Marco Antonio Maximo Prado, Scientist
Why I Became a Scientist
I attended Pharmacy school and when studying Physiology, and then Pharmacology, I became intrigued by how neurons communicate with each other and with target organs. The possibility to answer fundamental questions on neuronal communication that can provide novel treatments for diseases has driven my interests in research since then.
Communication between cells is the major business of the nervous system. We are interested in how neuronal communication can be manipulated to treat or prevent neurological and cardiovascular disorders. To achieve this goal we use a combination of molecular, cellular, pharmacological and behavioral approaches, as well as genetically modified mice, to understand how chemical messengers regulate many distinct physiological programs. Of particular interest to us is the role of cholinergic synapses that release the chemical mediator acetylcholine, in Alzheimer’s disease and in learning and memory. We are also interested in how cholinergic neurotransmission in the peripheral nervous system may be targeted to improve cardiac dysfunction. Finally, we have a strong research program aimed to understand transmissible spongiform encephalopathy, or prion diseases, such as “mad cow disease”. A long-term objective of my research program is to discover ways to manipulate chemical communication to provide novel pharmacological targets to treat these diseases.
Research Questions and Disease Implications
The prion protein has emerged as a major player to organize communication in the brain. The protein can change shape and this causes disease. Recent work has provided novel evidence for a role of prion protein in Alzheimer’s disease. However, how signalling by the prion protein influences neurological disorders is unknown.
Our research will uncover fundamental mechanisms by which neurons use the prion protein to communicate and may provide novel ways to treat Alzheimer’s and prion diseases.
In Alzheimer’s disease the chemical messenger acetylcholine is decreased and neurons are unable to maintain normal levels of acetylcholine secretion. How this affects cognitive processing in Alzheimer’s disease? How acetylcholine regulates hippocampal function?
This work will provide novel information on how acetylcholine regulates brain functions. We will also learn if it is possible to manipulate the machinery used to secrete acetylcholine to increase its activity in the brain.
Acetylcholine is the major chemical messenger regulating autonomic functions. Cholinergic neurons regulate most of our bodily functions, but in certain diseases such as diabetes and dysautonomy these neurons cannot function well. What happens when neurons that control the heart go awry? How the autonomic system shapes heart function in the long-term?
This research has started to uncover novel mechanisms that regulate long-term activity of the heart and has implications to develop novel treatments for heart failure.
• Pharmacy; MSc Biochemistry; PhD Biochemistry; Diploma Cell Biology
• UFMG; McGill University; Duke University
• Senior Research Fellow National Research Council (Brazil, 1995-2008)
• IBRO Fellow (2003)
• John Simon Guggenheim Fellow (2005)
1. Guzman, M.S., De Jaeger, X., Raulic, S., Souza, I.A., Li, A.X., Schmid S., Menon, R.S., Gainetdinov, R.R., Caron, M.G., Bartha, R., Prado, V.F.*, Prado, M.A.M.* (2011) Elimination of the vesicular acetylcholine transporter in the striatum reveals regulation of behavior by cholinergic-glutamatergic co-transmission. PLoS Biol. 9, (11):e1001194. *Corresponding authors. (Press release by UWO and PLoS Biology; commented in Nature Reviews of Neuroscience; Jan 2012).
2. Caetano F.A., Beraldo F.H., Hajj G.N., Guimaraes A.L., Jürgensen S., Wasilewska-Sampaio A.P., Hirata P.H., Souza I., Machado C.F., Wong D.Y., De Felice F.G., Ferreira S.T., Prado V.F., Rylett R.J., Martins V.R., Prado M.A.M. (2011) Amyloid-beta oligomers increase the localization of prion protein at the cell surface. J. Neurochem. 117(3):538-553.
3. Beraldo, F.H., Arantes , C.P., dos Santos, T.G., Queiroz, N.G.T., Young, K., Rylett R.J., Markus, R.P., Prado*, M.A.M. and Martins*, V.R. (2010) The role of α7 nicotinic acetylcholine receptor in calcium signaling induced by prion protein interaction with stress inducible protein 1. *Co-senior authors. Journal of Biological Chemistry 285: 36542-36550. *Corresponding authors.
4. Lara, L., Damasceno, D.D., Pires, R., Gros R., Gomes, E.R., Gavioli, M., Lima, R.F., Guimarães D., Lima, P., Bueno Jr, C.R. Vasconcelos, A., Roman-Campos, D. Menezes, C.A.S., Sirvente, R.A., Salemi, V.M., Mady, C., Caron, M.G., Ferreira, A.J., Brum, P.C., Resende, R.R., Cruz, J.S., Gomez, M.V., Prado, V.F. de Almeida, A.P., *Prado, M.A.M, *Guatimosim, S. (2010) Dysautonomia due to reduced cholinergic neurotransmission causes cardiac remodeling and heart failure. Molecular and Cellular Biology 30: 1746-1756. *Corresponding authors. Press Release by the University of Western Ontario.
5. Caetano FA, Lopes MH, Haijj GNM, Machado CF, Arantes CP, Magalhães AC, Vieira MPB Américo TA, Massensini AR, Priola SA, Vorberg I, Gomez MV, Linden R, Prado VF, Martins VR*, Prado MAM* (2008) Prion protein endocytosis is required for ERK 1/2 signaling induced by stress-inducible protein. Journal of Neuroscience 28: 6691-6702. *Corresponding authors. Faculty of 1000 commented.
6. 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. *Corresponding authors. [Preview of this article by Thomas S. Hnasko and Robert H. Edwards, Synaptic Vesicles: Half Full or Half Empty? Neuron 51, 523-524; discussed in the Alzheimer’s Association Forum]
Robarts Research Institute
The University of Western Ontario
100 Perth Drive
London, ON N6A 5K8
Tel: 519-931-5777 Ext. 24888