Proceedings of the National Academy of Sciences · 2001 · 338 citations · 34 references
Life SciencesNeurobiologyNeuroscienceDevelopmental NeuroscienceMolecular NeuroscienceNeurodegenerationAlzheimer DiseaseNeurodegenerative DiseasesNeurodegenerative DisordersNeuroprotectionNeurotransmissionSynaptic TransmissionAge-related Brain ChangesAge-related Neurodegenerative MechanismsCholinergic Synaptic DysfunctionNerve Growth Factor SignalingRetrograde Axonal TransportRetrograde Transport In NeuronsRodent NeurodegenerationSynaptic Loss
Age-related degeneration of basal forebrain cholinergic neurons (BFCNs) contributes to cognitive decline in Alzheimer's disease and Down's syndrome. With aging, the partial trisomy 16 (Ts65Dn) mouse model of Down's syndrome exhibited reductions in BFCN size and number and regressive changes in the hippocampal terminal fields of these neurons with respect to diploid controls. The changes were associated with significantly impaired retrograde transport of nerve growth factor (NGF) from the hippocampus to the basal forebrain. Intracerebroventricular NGF infusion reversed well established abnormalities in BFCN size and number and restored the deficit in cholinergic innervation. The findings are evidence that even BFCNs chronically deprived of endogenous NGF respond to an intervention that compensates for defective retrograde transport. We suggest that age-related cholinergic neurodegeneration may be a treatable disorder of failed retrograde NGF signaling.
34
Alzheimer's Disease and Senile Dementia: Loss of Neurons in the Basal Forebrain
PJ Whitehouse, DL Price, R. G. Struble et al. · Science · 1982 · 3.6K citations
mouse brain in stereotaxic coordinates
Keith B.J. Franklin, George Paxinos · 1997 · 3.1K citations
A mouse model for Down syndrome exhibits learning and behaviour deficits
Roger H. Reeves, Nicholas G. Irving, Timothy H. Moran et al. · Nature Genetics · 1995 · 914 citations