Increased amyloid protein precursor and apolipoprotein E immunoreactivity in the selectively vulnerable hippocampus following transient forebrain ischemia in gerbils.
The postischemic time course of amyloid protein precursor (APP), beta-amyloid protein (beta-AP), and apolipoprotein E (APO-E) immunoreactivity were examined in comparison to neuronal necrosis in the selectively vulnerable hippocampal CA1 region of gerbils subjected to 10 min of bilateral carotid occlusion-induced forebrain ischemia. Loss of 90% of the CA neurons occurred between 24 and 72 h after ischemia, after which no further neuronal necrosis was observed. At 24 h postischemia, there was a decrease in APP and beta-AP immunostaining in the CA1 region. However, beginning at 2 days, there was a dramatic increase in the staining for both proteins. This coincided with a progressive increase in the expression of APO-E and glial fibrillary acidic protein (GFAP) staining between Days 2 and 6, indicative of an activation of astrocytic protein synthesis. Each of the immunocytochemical markers also increased in the less vulnerable CA3 region. However, the peak increase in that region was much less than that in CA1 and, by 7 days, only the GFAP staining remained significantly above the sham level. It has been shown that the E4 isoform of APO-E, when oxidized, avidly binds to beta-AP and thus increases the likelihood of co-beta-AP/APO-E deposition. Therefore, it is postulated that the increased levels of amyloid proteins coincident with an increased production of APO-E in response to ischemic neuronal necrosis may provide conditions that are favorable for the postischemic formation of amyloid deposits.
Hall
E D
ED
Upjohn Company, Kalamazoo, Michigan 49001, USA.
Oostveen
J A
JA
Dunn
E
E
Carter
D B
DB
D016564:Amyloid beta-Protein Precursor / Q000032:analysis*; D000818:Animals; D001057:Apolipoproteins E / Q000032:analysis*; D005849:Gerbillinae; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000473:pathology; D008297:Male
D016564:Amyloid beta-Protein Precursor; D001057:Apolipoproteins E; D005904:Glial Fibrillary Acidic Protein