Please use this identifier to cite or link to this item: https://hdl.handle.net/10316/109641
Title: Behavioral phenotyping of Parkin-deficient mice: looking for early preclinical features of Parkinson's disease
Authors: Rial, Daniel 
Castro, Adalberto A.
Machado, Nuno J. 
Garção, Pedro 
Gonçalves, Francisco Q. 
Silva, Henrique B. 
Tomé, Ângelo R. 
Köfalvi, Attila 
Corti, Olga
Raisman-Vozari, Rita
Cunha, Rodrigo A. 
Prediger, Rui D.
Issue Date: 2014
Publisher: Public Library of Science
Project: This work was supported by grants from Conselho Nacional de Desenvolvimento Cientı´fico e Tecnolo´gico (CNPq), Coordenac¸a˜o de Aperfeic¸oamento de Pessoal de Nı´vel Superior (CAPES-COFECUB 681-10), Programa de Apoio aos Nu´cleos de Exceleˆncia (PRONEX - Project NENASC), Fundac¸a˜o de Apoio a` Pesquisa do Estado de Santa Catarina (FAPESC), QREN (CENTRO-07-ST24-FEDER-002006). DR and AAC received scholarships from CNPq. RDP is supported by a research fellowship from CNPq. RRV and RAC are supported by Visitant Research fellowships from CNPq (Cieˆncia sem Fronteiras) 
Serial title, monograph or event: PLoS ONE
Volume: 9
Issue: 12
Abstract: There is considerable evidence showing that the neurodegenerative processes that lead to sporadic Parkinson's disease (PD) begin many years before the appearance of the characteristic motor symptoms. Neuropsychiatric, sensorial and cognitive deficits are recognized as early non-motor manifestations of PD, and are not attenuated by the current anti-parkinsonian therapy. Although loss-of-function mutations in the parkin gene cause early-onset familial PD, Parkin-deficient mice do not display spontaneous degeneration of the nigrostriatal pathway or enhanced vulnerability to dopaminergic neurotoxins such as 6-OHDA and MPTP. Here, we employed adult homozygous C57BL/6 mice with parkin gene deletion on exon 3 (parkin-/-) to further investigate the relevance of Parkin in the regulation of non-motor features, namely olfactory, emotional, cognitive and hippocampal synaptic plasticity. Parkin-/- mice displayed normal performance on behavioral tests evaluating olfaction (olfactory discrimination), anxiety (elevated plus-maze), depressive-like behavior (forced swimming and tail suspension) and motor function (rotarod, grasping strength and pole). However, parkin-/- mice displayed a poor performance in the open field habituation, object location and modified Y-maze tasks suggestive of procedural and short-term spatial memory deficits. These behavioral impairments were accompanied by impaired hippocampal long-term potentiation (LTP). These findings indicate that the genetic deletion of parkin causes deficiencies in hippocampal synaptic plasticity, resulting in memory deficits with no major olfactory, emotional or motor impairments. Therefore, parkin-/- mice may represent a promising animal model to study the early stages of PD and for testing new therapeutic strategies to restore learning and memory and synaptic plasticity impairments in PD.
URI: https://hdl.handle.net/10316/109641
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0114216
Rights: openAccess
Appears in Collections:FMUC Medicina - Artigos em Revistas Internacionais
FCTUC Ciências da Vida - Artigos em Revistas Internacionais
I&D CNC - Artigos em Revistas Internacionais

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