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P2–022: Streptozotocin–intracerebroventricularly treated rats: Behavioral, neurochemical and structural resembling to the human sporadic type of Alzheimer's disease
Author(s) -
Salkovic-Petrisic Melita,
Tribl Florian,
Osmanovic Jelena,
Schmidt Manuela,
Hoyer Siegfried,
Riederer Peter
Publication year - 2006
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2006.05.859
Subject(s) - neurochemical , morris water navigation task , streptozotocin , medicine , endocrinology , glycogen synthase , insulin degrading enzyme , hippocampus , gsk 3 , protein kinase b , chemistry , insulin , kinase , diabetes mellitus , phosphorylation , biochemistry
critical role in Alzheimer’s disease pathology. Steady-state A levels are regulated by multiple factors that include the rate at which A is generated, degraded, and cleared from the brain. Recently, it has been proposed that brain A efflux into the periphery may act as a “sink” for rapid clearance. Objectives: We directly examined the contribution of the liver in clearing peripheral A in the rat. The rate of A clearance with the liver removed from circulation was compared both to control animals and those without intact kidneys. Methods: Adult male Sprague Dawley rats (200-250g) were randomly assigned to one of three conditions: sham surgery, liver occlusion, or kidney occlusion. Under isofluorane anesthesia, liver occlusion was performed with ligatures around the portal vein and hepatic arteries while bi-lateral kidney occlusion included ligation of both renal arteries and veins. The rats were then injected with a 2 Ci bolus of I-A (1-40) into the jugular vein while blood samples were collected over a period of 60 minutes from the opposite jugular. Following TCA precipitation, both intact and degraded A levels in plasma were determined by gamma counting. Results: A clearance from subjects with a complete kidney ligation (half-life 1.6min) did not differ significantly from controls (half-life 1.4min). In contrast, A clearance differed significantly for subjects with a complete liver ligation (half-life 50min) when compared to the sham surgery. It is unlikely that this impairment was due to nonspecific systemic complications caused by the loss of liver function because after only 2.5 min there was a marked difference in the clearance of A in ahepatic versus control animals. Conclusions: These data suggest that the liver plays a highly significant role in the clearance of A and point to the importance of further study to elucidate the mechanisms by which the liver regulates peripheral A levels.