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Characterization of Motor and Non-Motor Behavioral Alterations in the Dj-1 (PARK7) Knockout Rat

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Abstract

Parkinson’s disease is a neurodegenerative disorder that encompasses a constellation of motor and non-motor symptoms. The etiology of the disease is still poorly understood because of complex interactions between environmental and genetic risk factors. Using animal models to assess these risk factors may lead to a better understanding of disease manifestation. In this study, we assessed the Dj-1 knockout (KO) genetic rat model in a battery of motor and non-motor behaviors. We tested the Dj-1 KO rat, as well as age-matched wild-type (WT) control rats, in several sensorimotor tests at 2, 4, 7, and 13 months of age. The Dj-1-deficient rats were found to rear and groom less, and to have a shorter stride length than their WT counterparts, but to take more forelimb and hindlimb steps. In non-motor behavioral tasks, performed at several different ages, we evaluated the following: olfactory function, anxiety-like behavior, short-term memory, anhedonia, and stress coping behavior. Non-motor testing was conducted as early as 4.5 months and as late as 17 months of age. We found that Dj-1 KO animals displayed deficits in short-term spatial memory as early as 4.5 months of age during place preference testing, as well as impaired coping strategies in the forced swim test, which are consistent with a parkinsonian-like phenotype. In some instances, effects of chronic stress were evaluated in the Dj-1-deficient rats, as an initial test of an environmental challenge combined with a genetic disposition for PD. Although some of the results were mixed with differential effects across several of the behaviors, the combination of the changes we observed indicates that the Dj-1 KO rat may be a promising model for the assessment of the prodromal stage of Parkinson’s disease, but further evaluation is necessary.

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Acknowledgments

We are grateful to Dr. Sheila Fleming for expert training in several of the behavioral tasks. This work was supported by the Kerman Family Fund, the Selma Schottenstein Harris Lab for Research in Parkinson’s, the Gardner Family Center for Parkinson’s Disease and Movement Disorders, and the Parkinson’s Disease Support Network - Ohio, Kentucky and Indiana. AMH was supported by National Institutes of Health grant T32 DK059803.

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Authors and Affiliations

  1. Department of Neurology, University of Cincinnati College of Medicine, Cincinnati, OH, 45267, USA

    Tara L. Kyser, Ann M. Hemmerle & Kim B. Seroogy

  2. Neuroscience Graduate Program, University of Cincinnati, Cincinnati, OH, 45267, USA

    Tara L. Kyser, Adam J. Dourson, Michael T. Williams & Kim B. Seroogy

  3. Department of Anesthesia, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, 45229, USA

    Adam J. Dourson

  4. Department of Neurosurgery, University of Cincinnati College of Medicine, Cincinnati, OH, 45267, USA

    Jennifer L. McGuire

  5. Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, 45229, USA

    Michael T. Williams

  6. Division of Neurology, Cincinnati Children’s Research Foundation, Cincinnati, OH, 45229, USA

    Michael T. Williams

  7. The Selma Schottenstein Harris Laboratory for Research in Parkinson’s, Gardner Family Center for Parkinson’s Disease and Movement Disorders, Department of Neurology, University of Cincinnati College of Medicine, Medical Sciences Building, ML0536, 231 Albert Sabin Way, Cincinnati, OH, 45267-0536, USA

    Kim B. Seroogy

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  1. Tara L. Kyser
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Correspondence to Kim B. Seroogy.

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Kyser, T.L., Dourson, A.J., McGuire, J.L. et al. Characterization of Motor and Non-Motor Behavioral Alterations in the Dj-1 (PARK7) Knockout Rat. J Mol Neurosci 69, 298–311 (2019). https://doi.org/10.1007/s12031-019-01358-0

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