Mario Plaas "Animal model of Wolfram Syndrome in mice: behavioural, biochemical and psychopharmacological characterization" | University of Tartu

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Contacts of UT units

Faculty of Arts and Humanities
Faculty phone: 
+372 737 5341
Faculty address: 
Jakobi 2, rooms 116–121, 51005 Tartu
  • Dean's Office
    Faculty phone: 
    + 372 737 5341
    Faculty address: 
    Jakobi 2, rooms 116–121, 51005 Tartu
  • Institute of History and Archaeology
    Faculty phone: 
    +372 737 5651
    Faculty address: 
    Jakobi 2, 51005 Tartu
  • Institute of Estonian and General Linguistics
    Faculty phone: 
    +372 737 5221
    Faculty address: 
    Jakobi 2, 51005 Tartu
  • Institute of Philosophy and Semiotics
    Faculty phone: 
    +372 737 5314
    Faculty address: 
    Jakobi 2, rooms 309–352, 51005 Tartu
  • Institute of Cultural Research
    Faculty phone: 
    (+372) 737 5223
    Faculty address: 
    Ülikooli 16, 51003 Tartu
  • School of Theology and Religious Studies
    Faculty phone: 
    +372 737 5301
    Faculty address: 
    Ülikooli 18–310, 50090 Tartu
  • College of Foreign Languages and Cultures
    Faculty address: 
    J. Liivi 4, 50409, Tartu
  • Viljandi Culture Academy
    Faculty phone: 
    +372 435 5232
    Faculty address: 
    Posti 1, 71004 Viljandi
Faculty of Social Sciences
Faculty phone: 
+372 737 5957
Faculty address: 
Lossi 36, 51003 Tartu
  • Dean's Office
    Faculty phone: 
    + 372 737 5900
    Faculty address: 
    Lossi 36, 51003 Tartu
  • Institute of Education
    Faculty phone: 
    +372 737 6440
    Faculty address: 
    Salme 1a–29, 50103 Tartu
  • Johan Skytte Institute of Political Studies
    Faculty phone: 
    +372 737 5582
    Faculty address: 
    Lossi 36–301, 51003 Tartu
  • School of Economics and Business Administration
    Faculty phone: 
    +372 737 6310
    Faculty address: 
    Narva mnt 18, 51009 Tartu
  • Institute of Psychology
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    Faculty address: 
    Näituse 2, 50409 Tartu
  • School of Law
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    Näituse 20–324, 50409 Tartu
  • Institute of Social Studies
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    Lossi 36, 51003 Tartu
  • Narva College
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  • Pärnu College
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    Ringi 35, 80012 Pärnu
Faculty of Medicine
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Ravila 19, 50411 Tartu
  • Dean's Office
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    +372 737 5326
    Faculty address: 
    Ravila 19, 50411 Tartu
  • Institute of Biomedicine and Translational Medicine
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    +372 737 4210
    Faculty address: 
    Biomeedikum, Ravila 19, 50411 Tartu
  • Institute of Pharmacy
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    Nooruse 1, 50411 Tartu
  • Institute of Dentistry
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    Faculty address: 
    Raekoja plats 6, 51003 Tartu
  • Institute of Clinical Medicine
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    Faculty address: 
    L. Puusepa 8, 50406 Tartu
  • Institute of Family Medicine and Public Health
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    Faculty address: 
    Ravila 19, 50411 Tartu
  • Institute of Sport Sciences and Physiotherapy
    Faculty phone: 
    +372 737 5360
    Faculty address: 
    Jakobi 5–205, 51005 Tartu
Faculty of Science and Technology
Faculty phone: 
+372 737 5820
Faculty address: 
Vanemuise 46–208, 51014 Tartu
  • Dean's Office
    Faculty phone: 
    +372 737 5820
    Faculty address: 
    Vanemuise 46–208, 51003 Tartu
  • Institute of Computer Science
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    Faculty address: 
    Narva mnt 18, 51009 Tartu
  • Estonian Marine Institute
    Faculty phone: 
    +372 671 8902
    Faculty address: 
    Mäealuse 14, 12618 Tallinn
  • Institute of Physics
    Faculty address: 
    W. Ostwaldi 1, 50411 Tartu
  • Institute of Chemistry
    Faculty phone: 
    +372 737 5261
    Faculty address: 
    Ravila 14a, 50411 Tartu
  • Institute of Mathematics and Statistics
    Faculty phone: 
    +372 737 5860
    Faculty address: 
    Narva mnt 18, 51009 Tartu
  • Institute of Molecular and Cell Biology
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    +372 737 5027
    Faculty address: 
    Riia 23, 23b–134, 51010 Tartu
  • Tartu Observatory
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    +372 737 4510
    Faculty address: 
    Observatooriumi 1, Tõravere, 61602 Tartumaa
  • Institute of Technology
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    Faculty address: 
    Nooruse 1, 50411 Tartu
  • Institute of Ecology and Earth Sciences
    Faculty phone: 
    +372 737 5835
    Faculty address: 
    Vanemuise 46, 51003 Tartu
Institutions
  • Library
    Faculty phone: 
    +372 737 5702
    Faculty address: 
    W. Struve 1, 50091 Tartu
  • Youth Academy
    Faculty phone: 
    +372 737 5581
    Faculty address: 
    Uppsala 10, 51003 Tartu
  • Institute of Genomics
    Faculty phone: 
    +372 737 4000
    Faculty address: 
    Riia 23b, 51010 Tartu
  • Museum
    Faculty phone: 
    +372 737 5674
    Faculty address: 
    Lossi 25, 51003 Tartu
  • University of Tartu Natural History Museum and Botanical Garden
    Faculty phone: 
    +372 737 6076
    Faculty address: 
    Vanemuise 46, 51003 Tartu
Support Units
  • Administrative Office
    Faculty phone: 
    +372 737 5606
    Faculty address: 
    Ülikooli 18a, 51005 Tartu
  • Centre for Entrepreneurship and Innovation
    Faculty phone: 
    +372 737 4809
    Faculty address: 
    Narva mnt 18, 51009, Tartu
  • University Office in Tallinn
    Faculty phone: 
    +372 737 6600
    Faculty address: 
    Teatri väljak 3, 10143 Tallinn
  • Estates Office
    Faculty phone: 
    +372 737 5137
    Faculty address: 
    Ülikooli 18a, 51005 Tartu
  • Finance Office
    Faculty phone: 
    +372 737 5125
    Faculty address: 
    Jakobi 4, 51005 Tartu
  • Grant Office
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    +372 737 6215
    Faculty address: 
    Raekoja plats 9, 51004 Tartu
  • Information Technology Office
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    +372 737 6000, IT-help: +372 737 5500
    Faculty address: 
    Ülikooli 18a, 51005 Tartu
  • Human Resources Office
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    +372 737 5145
    Faculty address: 
    Ülikooli 18, rooms 302 and 304, 50090 Tartu
  • Internal Audit Office
    Faculty address: 
    Ülikooli 18-244, 51005 Tartu
  • Marketing and Communication Office
    Faculty phone: 
    +372 737 5687
    Faculty address: 
    Ülikooli 18, rooms 102, 104, 209, 210, 50090 Tartu
  • Office of Academic Affairs
    Faculty phone: 
    +372 737 5620
    Faculty address: 
    Ülikooli 18, 50090 Tartu
  • Procurement Office
    Faculty phone: 
    +372 737 6632
    Faculty address: 
    Ülikooli 18a, 51005 Tartu
  • Rector's Strategy Office
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    +372 737 5600
    Faculty address: 
    Ülikooli 18, 50090 Tartu
  • Student Council
    Faculty address: 
    Ülikooli 18b, 51005 Tartu
  • University of Tartu Press
    Faculty phone: 
    +372 737 5945
    Faculty address: 
    W. Struve 1, 50091 Tartu
Other Units
  • University of Tartu Academic Sports Club
    Faculty phone: 
    +372 737 5371
    Faculty address: 
    Ujula 4, 51008 Tartu
  • Tartu Student Village
    Faculty phone: 
    +372 740 9959
    Faculty address: 
    Narva mnt 25, 51013 Tartu
  • Tartu Students’ Club
    Faculty phone: 
    +372 730 2400
    Faculty address: 
    Kalevi 24, 51010 Tartu
  • Tartu University Hospital
    Faculty address: 
    L. Puusepa 1a, 50406 Tartu
  • University of Tartu Foundation
    Faculty phone: 
    +372 737 5852
    Faculty address: 
    Ülikooli 18, 50090 Tartu
  • View all other units

Mario Plaas "Animal model of Wolfram Syndrome in mice: behavioural, biochemical and psychopharmacological characterization"

Date: 
24.10.2013 - 15:00 to 17:00

Mario Plaas will defence his doctoral thesis "Animal model of Wolfram Syndrome in mice: behavioural, biochemical and psychopharmacological characterization" on the 24 October at 3 pm in the Institute of Molecular and Cell Biology of the University of Tartu (Riia 23B - 105).

Supervisors:
Prof Eero Vasar, University of Tartu
Prof Alar Karis, University of Tartu
Prof Sulev Kõks, University of Tartu

Opponent:
Senior Lecturer Atso Raasmaja, Department of Pharmacy and Toxicology of the University of Helsinki

Summary:
Wolfram syndrome (WS), first described by German physicians Wolfram and Wagener in 1938, is a rare autosomal reces¬sive neurodegenerative disorder characterised by early juvenile diabetes mellitus, progressive optic nerve atrophy, diabetes insipidus and deafness. Wolfram syndrome is caused by mutations in the wolframin (WFS1) gene. In mice and rats, the wolframin gene has been associated with fear and anxiety; in humans, there is a link between WFS1 polymorphisms and increased risk for mood disorders, such as the psychotic form of bipolar disorder, schizophrenia, suicidal behaviour and depression. At present, it is not yet quite clear, how disruptions in the WFS1 gene cause neuropsychiatric deviations. However, based on the fact that WS is accompanied by psychiatric symptoms and also based on the localisation of the Wfs1 protein in the brain it can be concluded that at least partially it is caused by deviations in the functioning of the GABAergic and dopaminergic systems. The main objective of this dissertation was the creation of a WS mouse model. For that purpose, a mutant mouse line was created by deleting exon 8 in the Wfs1 gene as in WS patients most of the mutations are located in that exon. By this approach we managed to mimic WS in order to study pathological changes induced by the syndrome. To characterise the animals, behavioural, biochemical and psychopharmacological methods were used. Wfs1 mutant mice had no overt sensory deficits, however, they were more sensitive to stress-inducing environments (tests). Also, as compared to wild-type mice, they displayed a much more prominent increase in the level of corticosterone in the circulating blood in response to acute saline injection, and they were unable to keep their blood glucose level under control in the glucose tolerance test. Wfs1-deficient mice had increased sensitivity to the anxiolytic effect of GABA A recep¬tor agonist diazepam. Also, in Wfs1 mice diazepam blocked characteristic vocalisations in a stressful situation. Wfs1-deficient mice had lower expression level of Gabra1 and Gabra2 genes in the temporal and frontal lobes, brain structures involved in the regulation of negative emotions. These decreased expression levels are probably related to hypersensitivity to the anxiolytic effect of diazepam observed in Wfs1-deficient mice. In wild-type mice, a similar drop in the expression levels of Gabra1 and Gabra2 genes was evident after exposure to the plus maze (a model of anxiety), which indicates that there is a link between decreased expression levels of GABA A receptor subtypes and anxiety. Furthermore, mice lacking the wolframin protein had deviations in the function of the dopaminergic system. Their sensitivity to the motor stimulant effect of amphetamine, an indirect agonist of dopamine, had decreased and the administration of amphetamine failed to induce changes in dopamine turnover in the dorsal and ventral striatum as opposed to their wild-type littermates. Apomorphine-induced motor stimulation was somewhat stronger in mutant mice, but in all genotypes apomorphine caused a similar decrease in dopamine turnover. This enables us to conclude that Wfs1 gene deficiency has no effect on dopamine metabolism mediated by dopamine receptors. This is corroborated by the results of gene expression measurements showing that in the ventral striatum the expression level of dopamine D2 receptor (Drd2) was equal in all genotypes. However, both in male and female Wfs1-deficient mice the expression level of the dopamine transporter gene had decreased in the mesencephalon. This finding and also the decreased behavioural and biochemical effects of amphetamine are indicative of serious deviations in the function of the dopaminergic system in Wfs1-deficient mice. Based on the results of glucose metabolism studies and their similarity to WS, it is clear that the mouse, missing exon 8 of the Wfs1 gene, is a valid model of both WS syndrome and other disorders caused by mutations in the WFS1 gene. Therefore, the changes observed in the activity of the dopaminergic and GABAergic systems in Wfs1-deficient mice may also help to explain the neuropsychiatric symptoms of WS patients.

Organizer: 
Location: 
Riia 23B-105
Event category: