Behavioral phenotyping of Parkin-deficient mice: Looking for early preclinical features of Parkinson's disease

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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 nonmotor 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.

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Rial, D., Castro, A. A., Machado, N., Garҫão, P., Gonҫalves, F. Q., Silva, H. B., … Prediger, R. D. (2014). Behavioral phenotyping of Parkin-deficient mice: Looking for early preclinical features of Parkinson’s disease. PLoS ONE, 9(12). https://doi.org/10.1371/journal.pone.0114216

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