Coaccumulation of calcium and beta-amyloid in the thalamus after transient middle cerebral artery occlusion in rats.
Transient occlusion of the middle cerebral artery (MCAO) in rats leads to abnormal accumulation of beta-amyloid (Abeta) peptides in the thalamus. This study investigated the chemical composition of these deposits. Adult male human beta-amyloid precursor protein (APP) overexpressing (hAPP695) rats and their wild-type littermates were subjected to transient MCAO for 2 h or sham operation. After 26-week survival time, histological examination revealed an overlapping distribution pattern for rodent and human Abeta in the thalamus of hAPP695 rats subjected to MCAO. X-ray microanalysis showed that the deposits did not contain significant amount of iron, zinc, or copper typical to senile plaques. In contrast, the deposit both in hAPP695 and non-transgenic rats contained calcium and phosphorus in a ratio (1.28+/-0.15) characteristic to hydroxyapatites. Alizarin red staining confirmed that calcium coaccumulated in these Abeta deposits. It is suggested that APP expression is induced by ischemic insult in cortical neurons adjacent to infarct, which in turn is reflected as increased release of Abeta peptides by their corticothalamic axon endings. This together with insufficient clearance or atypical degradation of Abeta peptides lead to dysregulation of calcium homeostatis and coaccumulation in the thalamus.
Mäkinen
Susanna
S
Department of Neurology, University of Kuopio, Kuopio, Finland.
van Groen
Thomas
T
Clarke
Jared
J
Thornell
Anders
A
Corbett
Dale
D
Hiltunen
Mikko
M
Soininen
Hilkka
H
Jolkkonen
Jukka
J
D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D030801:Animals, Genetically Modified; D000880:Anthraquinones; D002545:Brain Ischemia / Q000473:pathology; D002118:Calcium / Q000378:metabolism*; D004396:Coloring Agents; D004577:Electron Probe Microanalysis; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007150:Immunohistochemistry; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism*; D008026:Ligation; D008297:Male; D008855:Microscopy, Electron, Scanning; D020768:Middle Cerebral Artery / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344; D013788:Thalamus / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D000880:Anthraquinones; D004396:Coloring Agents; C010078:alizarin; D002118:Calcium