Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Ouabain Binding in the Human Brain: Effects of Alzheimer's Disease and Aging

Ouabain Binding in the Human Brain: Effects of Alzheimer's Disease and Aging Abstract • We studied Na+,K+-adenosine triphosphatase by assaying specific tritiated ouabain binding in the frontal cortex, temporal cortex, hippocampus, putamen, cerebellum, and cerebral microvessels in subjects with Alzheimer's disease and control subjects. Ouabain binds specifically, in a saturable manner, and with a high affinity to a single class of binding sites in all the tissues studied. The density of ouabain binding sites was highest in cerebellum and frontal cortex (∼ 40 pmol/mg of protein); intermediate in temporal cortex, hippocampus, and putamen; and lowest in brain microvessels (∼ 8 pmol/mg of protein). The dissociation constant of binding was about 30 nmol/L in all tissues. In control subjects, there were no age-related alterations in ouabain binding, nor was there any correlation between ouabain binding and postmortem delay. However, there was a marked decrease in brain ouabain binding in subjects with Alzheimer's disease when compared with agematched controls, especially in the cerebral cortex. Ouabain binding was also significantly decreased in the cerebellum and putamen of subjects with Alzheimer's disease even though these brain regions are not particularly affected in this disease. Ouabain binding to brain microvessels, which constitute the blood-brain barrier, was not significantly decreased in subjects with Alzheimer's disease. The decreased specific ouabain binding in the brain of subjects with Alzheimer's disease probably reflects the loss of neuronal membranes. References 1. Frackowiak RSJ, Pozzilli C, Legg NJ, et al. Regional cerebral oxygen supply and utilization in dementia: a clinical and physiological study with oxygen-15 and positron tomography . Brain . 1981;104:753-778.Crossref 2. Barclay LL, Zemcov A, Blass JP, McDowell F. Rates of decrease of cerebral blood flow in progressive dementias . Neurology . 1984;34:1555-1560.Crossref 3. Ferris SH, de Leon MJ, Wolf AP, et al. Positron emission tomography in the study of aging and senile dementia . Neurobiol Aging . 1980;1:127-131.Crossref 4. Foster NL, Chase TN, Fedio P, Patronas NJ, Brooks RA, DiChiro G. Alzheimer's disease: focal cortical changes shown by positron emission tomography . Neurology . 1983;33:961-965.Crossref 5. Friedland RP, Budinger TF, Ganz E, et al. Regional cerebral metabolic alterations in dementia of the Alzheimer type: positron emission tomography with 18F-fluorodeoxyglucose . J Comput Assist Tomogr . 1983;7:590-598.Crossref 6. Metter EJ, Riege WH, Kameyama M, Kuhl DE, Phelps ME. Cerebral metabolic relationships for selected brain regions in Alzheimer's, Huntington's, and Parkinson's disease . J Cereb Blood Flow Metab . 1984;4:500-506.Crossref 7. Duara R, Grady C, Haxby J, et al, Positron emission tomography in Alzheimer disease . Neurology . 1986;36:879-887.Crossref 8. Kuhl DE, Metter EJ, Riege WH, Phelps ME. Effects of human aging on patterns of local cerebral glucose utilization determined by (18F)fluorodeoxyglucose method . J Cereb Blood Flow Metab . 1982;2:163-171.Crossref 9. de Leon MJ, George AE, Ferris SH. Computed tomography and positron emission tomography correlates of cognitive decline in aging and senile dementia . In: Toon LW, ed. Handbook for Clinical Memory Assessment of Older Adults . Washington, DC: American Psychological Association; 1986:367-382. 10. Astrup J, Sorensen PM, Sorensen HP. Oxygen and glucose consumption related to Na+-K+ transport in canine brain . Stroke . 1981;12:726-730.Crossref 11. Mata M, Fink DJ, Gainer H, et al. Activity-dependent energy metabolism in rat posterior pituitary reflects sodium-pump activity . J Neurochem . 1980;34:213-215.Crossref 12. Spyropoulos AC, Rainbow TC. Quantitative autoradiography of [3H]ouabain binding sites in rat brain . Brain Res . 1984;322:189-193.Crossref 13. Harik SI, Doull GH, Dick APK. Specific ouabain binding to brain microvessels and choroid plexus . J Cereb Blood Flow Metab . 1985;5:156-160.Crossref 14. Harik SI. Blood-brain barrier sodium-potassium pump: modulation by central noradrenergic innervation . Proc Natl Acad Sci USA . 1986;83:4067-4070.Crossref 15. Khachaturian ZS. Diagnosis of Alzheimer's disease . Arch Neurol . 1985;42:1097-1105.Crossref 16. Kalaria RN, Harik SI. Adenosine receptors and the nucleoside transporter in human brain vasculature . J Cereb Blood Flow Metab . 1988, 8:32-39.Crossref 17. Kalaria RN, Gravina SA, Schmidley JW, Perry G, Harik SI. Glucose transporter of the human brain and blood-brain barrier . Ann Neurol . 1988;24:757-764.Crossref 18. Dick APK, Harik SI, Klip A, Walker DM. Identification and characterization of the glucose transporter of the blood-brain barrier by cytochalasin B binding and immunological reactivity . Proc Natl Acad Sci USA . 1984;81:7233-7237.Crossref 19. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the folin phenol reagent . J Biol Chem . 1951;193:265-275. 20. LaManna JC, Doull G, McCracken K, Harik SI. (Na+,K+)-ATPase activity in ouabain-binding sites in the cerebral cortex of young and aged Fischer-344 rats . Gerontology . 1983;29:242-247.Crossref 21. Scatchard G. The attractions of proteins for small molecules and ions . Ann NY Acad Sci . 1949;51:660-672.Crossref 22. Kalaria RN, Harik SI. Reduced glucose transporter at the blood-brain barrier and in cerebral cortex in Alzheimer Disease. J Neuro Chem. In press. 23. Hauger R, Luu MD, Goodwin FK, Paul SM. Characterization of [3H]ouabain binding sites in human brain, platelet, and erythrocyte . J Neurochem . 1985;44:1704-1708.Crossref 24. Hollander J, Barrows C Jr. Enzymatic studies in senescent rodent brains . J Gerontol . 1968;23:174-179.Crossref 25. Sun A, Samorajski T. The effects of age and alcohol on (Na+,K+)-ATPase activity of whole homogenate and synaptosomes prepared from mouse and human brain . J Neurochem . 1975;24:161-164.Crossref 26. Poole LB, Liu M-S, Landfield PW. Kinetic studies of Na+,K+-ATPase enzyme system in brain and heart of aging rats . Am J Physiol . 1984;247:R850-R855. 27. Kennedy RH, Akera T, Katano Y. Aging: effects on sodium- and potassium-activated adenosine triphosphatase activity and ouabain binding sites in rat brain . J Gerontol . 1985;40:401-408.Crossref 28. Kendrick ZV, Goldfarb AH, Roberts J, Baskin SI. The effects of age on the activity and ouabain inhibition of Na+,K+-ATPase purified from tissues of the Fischer-344 rat . In: Adelman R, Roberts J, Baker GT III, Baskin SI, Cristofalo VJ, eds. Neural Regulatory Mechanisms During Aging . New York, NY: Alan R Liss Inc; 1980:223-225. 29. Calderini G, Bonetti AC, Battistella A, Crews FT, Toffano G. Biochemical changes of rat brain membranes with aging . Neurochem Res . 1983;8:483-492.Crossref 30. DeKoski ST, Bass NH. Aging, senile dementia, and the intralaminar microchemistry of cerebral cortex . Neurology . 1982;32:1227-1233.Crossref 31. Hauger R, Luu MD, Meyer DK, Goodwin FK, Paul SM. Characterization of 'high-affinity' [3H]ouabain binding in the rat central nervous system . J Neurochem . 1985;44:1709-1715.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Neurology American Medical Association

Ouabain Binding in the Human Brain: Effects of Alzheimer's Disease and Aging

Download PDF
4 pages

Loading next page...
 
/lp/american-medical-association/ouabain-binding-in-the-human-brain-effects-of-alzheimer-s-disease-and-WB76RXWhq6

References (37)

Publisher
American Medical Association
Copyright
Copyright © 1989 American Medical Association. All Rights Reserved.
ISSN
0003-9942
eISSN
1538-3687
DOI
10.1001/archneur.1989.00520450021013
Publisher site
See Article on Publisher Site

Abstract

Abstract • We studied Na+,K+-adenosine triphosphatase by assaying specific tritiated ouabain binding in the frontal cortex, temporal cortex, hippocampus, putamen, cerebellum, and cerebral microvessels in subjects with Alzheimer's disease and control subjects. Ouabain binds specifically, in a saturable manner, and with a high affinity to a single class of binding sites in all the tissues studied. The density of ouabain binding sites was highest in cerebellum and frontal cortex (∼ 40 pmol/mg of protein); intermediate in temporal cortex, hippocampus, and putamen; and lowest in brain microvessels (∼ 8 pmol/mg of protein). The dissociation constant of binding was about 30 nmol/L in all tissues. In control subjects, there were no age-related alterations in ouabain binding, nor was there any correlation between ouabain binding and postmortem delay. However, there was a marked decrease in brain ouabain binding in subjects with Alzheimer's disease when compared with agematched controls, especially in the cerebral cortex. Ouabain binding was also significantly decreased in the cerebellum and putamen of subjects with Alzheimer's disease even though these brain regions are not particularly affected in this disease. Ouabain binding to brain microvessels, which constitute the blood-brain barrier, was not significantly decreased in subjects with Alzheimer's disease. The decreased specific ouabain binding in the brain of subjects with Alzheimer's disease probably reflects the loss of neuronal membranes. References 1. Frackowiak RSJ, Pozzilli C, Legg NJ, et al. Regional cerebral oxygen supply and utilization in dementia: a clinical and physiological study with oxygen-15 and positron tomography . Brain . 1981;104:753-778.Crossref 2. Barclay LL, Zemcov A, Blass JP, McDowell F. Rates of decrease of cerebral blood flow in progressive dementias . Neurology . 1984;34:1555-1560.Crossref 3. Ferris SH, de Leon MJ, Wolf AP, et al. Positron emission tomography in the study of aging and senile dementia . Neurobiol Aging . 1980;1:127-131.Crossref 4. Foster NL, Chase TN, Fedio P, Patronas NJ, Brooks RA, DiChiro G. Alzheimer's disease: focal cortical changes shown by positron emission tomography . Neurology . 1983;33:961-965.Crossref 5. Friedland RP, Budinger TF, Ganz E, et al. Regional cerebral metabolic alterations in dementia of the Alzheimer type: positron emission tomography with 18F-fluorodeoxyglucose . J Comput Assist Tomogr . 1983;7:590-598.Crossref 6. Metter EJ, Riege WH, Kameyama M, Kuhl DE, Phelps ME. Cerebral metabolic relationships for selected brain regions in Alzheimer's, Huntington's, and Parkinson's disease . J Cereb Blood Flow Metab . 1984;4:500-506.Crossref 7. Duara R, Grady C, Haxby J, et al, Positron emission tomography in Alzheimer disease . Neurology . 1986;36:879-887.Crossref 8. Kuhl DE, Metter EJ, Riege WH, Phelps ME. Effects of human aging on patterns of local cerebral glucose utilization determined by (18F)fluorodeoxyglucose method . J Cereb Blood Flow Metab . 1982;2:163-171.Crossref 9. de Leon MJ, George AE, Ferris SH. Computed tomography and positron emission tomography correlates of cognitive decline in aging and senile dementia . In: Toon LW, ed. Handbook for Clinical Memory Assessment of Older Adults . Washington, DC: American Psychological Association; 1986:367-382. 10. Astrup J, Sorensen PM, Sorensen HP. Oxygen and glucose consumption related to Na+-K+ transport in canine brain . Stroke . 1981;12:726-730.Crossref 11. Mata M, Fink DJ, Gainer H, et al. Activity-dependent energy metabolism in rat posterior pituitary reflects sodium-pump activity . J Neurochem . 1980;34:213-215.Crossref 12. Spyropoulos AC, Rainbow TC. Quantitative autoradiography of [3H]ouabain binding sites in rat brain . Brain Res . 1984;322:189-193.Crossref 13. Harik SI, Doull GH, Dick APK. Specific ouabain binding to brain microvessels and choroid plexus . J Cereb Blood Flow Metab . 1985;5:156-160.Crossref 14. Harik SI. Blood-brain barrier sodium-potassium pump: modulation by central noradrenergic innervation . Proc Natl Acad Sci USA . 1986;83:4067-4070.Crossref 15. Khachaturian ZS. Diagnosis of Alzheimer's disease . Arch Neurol . 1985;42:1097-1105.Crossref 16. Kalaria RN, Harik SI. Adenosine receptors and the nucleoside transporter in human brain vasculature . J Cereb Blood Flow Metab . 1988, 8:32-39.Crossref 17. Kalaria RN, Gravina SA, Schmidley JW, Perry G, Harik SI. Glucose transporter of the human brain and blood-brain barrier . Ann Neurol . 1988;24:757-764.Crossref 18. Dick APK, Harik SI, Klip A, Walker DM. Identification and characterization of the glucose transporter of the blood-brain barrier by cytochalasin B binding and immunological reactivity . Proc Natl Acad Sci USA . 1984;81:7233-7237.Crossref 19. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the folin phenol reagent . J Biol Chem . 1951;193:265-275. 20. LaManna JC, Doull G, McCracken K, Harik SI. (Na+,K+)-ATPase activity in ouabain-binding sites in the cerebral cortex of young and aged Fischer-344 rats . Gerontology . 1983;29:242-247.Crossref 21. Scatchard G. The attractions of proteins for small molecules and ions . Ann NY Acad Sci . 1949;51:660-672.Crossref 22. Kalaria RN, Harik SI. Reduced glucose transporter at the blood-brain barrier and in cerebral cortex in Alzheimer Disease. J Neuro Chem. In press. 23. Hauger R, Luu MD, Goodwin FK, Paul SM. Characterization of [3H]ouabain binding sites in human brain, platelet, and erythrocyte . J Neurochem . 1985;44:1704-1708.Crossref 24. Hollander J, Barrows C Jr. Enzymatic studies in senescent rodent brains . J Gerontol . 1968;23:174-179.Crossref 25. Sun A, Samorajski T. The effects of age and alcohol on (Na+,K+)-ATPase activity of whole homogenate and synaptosomes prepared from mouse and human brain . J Neurochem . 1975;24:161-164.Crossref 26. Poole LB, Liu M-S, Landfield PW. Kinetic studies of Na+,K+-ATPase enzyme system in brain and heart of aging rats . Am J Physiol . 1984;247:R850-R855. 27. Kennedy RH, Akera T, Katano Y. Aging: effects on sodium- and potassium-activated adenosine triphosphatase activity and ouabain binding sites in rat brain . J Gerontol . 1985;40:401-408.Crossref 28. Kendrick ZV, Goldfarb AH, Roberts J, Baskin SI. The effects of age on the activity and ouabain inhibition of Na+,K+-ATPase purified from tissues of the Fischer-344 rat . In: Adelman R, Roberts J, Baker GT III, Baskin SI, Cristofalo VJ, eds. Neural Regulatory Mechanisms During Aging . New York, NY: Alan R Liss Inc; 1980:223-225. 29. Calderini G, Bonetti AC, Battistella A, Crews FT, Toffano G. Biochemical changes of rat brain membranes with aging . Neurochem Res . 1983;8:483-492.Crossref 30. DeKoski ST, Bass NH. Aging, senile dementia, and the intralaminar microchemistry of cerebral cortex . Neurology . 1982;32:1227-1233.Crossref 31. Hauger R, Luu MD, Meyer DK, Goodwin FK, Paul SM. Characterization of 'high-affinity' [3H]ouabain binding in the rat central nervous system . J Neurochem . 1985;44:1709-1715.Crossref

Journal

Archives of Neurology – American Medical Association

Published: Sep 1, 1989

There are no references for this article.