title: Behavioral phenotyping of Parkin-deficient mice: looking for early preclinical features of Parkinson's disease.
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.
authors.affiliation: Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, UFSC, Florianópolis, 88049-900, SC, Brazil; CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517, Coimbra, Portugal.
authors.forename: Daniel
authors.initials: D
authors.lastname: Rial
authors.affiliation: Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, UFSC, Florianópolis, 88049-900, SC, Brazil.
authors.forename: Adalberto A
authors.initials: AA
authors.lastname: Castro
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517, Coimbra, Portugal.
authors.forename: Nuno
authors.initials: N
authors.lastname: Machado
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517, Coimbra, Portugal.
authors.forename: Pedro
authors.initials: P
authors.lastname: Garção
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517, Coimbra, Portugal.
authors.forename: Francisco Q
authors.initials: FQ
authors.lastname: Gonçalves
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517, Coimbra, Portugal.
authors.forename: Henrique B
authors.initials: HB
authors.lastname: Silva
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517, Coimbra, Portugal; Department of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, 3000-456, Coimbra, Portugal.
authors.forename: Angelo R
authors.initials: AR
authors.lastname: Tomé
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517, Coimbra, Portugal.
authors.forename: Attila
authors.initials: A
authors.lastname: Köfalvi
authors.affiliation: CNRS UMR 7225, Hôpital de la Salpêtrière-Bâtiment, ICM (Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière), CRICM, Thérapeutique Expérimentale de la Neurodégénérescence, Université Pierre et Marie Curie, UPMC, 75651, Paris, France.
authors.forename: Olga
authors.initials: O
authors.lastname: Corti
authors.affiliation: CNRS UMR 7225, Hôpital de la Salpêtrière-Bâtiment, ICM (Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière), CRICM, Thérapeutique Expérimentale de la Neurodégénérescence, Université Pierre et Marie Curie, UPMC, 75651, Paris, France.
authors.forename: Rita
authors.initials: R
authors.lastname: Raisman-Vozari
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517, Coimbra, Portugal; Faculty of Medicine, University of Coimbra, 3005-504, Coimbra, Portugal.
authors.forename: Rodrigo A
authors.initials: RA
authors.lastname: Cunha
authors.affiliation: Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, UFSC, Florianópolis, 88049-900, SC, Brazil.
authors.forename: Rui D
authors.initials: RD
authors.lastname: Prediger
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D017353:Gene Deletion; D006624:Hippocampus / Q000378:metabolism / Q000503:physiopathology; D006720:Homozygote; D008124:Locomotion; D017774:Long-Term Potentiation; D008297:Male; D008568:Memory; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity; D009411:Nerve Endings / Q000378:metabolism; D010300:Parkinson Disease / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D010641:Phenotype; D044767:Ubiquitin-Protein Ligases / Q000172:deficiency* / Q000235:genetics*
chemical_list: D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D004298:Dopamine