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
• Special Visiting Researcher - Science without Borders (UFMG Brazil, 2014-2017)
• Faculty Scholar Award (University of Western Ontario, 2013-2014)
• Senior Research Fellow National Research Council (Brazil, 1995-2008)
• John Simon Guggenheim Fellow (2005)
• IBRO Fellow (2003)
1. Ostapchenko VG, Beraldo FH, Mohammad AH, Xie YF, Hirata PHF, Magalhães AC, Lamour G, Li H, Maciejewski A, Belrose JC, Teixeira B, Fahnestock M, Ferreira ST, Cashman NR, Hajj GNM, Jackson MF, Choy WY, MacDonald JF, Martins VR, Prado VF, Prado MAM (2013) The prion protein ligand, stress-inducible phosphoprotein I (STI1), regulates amyloid-β oligomer toxicity. J Neuroscience 33(42): 16552-16564.
2. Roy A, Fields WC, Rocha-Resende C, Resende RR, Guatimosim S, Prado VF, Gros R*, Prado MAM* (2013) Cardiomyocyte-secreted acetylcholine is required for maintenance of homeostasis in the heart. FASEB J 27:5072-5082. *Corresponding authors.
3. Soares I, Caetano FA, Pinder J, Rodrigues BR, Beraldo FH, Ostapchenko VG, Durrette C, Pereira GS, Lopes MH, Queiroz-Hazarbvassanov N, Cunha IW, Sanematsu PI, Suzuki S, Bleggi-Torres LF, Schild-Poulter C, Thibault P, Dellaire G, Martins VR, Prado VF*, Prado MAM* (2013) Regulation of stress-inducible phosphoprotein 1 nuclear retention by PIAS1. Mol Cell Proteomics 12(11):3253-3270. *Corresponding authors.
4. Kolisnyk B, Al-Onaizi MA, Hirata PHF, Guzman MS, Nikolova S, Barbash S, Soreq H, Bartha R, Prado MAM*, Prado VF* (2013) Forebrain deletion of the vesicular acetylcholine transporter results in deficits in executive function, metabolic and RNA splicing abnormalities in the prefrontal cortex. J Neuroscience 33(37):14908-14920. *Corresponding authors.
5. Kolisnyk B, Guzman MS, Raulic S, Fan J, Magalhães AC, Feng G, Gros R, Prado VF*, Prado MAM* (2013) ChAT-ChR2-EYFP mice have enhanced motor endurance, but show deficits in attention and in several additional cognitive domains. J Neuroscience 33(25):10427-10438. *Corresponding authors.
6. Beraldo FH, Soares IN, Gonçalves DF, Fan J, Thomas AA, Santos TG, Mohammad AH, Roffé M, Calder MD, Nikolova S, Hajj GN, Guimaraes AL, Massensini AR, Welch I, Betts DH, Gros R, Drangova M, Watson AJ, Bartha R, Prado VF*, Martins VR*, Prado MAM* (2013) Stress-inducible phosphoprotein 1 has unique co-chaperone activity during development and regulates cellular response to ischemia via the prion protein. FASEB J 27(9):3594-3607. *Corresponding authors.
7. Martyn AC, De Jaeger X, Magalhães AC, Kesarwani K, Gonçalves DF, Raulic S, Guzman MS, Jackson MF, Izquierdo I, MacDonald JF, Prado MAM*, Prado VF* (2012) Elimination of the vesicular acetylcholine transporter in the forebrain causes hyperactivity and deficits in spatial memory and long-term potentiation. Proc Natl Acad Sci USA 109(43):17651-17656. *Corresponding authors.
8. Guzman MS, De Jaeger X, Raulic S, Souza IA, Li AX, Schmid S, Menon RS, Gainetdinov RR, Caron MG, Bartha R, Prado VF*, Prado MAM* (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; January 2012).
9. Caetano FA, Beraldo FH, Hajj GN, Guimaraes AL, Jürgensen S, Wasilewska-Sampaio AP, Hirata PH, Souza I, Machado CF, Wong DY, De Felice FG, Ferreira ST, Prado VF, Rylett RJ, Martins VR, Prado MAM (2011) Amyloid-beta oligomers increase the localization of prion protein at the cell surface. J Neurochem 117(3):538-553.
10. Beraldo FH, Arantes CP, dos Santos TG, Machado CF, Roffé M, Hajj GN, Lee KS, Magalhães AC, Caetano FA, Mancini GL, Lopes MH, Américo TA, Magdesian MH, Ferguson SSG, Linden R, Prado MAM* and Martins VR* (2011) Metabotropic glutamate receptors transduce signals for neurite outgrowth after binding of the prion protein to laminin gamma1 chain. FASEB J 25(1):265-279. *Co-senior authors. *Corresponding authors.
11. Beraldo FH, Arantes CP, dos Santos TG, Queiroz NGT, Young K, Rylett RJ, Markus RP, Prado MAM* and Martins VR* (2010) Role of α7 nicotinic acetylcholine receptor in calcium signaling induced by prion protein interaction with stress inducible protein 1. Journal of Biological Chemistry 285(47):36542-36550. *Co-senior authors. *Corresponding authors.
12. Lara L, Damasceno DD, Pires R, Gros R, Gomes ER, Gavioli M, Lima RF, Guimarães D, Lima P, Bueno Jr CR, Vasconcelos A, Roman-Campos D, Menezes CAS, Sirvente RA, Salemi VM, Mady C, Caron MG, Ferreira AJ, Brum PC, Resende RR, Cruz JS, Gomez MV, Prado VF, de Almeida AP, Prado MAM*, Guatimosim S* (2010) Dysautonomia due to reduced cholinergic neurotransmission causes cardiac remodeling and heart failure. Molecular and Cellular Biology 30(7):1746-1756. *Corresponding authors. Press Release by the University of Western Ontario.
13. 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) Endocytosis of prion protein is required for ERK 1/2 signaling induced by stress-inducible protein 1. Journal of Neuroscience 28(26):6691-6702. *Corresponding authors. Faculty of 1000 commented.
14. 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(5):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
1151 Richmond St. N.
London, ON N6A 5B7
Tel: 519-931-5777 Ext. 24888