Brain suppression of acetylcholine release
Principal Investigator
Project Goals
Project Summary
Early cognitive symptoms of Alzheimer's disease can be improved by drugs that slow the breakdown of an important brain messenger called acetylcholine. Researchers have known that neurons that secrete acetylcholine are vulnerable in Alzheimer's disease, but so far, they have been unable to understand specifically how a lack of acetylcholine influences behavior. However, recent advances in scientific methodologies make it possible to generate mouse models that have specific mutations. Dr. Prado has hypothesized that these methodologies can now be used to selectively impair or decrease acetylcholine secretion in certain brain regions of the mouse. Certain behaviors can now be studied in these mice and their performance correlated with the levels of acetylcholine secretion in different brain regions. This research will provide fundamental knowledge on how a deficit of acetylcholine contributes to some of the symptoms associated with Alzheimer's disease.
Publications
Prado VF, Martins- Silva C, de Castro BM, Lima RF, Barros DM, Amaral E, Ramsey AJ, Sotnikova TD, Ramirez MR, Kim HG, Rossato JI, Koenen J, Quan H, Cota VR, Moraes MF, Gomez MV, Guatimosim C, Wetsel WC, Kushmerick C, Pereira GS, Gainetdinov RR, Izquierdo I, Caron MG, Prado MAM (2006) Mice deficient for the vesicular acetylcholine transporter are myasthenic and have deficits in object and social recognition. Neuron 51: 601-612. 
Ribeiro FM, Black SAG, Prado VF, Rylett RJ, Ferguson ssG, Prado MAM (2006) The ins and outs of the high affinity choline transporter CHT1. Journal of Neurochemistry 97: 1-12.
Ribeiro FM, Ferreira LT, Marion S, Fontes S, Gomez MV, Ferguson ssG, Prado MAM, Prado VF. Sec14-like protein 1 interacts with cholinergic transporters. Neurochemistry International 50: 356-364.
Guidine PA, Rezende GH, Queiroz CM, Mello LE, Prado VF, Prado MAM, Pereira GS, Moraes MF (2008) Vesicular acetylcholine transporter knock-down mice are more susceptible to pilocarpine induced status epilepticus. Neuroscience Letters 436: 201-420.
de Castro, B.M.; Pereira, G.S.; Magalha~es, V.; Rossato, J.I.; de Jaeger, X.; Martins-Silva, C.; Leles, B.; Lima, P.; Gomez, M.V.; Gainetdinov, R.R.; Caron, M.G.; Izquierdo, I.; Cammarota, M.; Prado, V.F.; Prado, M.A.M. (2008) Reduced expression of the vesicular acetylcholine transporter causes learning deficits in mice. Genes, Brain and Behavior, 2009 Feb;8(1):23-35. Epub 2008 Sep 6.
First published on: June 11, 2008
Last modified on: December 22, 2024