Nerve growth factor increases mRNA levels for the prion protein and the beta-amyloid protein precursor in developing hamster brain.
Deposition of amyloid filaments serves as a pathologic hallmark for some neurodegenerative disorders. The prion protein (PrP) is found in amyloid of animals with scrapie and humans with Creutzfeldt-Jakob disease; the beta protein is present in amyloid deposits in Alzheimer disease and Down syndrome patients. These two proteins are derived from precursors that in the brain are expressed primarily in neurons and are membrane bound. We found that gene expression for PrP and the beta-protein precursor (beta-PP) is regulated in developing hamster brain. Specific brain regions showed distinct patterns of ontogenesis for PrP and beta-PP mRNAs. The increases in PrP and beta-PP mRNAs in developing basal forebrain coincided with an increase in choline acetyltransferase activity, raising the possibility that these markers might be coordinately controlled in cholinergic neurons and regulated by nerve growth factor (NGF). Injections of NGF into the brains of neonatal hamsters increased both PrP and beta-PP mRNA levels. Increased PrP and beta-PP mRNA levels induced by NGF were confined to regions that contain NGF-responsive cholinergic neurons and were accompanied by elevations in choline acetyltransferase. It remains to be established whether or not exogenous NGF acts to increase PrP and beta-PP gene expression selectively in forebrain cholinergic neurons in the developing hamster and endogenous NGF regulates expression of these genes.
Mobley
W C
WC
Department of Neurology, University of California, San Francisco 94143.
Neve
R L
RL
Prusiner
S B
SB
McKinley
M P
MP
D000682:Amyloid / Q000235:genetics*; D016564:Amyloid beta-Protein Precursor; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism; D007562:Creutzfeldt-Jakob Syndrome / Q000235:genetics; D006224:Cricetinae; D005786:Gene Expression Regulation; D006801:Humans; D009414:Nerve Growth Factors / Q000494:pharmacology*; D018620:PrPSc Proteins; D011498:Protein Precursors / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism*; D012608:Scrapie / Q000235:genetics; D014764:Viral Proteins / Q000235:genetics*
D000682:Amyloid; D016564:Amyloid beta-Protein Precursor; D009414:Nerve Growth Factors; D018620:PrPSc Proteins; D011498:Protein Precursors; D012333:RNA, Messenger; D014764:Viral Proteins