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Nerve growth factor does not influence the expression of beta amyloid precursor protein mRNA in rat brain: in vivo
G Forloni1, R Del Bo, N Angeretti
1Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
Abstract:
We investigated the effect of NGF on amyloid precursor protein (APP) mRNA levels in the rat septal/nucleus basalis system. Total APP mRNA and APP 695 mRNA were determined in basal forebrain primary cell cultures exposed acutely and chronically to NGF (150-300 ng/ml) and, in vivo, in the septal area and striatum of rat pups after multiple intracerebroventricular injections of NGF. The trophic factor was able to affect cholinergic neurons in both paradigms, as evidenced by the significant increase of choline acetyltransferase (ChAT) activity induced by NGF in cell cultures (+80%) and in the striatum (+240%) of rat pups. In spite of this effect, no significant change of APP mRNA expression was observed in neuronal cultures and brain tissues. These data indicate that the neurotrophic effect of NGF on forebrain cholinergic neurons is not always associated with an alteration of APP expression.
Insights
Nerve growth factor (NGF) enhances cholinergic neuron activity but does not alter amyloid precursor protein (APP) mRNA levels in rat brain models. This suggests NGF
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- Amyloid precursor protein (APP) is implicated in neurodegenerative diseases.
- Nerve growth factor (NGF) plays a crucial role in neuronal survival and function, particularly for cholinergic neurons.
- The relationship between NGF's neurotrophic effects and APP expression is not fully understood.
Purpose of the Study:
- To investigate the impact of NGF on amyloid precursor protein (APP) mRNA expression in rat basal forebrain cholinergic neurons.
- To determine if NGF-induced neurotrophic effects correlate with changes in APP mRNA levels.
- To explore the effects of NGF in both in vitro cell cultures and in vivo rat models.
Main Methods:
- Primary basal forebrain cell cultures and rat pups were used as experimental models.
- Cells and brain tissues (septal area, striatum) were exposed to NGF acutely and chronically.
- Quantification of total APP mRNA and APP 695 mRNA levels was performed.
- Choline acetyltransferase (ChAT) activity was measured to assess NGF's effect on cholinergic neurons.
Main Results:
- NGF significantly increased choline acetyltransferase (ChAT) activity in both cell cultures (+80%) and rat pup striatum (+240%), confirming its neurotrophic effect on cholinergic neurons.
- Despite the observed neurotrophic effects, no significant changes in total APP mRNA or APP 695 mRNA expression were detected in neuronal cultures or brain tissues.
- These findings indicate a dissociation between NGF's neurotrophic actions and APP gene expression.
Conclusions:
- The neurotrophic effects of NGF on forebrain cholinergic neurons are not consistently linked to alterations in APP mRNA expression.
- NGF may influence cholinergic neuron function through pathways independent of APP gene regulation.
- Further research is needed to elucidate the complex interplay between neurotrophic factors and APP metabolism in the brain.