Induction of apolipoprotein E mRNA in the hippocampus of the gerbil after transient global ischemia.
B/A4 is the major component of brain amyloid plaque, one of the hallmarks of Alzheimer's disease (AD). B/A4 is a product of proteolytic processing of its precursor, the Alzheimer amyloid precursor protein (APP). Recently, apolipoprotein E (APO-E) has also been shown to be associated with Alzheimer's disease pathology because it is localized to plaques and tangles, and the gene encoding one of the isoforms of APO-E (E4) is associated with late-onset familial and sporadic AD. In addition, APO-E exhibits high affinity for binding to the B-peptide (B/A4). In this study, we have investigated changes in the steady state levels of APP, APO-E, and the astrocyte-specific marker, glial fibrillary acidic protein (GFAP) mRNA in the gerbil hippocampal CA1 region after a 10-min period of bilateral carotid occlusion-induced forebrain ischemia. Following this insult, we observed a loss of 90% of the CA1 neurons by 72 h post-ischemia. The mRNA levels on day 1 through day 7 post-ischemia were quantitated using an image analyzer. There was an increase in the transcription of APO-E and GFAP mRNAs, with the levels of APO-E mRNA being the highest (3-fold increase on day 7 post-ischemia) (P < 0.005). However, we did not see an increase in APP mRNA. In a parallel study [Hall, E.D. et al., Exp. Neurol., 135(1995) 17-27], we have also seen an increase in levels of APO-E and GFAP protein measured by immunocytochemistry. However, in contrast to the lack of an increase in APP mRNA, immunocytochemical measurement of APP did show an increase, perhaps due to delayed translation of previously formed mRNA. We suggest that neuronal injury or insult results in the induction of certain genes (and, therefore, protein synthesis) in the surrounding reactive astrocytes, and these proteins may contribute to post-injury amyloidogenesis.
Ali
S M
SM
Central Nervous System Diseases Research, Upjohn Co., Kalamazoo, MI 49001, USA.
Dunn
E
E
Oostveen
J A
JA
Hall
E D
ED
Carter
D B
DB
D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics*; D015415:Biomarkers; D015342:DNA Probes; D005849:Gerbillinae; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D017403:In Situ Hybridization; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D016548:Prosencephalon / Q000098:blood supply*; D012333:RNA, Messenger / Q000096:biosynthesis*; D012016:Reference Values
D016564:Amyloid beta-Protein Precursor; D001057:Apolipoproteins E; D015415:Biomarkers; D015342:DNA Probes; D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger