Vania F. Prado, PhD

Vania F. Prado, Scientist

Why I Became a Scientist

As a child I always wanted to know how things work.  When I went to Dentistry School I got really fascinated by the studies on how cells work, how they communicate, how they can differentiate to make different tissues and by the fact that there were still so many unanswered questions.  So, I decided to become a scientist to investigate different aspects of cellular function, to better understand mechanisms of diseases and find new treatments.

Research Summary

Dr. Vania Prado’s main interest is the cholinergic system. Altered release of the cholinergic transmitter acetylcholine seems to underlie some of the cognitive and behavioural deficits observed in patients with age-related dementia. She has generated a collection of genetically modified mice to test the role of cholinergic transporters for maintaining synthesis and storage of acetylcholine in nerve terminals. The aim of this research is to test the possibility of using cholinergic transporters as drug targets to improve acetylcholine release, an important therapeutic approach in dementia (such as Alzheimer’s, Huntington’s and Parkinson’s disease), myasthenia and other disturbances of the cholinergic system.

Research Questions and Disease Implications

During aging and more predominantly, in patients with Alzheimer’s disease, cholinergic neurons are unable to maintain normal levels of acetylcholine release. 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.  This information would be important to improve understanding of mechanisms underlining cognitive deficits observed in aging and neurodegenerative diseases such as Alzheimer’s.

Attempts to increase cholinergic tone have relied mainly in preserving ACh for long periods in the synapse by using cholinesterase inhibitors. Could cholinergic transporters be a target to regulate the amount of ACh stored and released by cholinergic nerve terminals?  

We will learn whether it is possible to manipulate the machinery used to secrete acetylcholine to increase its activity in the brain. This information may give us new targets to develop therapeutic drugs to boost cholinergic tone and would be valuable in the treatment of diseases such as myasthenia gravis, Alzheimer’s disease, Lewy Body Dementia, etc. These new drugs would have the advantage of increasing ACh release only during nerve activity (similar to the physiological process) and we expect they would cause (or cause much less) collateral effect when compared to the cholinesterase inhibitors currently available.

It has been shown that cholinergic neurons in the brain can also release other neurotransmitters (in addition to acetylcholine).  How each one of the neurotransmitters released by cholinergic neurons (in many cases, acetylcholine and glutamate) regulates behavioral functions?

We will be able to tell apart the specific physiological roles of acetylcholine and its co-transmitted neurotransmitter in different areas of the brain. This information may open up new avenues in the search of more effective treatments for behavioral changes associated with diseases such as Alzheimer’s, Parkinson’s, Huntington’s, etc.


• Dentistry; PhD Biochemistry


• UFMG (Brazil) ; McGill University; Duke University


• Junior  Research Fellow National Research Council (Brazil, 1994-2003)
• Senior Research Fellow National Research Council (Brazil, 2003-2008)


1. Roy A, Guatimosim S, Prado VF, Gros R, Prado MAM. Cholinergic activity as a new target in diseases of the heart. Mol Med. 20(1):527-537 (2015).

2. Ostapchenko VG, Beraldo FH, Mohammad AH, Xie YF, Hirata P, Magalhães AC, Lamour G, Li H, Maciejewski A, Belrose JC, Teixeira BL, Fahnestock M, Ferreira ST, Cashman NR, Hajj GN, Jackson MF, Choy WY, MacDonald JF, Martins VR, Prado VF, Prado MAM. The prion protein ligand, stress-inducible phosphoprotein 1 (STI1), regulates amyloid-β oligomer toxicity. J Neurosci. 33(42):16552-16564 (2013).

3. Roy A, Fields WC, Rocha-Resende C, Resende RR, Guatimosim S, Prado VF, Gos R, Prado MAM. Cardiomyocyte-secreted acetylcholine is required for maintenance of homeostasis in the heart. FASEB J. 27:5072-5082 (2013).

4. Soares IN, Caetano FA, Pinder J, Rodrigues BR, Beraldo FH, Ostapchenko VG, Durette C, Pereira GS, Lopes MH, Queiroz-Hazarbassanov N, Cunha IW, Sanematsu PI, Suzuki S, Bleggi-Torres LF, Schild-Poulter C, Thibault P, Dellaire G, Martins VR, Prado VF, Prado MAM. Regulation of stress-inducible phosphoprotein 1 nuclear retention by protein inhibitor of activated STAT PIAS1. Mol Cell Proteomics. 12(11):3253-3270 (2013).

5. Kolisnyk B, Al-Onaizi MA, Hirata PH, Guzman MS, Nikolova S, Barbash S, Soreq H, Bartha R, Prado MAM, Prado VF. Forebrain deletion of the vesicular acetylcholine transporter results in deficits in executive function, metabolic, and RNA splicing abnormalities in the prefrontal cortex. J Neurosci. 33(37):14908-14920 (2013).

6. Kolisnyk B, Guzman MS, Raulic S, Fan J, Magalhães AC, Feng G, Gros R, Prado VF, Prado MAM. ChAT-ChR2-EYFP mice have enhanced motor endurance but show deficits in attention and several additional cognitive domains. J Nuerosci. 33(25):10427-10438 (2013).

7. Beraldo FH, Soares IN, Goncalves DR, Fan J, Thomas AA, Santos TG, Mohammad AH, Roffe M, Calder MD, Nikolova S, Hajj G, Guimarães AL, Massensini AR, Welch I, Betts DH, Gros R, Drangova M, Watson AJ, Bartha R, Prado VF, Martins VR, Prado MAM. Stress-inducible phosphoprotein 1 has unique co-chaperone activity during development and regulates cellular response to ischemia via the prion protein. FASEB J. 27:3594-3607 (2013).

8. Ostapchenko VG, Beraldo FH, Guimarães AL, Mishra S, Guzman MS, Fan J, Martins VR, Prado VF, Prado MAM. Increased prion protein processing and expression of metabotropic glutamate receptor 1 in a mouse model of Alzheimer's disease. J Neurochem. 127(3):415-425 (2013).

9. Guzman MS, De Jaeger X, Drangova M, Prado MAM, Gros R, Prado VF. Mice with selective elimination of striatal acetylcholine relase are lean, show altered energy homeostasis and changed sleep/wake cycle. J Neurochem. 124(5):658-669 (2013).

10. Prado VF, Roy A, Kolisnyk B, Gros R, Prado MAM. Regulation of cholinergic activity by the vesicular acetylcholine transporter. Biochem J. 450(2):265-274 (2013).

11. De Jaeger X, Cammarota M, Prado MAM, Izquierdo I, Prado VF, Pereira GS. Decreased acetylcholine release delays the consolidation of object recognition memory. Behav Brain Res. 238:62-68 (2013).

12. Martyn AC, De Jaeger X, Magalhães AC, Kesarwani R, Goncalves DF, Raulic S, Guzman MS, Jackson MF, Izquierdo I, MacDonald JF, Prado MAM, Prado VF. 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 (2012).

13. Roy A, Lara A, Guimarães D, Pires R, Gomes ER, Carter DE, Gomez MV, Guatimosim S, Prado VF, Prado MAM, Gros R. An analysis of the myocardial transcriptome in a mouse model of cardiac dysfunction with decreased cholinergic neurotransmission. PLoS One. 7(6):e39997 (2012).

14. Souza IA, Cino EA, Choy WY, Cordeiro MN, Richardon M, Chavez-Olortegui C, Gomez MV, Prado MAM, Prado VF. Expression of a recombinant Phoneutria toxin active in calcium channels. Toxicon 60(5):907-918 (2012).

15. Rocha-Resende C, Roy A, Resende R, Ladeira MS, Lara A, de Morais Gomes ER, Prado VF, Gros R, Guatimosim C, Prado MAM, Guatimosim S. Non-neuronal cholinergic machinery present in cardiomyocytes offsets hypertrophic signals. J Mol Cell Cardiol. 53(2):206-216 (2012).

16. 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.  Elimination of the vesicular acetylcholine transporter in the striatum reveals regulation of behaviour by cholinergic-glutamatergic co-transmission. PLoS Biol 9(11): e1001194 (2011).

17. Martins-Silva C, De Jaeger X, Guzman MS, Lima RD, Santos MS, Kushmerick C, Gomez MV, Caron MG, Prado MAM, Prado VF. Novel strains of mice deficient for the vesicular acetylcholine transporter: Insights on transcriptional regulation and control of locomotor behaviour.  PLoS One 6(3):e17611 (2011).

18. de Castro BM, De Jaeger X, Martins-Silva C, Lima RD, Amaral E, Menezes C, Lima P, Neves CM, Pires RG, Gould TG, Welch I, Kushmerick C, Guatimosim C, Izquierdo I, Cammarota M, Rylett RJ, Gomez MV, Caron MG, Oppenheim RW, Prado MAM, Prado VF. The vesicular acetylcholine transporter is required for neuromuscular development and function. Mol Cell Biol. 29:5238-5250 (2009).

19. 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).

20. Caetano FA, Lopes MH, Haijj GN, Machado CF, Arantes C, Magalhães AC,  Vieira Mde P, Américo TA, Massensini AR, Priola SA, Vorberg I, Gomez MV, Linden R, Prado VF, Martins VR, Prado MAM. Endocytosis of prion protein is required for ERK1/2 signaling induced by stress-inducible protein 1. J Neurosci. 28: 6691-6702 (2008).

21. 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. Mice deficient for the vesicular acetylcholine transporter are myasthenic and have deficits in object and social recognition. Neuron.  51(5):601-612 (2006).

Contact Information

Robarts Research Institute                                                                  
The University of Western Ontario                                                    
1151 Richmond St. N.                                                            
London, ON N6A 5B7                                                                               
Tel:  519-931-5777 Ext. 24889                                                              
Fax: 519-931-5789