Event Abstract Back to Event Intraneuronal delivery of exogenous tau protein mediated by halitoxins may serve as a pharmacological animal model of human tauopathy in rats Grazyna Niewiadomska1*, Anna Mietelska-Porowska1, Davide Koss2, Ita Robakiewicz1 and Bettina Platt2 1 Nencki Institute, Department of Neurophysiology, Poland 2 University of Aberdeen, Institute of Medical Science, United Kingdom “Tauopathies” comprise a number of dementias characterised by the abnormal aggregation of the protein “tau” in brain. Alzheimer’s disease is probably the best known and is characterised by a progressive cognitive decline in old age. Why aggregation of tau kills neurones is unknown and good animal models that mimic the AD condition remain still elusive. We propose establishment of such a model through the direct infusion of tau into the brain to increase levels of tau so much so that it may render the nerve cells malfunctioning. The use of aged rats (15 months old) is predicted to aid the establishment of this model since neurons may be more vulnerable to high tau and behavioural consequences may become more readily accessible. This model was developed using pore-forming halitoxin Poly-APS and Tau was delivered through the membrane pores into the hippocampal neurons. Rats were injected with recombinant human Tau441 only (controls), Tau+Poly-APS (double) and Tau+Poly-APS+Okadaic Acid (triple). It was expected that tau administration will lead to changes in affected neurones and this will result in learning and memory deficits. The mechanism of action has been investigated in brain tissue harvested from the animals. Cognitive and neurodegenerative changes were examined with Morrris water maze behavioral test and immunohistochemistry, respectively. Acquisition of the spatial reference memory was unaffected by administration of Tau or Tau+Poly-APS. However, enhanced phosphorylation of tau delivered with the triple infusion impaired learning. Once inside the cell, exogenous tau subjected to phosphorylation by intracellular kinases and this led to tau aggregation and breakdown of the cytoskeleton. This enables a development of successful model in which anti-dementia drugs could be tested in order to revert tau-dependent neurodegeneration and cognitive decline. The model may also prove valuable to develop new treatment regimes for the benefit of dementia patients. Conference: 41st European Brain and Behaviour Society Meeting, Rhodes Island, Greece, 13 Sep - 18 Sep, 2009. Presentation Type: Poster Presentation Topic: Poster presentations Citation: Niewiadomska G, Mietelska-Porowska A, Koss D, Robakiewicz I and Platt B (2009). Intraneuronal delivery of exogenous tau protein mediated by halitoxins may serve as a pharmacological animal model of human tauopathy in rats. Conference Abstract: 41st European Brain and Behaviour Society Meeting. doi: 10.3389/conf.neuro.08.2009.09.246 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 12 Jun 2009; Published Online: 12 Jun 2009. * Correspondence: Grazyna Niewiadomska, Nencki Institute, Department of Neurophysiology, Granz, Poland, g.niewiadomska@nencki.edu.pl Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Grazyna Niewiadomska Anna Mietelska-Porowska Davide Koss Ita Robakiewicz Bettina Platt Google Grazyna Niewiadomska Anna Mietelska-Porowska Davide Koss Ita Robakiewicz Bettina Platt Google Scholar Grazyna Niewiadomska Anna Mietelska-Porowska Davide Koss Ita Robakiewicz Bettina Platt PubMed Grazyna Niewiadomska Anna Mietelska-Porowska Davide Koss Ita Robakiewicz Bettina Platt Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.