(Cross Appointment with Physiology and Pharmacology
and Robarts Research Institute)
Location: Robarts Research Institute
The Unviersity of Western Ontario
P.O. Box 5015, 100 Perth Drive
London, ON N6A 5K8
Phone: 519-661-2111 Ext. 86827
Visit: Dr. Prado's lab
The focus of my research is the cholinergic system. During aging and age-related dementia such as Alzheimer’s, Huntington’s and Parkinson’s disease, altered release of the cholinergic transmitter acetylcholine seems to underlie some of the cognitive and behavioral deficits observed in patients. Hence we have generated a collection of genetically modified mice to test the role of cholinergic transporters for maintaining the synthesis and storage of acetylcholine in nerve terminals. This research test the possibility that cholinergic transporters can function as drug targets to improve acetylcholine release, an important therapeutic approach in dementia, myasthenia and other disturbances of the cholinergic system. Also, we are developing novel recombinant proteins that are active on ion channels and have potential to be used as therapeutic drugs. These recombinant toxins, originally identified in the venom of a Brazilian spider, have been shown to be effective in controlling pain and cardiac arrhythmia in animal models.
De Castro, B; De Jaeger, X; Martins-Silva, C.; Lima, R.F.; Amaral, E.; Menezes, C.; Lima, P.; Neves, C.M.L; Gould, T.W.; Welch, I; Kushmeric, C.; Guatimosim, C.; Izquierdo,I.; Cammarota, M.; Rylett, R.J.; Gomez, M.V.; Caron, M.G.; Oppenheim, R.W.; Prado, M.A.M.; Prado, V.F*. (2009) The vesicular acetylcholine transporter is required for neuromuscular development and function. Molecular and Cellular Biology 29: 5238-50. *co-senior authors
de Castro BM, Pereira GS, Magalhães V, Rossato JI, De Jaeger X, Martins-Silva C, Leles B, Lima P, Gomez MV, Gainetdinov RR, Caron MG, Izquierdo I, Cammarota M,Prado VF, Prado MA. Reduced expression of the vesicular acetylcholine transporter causes learning deficits in mice. Genes Brain Behav. 8:23-35 (2009).
Souza AH, Ferreira J, Cordeiro Mdo N, Vieira LB, De Castro CJ, Trevisan G, Reis H, Souza IA, Richardson M, Prado MA, Prado VF, Gomez MV. Analgesic effect in rodents of native and recombinant Ph alpha 1beta toxin, a high-voltage-activated calcium channel blocker isolated from armed spider venom. Pain. 15;140(1):115-26 (2008).
Ribeiro FM, Ferreira LT, Marion S, Fontes S, Gomez MV, Ferguson SS, Prado MA, Prado VF. SEC14-like protein 1 interacts with cholinergic transporters. Neurochem Int. 50:356-64 (2007).
Martins-Silva C, Ferreira LT, Cyr M, Koenen J, Fernandes DR, Carvalho NR, Ribeiro CB, Marion S, Chavez-Olortegui C, Prado MA, Prado VF. A rat homologue of CED-6 is expressed in neurons and interacts with clathrin. Brain Res. 1119:1-12 (2006).
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 MA. Mice deficient for the vesicular acetylcholine transporter are myasthenic and have deficits in object and social recognition. Neuron 51(5):601-12 (2006).