Reversal of long-term dendritic spine alterations in Alzheimer disease models
Open Access
- 29 September 2009
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 106 (39), 16877-16882
- https://doi.org/10.1073/pnas.0908706106
Abstract
Synapse loss is strongly correlated with cognitive impairment in Alzheimer's disease (AD). We have previously reported the loss of dendritic spines and the presence of dystrophic neurites in both the hippocampi of transgenic mice overexpressing amyloid precursor protein (APP) and in the human brain affected with AD. In the studies reported here we have asked whether the acute alterations in dendritic spines induced by Aβ, as well as the chronic loss of spine density seen in hAPP transgenic mice, are reversible by treatments that restore the cAMP/PKA/CREB signaling pathway or proteasome function to control levels. The results show that both rolipram and TAT-HA-Uch-L1 restore spine density to near control conditions, even in elderly mice. The results suggest that changes in dendritic structure and function that occur after Aβ elevation are reversible even after long periods of time, and that one could envision therapeutic approaches to AD based on this restoration that could work independently of therapies aimed at lowering Aβ levels in the brain.Keywords
This publication has 42 references indexed in Scilit:
- AMPAR Removal Underlies Aβ-Induced Synaptic Depression and Dendritic Spine LossNeuron, 2006
- Amyloid β peptide adversely affects spine number and motility in hippocampal neuronsMolecular and Cellular Neuroscience, 2006
- Ubiquitin Hydrolase Uch-L1 Rescues β-Amyloid-Induced Decreases in Synaptic Function and Contextual MemoryCell, 2006
- Pathways towards and away from Alzheimer's diseaseNature, 2004
- The Amyloid Hypothesis of Alzheimer's Disease: Progress and Problems on the Road to TherapeuticsScience, 2002
- Multicolor “DiOlistic” Labeling of the Nervous System Using Lipophilic Dye CombinationsNeuron, 2000
- Block of LTP in rat hippocampus in vivo by β-amyloid precursor protein fragmentsNeuroReport, 1997
- Increased amyloid-β42(43) in brains of mice expressing mutant presenilin 1Nature, 1996
- Dendrites, dementia and the down syndromeBrain & Development, 1989
- The septo-hippocampal pathway in patients suffering from senile dementia of Alzheimer's type. Evidence for neuronal plasticity?Neuroscience Letters, 1987