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Nerve growth factor increases mRNA levels for the prion protein and the beta-amyloid protein precursor in developing
W C Mobley1, R L Neve, S B Prusiner
1Department of Neurology, University of California, San Francisco 94143.
Abstract:
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.
Insights
Nerve growth factor (NGF) regulates genes for prion protein (PrP) and beta-protein precursor (beta-PP) in developing hamster brains. NGF influences these genes in specific neurons, potentially impacting neurodegenerative disease pathways.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Amyloid filament deposition is a hallmark of neurodegenerative disorders like Creutzfeldt-Jakob disease and Alzheimer disease.
- Prion protein (PrP) and beta-protein precursor (beta-PP) are implicated in these conditions and are primarily expressed in brain neurons.
- The developmental regulation of PrP and beta-PP gene expression in the brain is not fully understood.
Purpose of the Study:
- To investigate the regulation of prion protein (PrP) and beta-protein precursor (beta-PP) gene expression during hamster brain development.
- To explore the potential role of nerve growth factor (NGF) in controlling PrP and beta-PP gene expression, particularly in cholinergic neurons.
Main Methods:
- Studied the ontogenesis of PrP and beta-PP messenger RNA (mRNA) in distinct brain regions of developing hamsters.
- Administered nerve growth factor (NGF) to neonatal hamsters and analyzed changes in PrP and beta-PP mRNA levels.
- Measured choline acetyltransferase activity as a marker for cholinergic neurons.
Main Results:
- Gene expression patterns for PrP and beta-PP mRNAs varied across specific brain regions during development.
- Increased PrP and beta-PP mRNA levels in the developing basal forebrain correlated with elevated choline acetyltransferase activity.
- Injections of NGF into neonatal hamsters significantly increased PrP and beta-PP mRNA levels in NGF-responsive cholinergic neuron regions.
Conclusions:
- Nerve growth factor (NGF) plays a role in regulating the gene expression of prion protein (PrP) and beta-protein precursor (beta-PP) in the developing hamster brain.
- NGF appears to influence PrP and beta-PP expression selectively in cholinergic neurons, suggesting a potential coordinate control mechanism.
- Further research is needed to confirm the selective action of exogenous and endogenous NGF on PrP and beta-PP gene expression in developing forebrain cholinergic neurons.