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Object recognition memory and cholinergic parameters in mice expressing human presenilin 1 transgenes
E Vaucher1, P Fluit, M A Chishti
1Douglas Hospital Research Center, Department of Psychiatry, McGill University, Verdun, Québec H4H 1R3, Canada.
Experimental Neurology
|June 14, 2002
Summary
Mutant presenilin 1 (PS1) gene expression in mice impairs object memory, suggesting a link between PS1 mutations and cognitive decline in Alzheimer disease (AD) without altering cholinergic neurochemistry.
Area of Science:
- Neuroscience
- Genetics
- Pathophysiology
Background:
- Autosomal dominant Alzheimer disease (AD) often results from presenilin 1 (PS1) gene mutations.
- PS1 mutations affect beta-amyloid precursor protein processing, increasing amyloid-beta(1-42) deposition.
- Cognitive deficits in AD correlate with cholinergic system degeneration.
Purpose of the Study:
- To investigate the effects of mutant human PS1 (L286V) on learning and memory.
- To assess the impact of mutant PS1 on cholinergic neurochemistry in transgenic mice.
Main Methods:
- Generated transgenic mice expressing wild-type (wt) or L286V mutant human PS1.
- Evaluated sensorimotor activity and object memory.
- Measured choline acetyltransferase activity and muscarinic/nicotinic receptor binding densities in brain regions.
Main Results:
- L286V PS1 transgenic mice showed reduced sensorimotor activity and impaired object memory.
- No significant alterations in choline acetyltransferase activity were observed.
- Cholinergic receptor binding site densities remained unchanged across all groups.
Conclusions:
- Overexpression of mutated PS1 induces subtle object memory deficits.
- These memory impairments occur independently of changes in cholinergic neurochemistry.