Researchers have found that, in mice, producing a single genetic defect in a molecule that "reloads" neurons to trigger one another using the neurotransmitter acetylcholine impairs the mice's ability to recognize objects or other mice.
The researchers, Marco Prado, Marc Caron, Vania Prado, and their colleagues, said their findings reveal a critical role in central nervous system (CNS) function for the component of the reloading machinery, called an acetylcholine transporter, that they knocked out. They also said their findings suggest that the mouse model will be useful in understanding how defects in neurons that use acetylcholine to trigger one another contribute to cognitive decline in such disorders as Alzheimer's disease (AD) and aging. The researchers published their finding in the September 7, 2006, issue of the journal Neuron, published by Cell Press.
To explore the role of the acetylcholine transporter, the researchers genetically modified mice to either completely lack the transporter gene or to have reduced levels of it. Such transporters normally retrieve acetylcholine that one neuron has used to trigger another and transport it to storage sacs called vesicles that are the reservoir for neurotransmitter for subsequent use. The researchers found that such transporter-deficient mice were less able to fill such vesicles with acetylcholine.
In behavioral tests, the researchers found that the mice with lower levels of the transporter were less able to learn to hang on to a rotating rod than normal mice. Mice completely lacking the transporter were totally unable to manage the task because they lacked physical endurance. Thus, wrote the researchers, those mice might be useful models for studying the effects of reduced acetylcholine release in certain neuromuscular disorders.
Both normal mice and those with reduced transporter were equally able to learn and remember to avoid a mild shock. However, the reduced-transporter m
Contact: Heidi Hardman