
52. Sheu K.F., Kim Y.T., Blass J.P., and Weksler M.E. An immunochemical study of the pyruvate dehydrogenase deficit in Alzheimer's disease brain. Ann Neurol 17 (1985) 444-449
53. Sims N.R. Energy metabolism, oxidative stress and neuronal degeneration in Alzheimer's disease. Neurodegeneration 5 (1996) 435-440
54. Singh I.N., Sullivan P.G., Deng Y., Mbye L.H., and Hall E.D. Time course of post-traumatic mitochondrial oxidative damage and dysfunction in a mouse model of focal traumatic brain injury: implications for neuroprotective therapy. J Cerebr Blood F Met 26 (2006) 1407-1418
55. Sorbi S., Bird E.D., and Blass J.P. Decreased pyruvate dehydrogenase complex activity in Huntington and Alzheimer brain. Ann Neurol 13 (1983) 72-78
56. Stokin G.B., Lillo C., Falzone T.L., Brusch R.G., Rockenstein E., Mount S.L., Raman R., Davies P., Masliah E., Williams D.S., and Goldstein L.S.B. Axonopathy and transport deficits early in the pathogenesis of Alzheimer's disease. Science 307 (2005) 1282-1288
57. Sullivan P.G., and Brown M.R. Mitochondrial aging and dysfunction in Alzheimer's disease. Prog Neuro-Psychoph 29 (2005) 407-410
58. Sullivan P.G., Dube C., Dorenbos K., Steward O., and Baram T.Z. Mitochondrial uncoupling protein-2 protects the immature brain from excitotoxic neuronal death. Ann Neurol 53 (2003) 711-717
59. Sullivan P.G., Geiger J.D., Mattson M.P., and Scheff S.W. Dietary supplement creatine protects against traumatic brain injury. Ann Neurol 48 (2000) 723-729
60. Sullivan P.G., Rippy N.A., Dorenbos K., Concepcion R.C., Agarwal A.K., and Rho J.M. The ketogenic diet increases mitochondrial uncoupling protein levels and activity. Ann Neurol 55 (2004) 576-580
61. Van der Auwera I., Wera S., Van Leuven F., and Henderson S.T. A ketogenic diet reduces amyloid beta 40 and 42 in a mouse model of Alzheimer's disease. Nutr Metabolism 2 (2005) 28-35
62. Van Itallie T.B., and Nufert B.A. Ketones: metabolism's ugly duckling. Nutr Rev 61 (2003) 327-341
63. Vander Borght T., Minoshima S., Giordani B., Foster N.L., Frey K.A., Berent S., Albin R.L., Koeppe R.A., and Kuhl D.E. Cerebral metabolic differences in Parkinson's and Alzheimer's diseases matched for dementia severity. J Nucl Med 38 (1997) 797-802
64. Velliquette R.A., O'Connor T., and Vassar R. Energy inhibition elevates β-secretase levels and activity and is potentially amyloidogenic in APP transgenic mice: possible early events in Alzheimer's disease pathogenesis. J Neurosci 25 (2005) 10874-10883
65. Webster M.-T., Pearce B.R., Bowen D.M., and Francis P.T. The effects of perturbed energy metabolism on the processing of amyloid precursor protein in PC12 cells. J Neur Transm 105 (1998) 839-853
66. Yates C.M., Butterworth J., Tennant M.C., and Gordon A. Enzyme activities in relation to pH and lactate in postmortem brain in Alzheimer-type and other dementias. J Neurochem 55 (1990) 1624-1630