A team of researchers at The University of Western Ontario has demonstrated that elimination of one of the neurotransmitters in the part of the brain associated with Parkinson's disease may improve brain function without major adverse effects. The research is published November 8 in the online, open-access journal PLoS Biology.
Marco Prado, Vania Prado and a team of researchers at the Schulich School of Medicine & Dentistry's Robarts Research Institute used unique genetically modified mice to study the function of specific neurotransmitters in the striatum, which is the region of the brain affected in Parkinson's, Huntington's, and other motor diseases. They were particularly interested in the neurotransmitter acetylcholine, and what effect it has on brain function.
The researchers used state-of-the-art genetic techniques to selectively eliminate the secretion of acetylcholine in striatal neurons. These neurons release acetylcholine, but they also secrete a neurotransmitter called glutamate. Prado and his colleagues found that they could get rid of acetylcholine secretion without disturbing brain function "The surprise was that these neurons in the striatum actually do two different jobs. This suggests that perhaps glutamate secreted by these neurons plays a more important role in this part of the brain than was originally suspected," says Marco Prado.
The researchers also discovered a unique relationship between acetylcholine, glutamate and dopamine: the elimination of acetylcholine secretion boosted the actions of dopamine. This may have important applications to Parkinson's disease because increased function of dopamine has been previously shown to improve motor symptoms in the disease.
Prado says the next steps in their research will be to eliminate acetylcholine secretion in Parkinson's disease mouse models to see if there are improvements in the motor symptoms. "We suspect there will be improvement because in Parkinson's disease, in addition to the loss of dopamine, this group of neurons that secrete acetylcholine becomes abnormally hyperactive," he says. The hope is to eventually produce a drug to block acetylcholine release selectively in the striatum. If the researchers' suspicions are correct, this should help in Parkinson's disease by blocking the activity of these neurons without having any overall negative effects on brain and motor function.
Funding: This work was supported by the Canadian Institutes of Health Research (CIHR), Canadian Foundation for Innovation (CFI), and the Ontario Research Fund (ORF). MGC received support from the NIH. XDeJ, BMC, and IAS received PhD fellowships from CAPES (Brazil). IAS also received support from the Emerging Leaders of America Program (ELAP) from the Department of Foreign Affairs and International Trade (Canada). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Citation: Guzman MS, De Jaeger X, Raulic S, Souza IA, Li AX, et al. (2011) Elimination of the Vesicular Acetylcholine Transporter in the Striatum Reveals Regulation of Behaviour by Cholinergic-Glutamatergic Co-Transmission. PLoS Biol 9(11): e1001194. doi:10.1371/journal.pbio.1001194
Journal
PLoS Biology