Reduction of cerebral cortical [3H]ouabain binding site (Na+,K+ATPase) density in dementia as evaluated in fresh human cerebral cortical biopsies

Thomas A. Schmidt, Steen Hasselbalch, Jim S. Larsen, Henning Bundgaard, Marianne Juhler, Keld Kjeldsen

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    Na+,K+,ATPase density in human cerebral cortex was for the first time studied by vanadate facilitated [3H]ouabain binding to intact samples. Fresh human cerebral cortical biopsies were obtained as a result of diagnostic frontal lobe biopsy from patients with normal pressure hydrocephalus (NPH) syndrome and associated dementia. For control measurements post-mortem samples were obtained from patients without clinically observed dementia. [3H]ouabain binding kinetics were evaluated: when incubating samples in 1 μM [3H]ouabain binding equilibrium was obtained after 6 h of incubation, non-specific uptake and retention amounted to only 2.3% of total uptake and retention of [3H]ouabain and release of specifically bound [3H]ouabain during washout in the cold occurred only slowly (T( 1/4 ) = 37 h). Evaluation of receptor affinity for ouabain was in agreement with a heterogeneous population of [3H]ouabain binding sites. [3H]Ouabain binding was significantly reduced after frozen storage of samples before measurements. Post-mortem degradation of cerebral [3H]ouabain binding sites occurred only slowly (T( 1/4 ) = 75 h). No significant variation in [3H]ouabain binding site density was observed between the cerebral lobes with occipital, parietal and temporal values (means ± S.E.M., n = 5) amounting to 10 281 ± 649, 11 267 ± 1011 and 9263 ± 615 pmol/g wet wt., respectively. [3H]ouabain binding measured in frontal cortical samples gave values of (means ± S.E.M., n = 5) 4274 ± 1020 and 11 397 ± 976 pmol/g wet wt. (Δ% = 62; P < 0.05) in patients with dementia and controls, respectively. Human cerebral cortical capacity for active K+ uptake was around 37- and 16-fold greater than in skeletal muscular and myocardial tissue, respectively.

    Sider (fra-til)281-287
    Antal sider7
    TidsskriftCognitive Brain Research
    Udgave nummer4
    StatusUdgivet - 1 nov. 1996

    Fingeraftryk Udforsk hvilke forskningsemner 'Reduction of cerebral cortical [<sup>3</sup>H]ouabain binding site (Na<sup>+</sup>,K<sup>+</sup>ATPase) density in dementia as evaluated in fresh human cerebral cortical biopsies' indeholder.