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Characterization of early-onset motor deficits in the Pink1-/- mouse model of Parkinson disease.

TitleCharacterization of early-onset motor deficits in the Pink1-/- mouse model of Parkinson disease.
Publication TypeJournal Article
Year of Publication2018
AuthorsKelm-Nelson CA, Brauer AFL, Barth KJ, Lake JM, Sinnen MLK, Stehula FJ, Muslu C, Marongiu R, Kaplitt MG, Ciucci MR
JournalBrain Res
Volume1680
Pagination1-12
Date Published2018 02 01
ISSN1872-6240
KeywordsAge Factors, Animals, Brain, Disease Models, Animal, Hindlimb, Locomotion, Mice, Mice, Inbred C57BL, Mice, Transgenic, Motor Activity, Parkinson Disease, Protein Kinases, Psychomotor Disorders, Tyrosine 3-Monooxygenase, Vocalization, Animal
Abstract

In Parkinson disease (PD), a complex neurodegenerative disorder that affects nearly 10 million people worldwide, motor skills are significantly impaired. However, onset and progression of motor deficits and the neural correlates of these deficits are poorly understood. We used a genetic mouse model of PD (Pink1-/-), with phenotypic similarities to human PD, to investigate the manifestation of early-onset sensorimotor deficits. We hypothesized this mouse model would show early vocalization and gross motor dysfunction that would be progressive in nature. Pink1-/- mice, compared to wild type (WT) controls, were evaluated at 2, 3, 4, 5, and 6 months of age. To quantify deficit progression, ultrasonic vocalizations and spontaneous locomotor activity (cylinder test and pole test) were analyzed. Although somewhat variable, in general, Pink1-/- mice produced significantly more simple calls with reduced intensity as well as a larger percentage of cycle calls compared to WT counterparts. However, there were no significant differences in duration, bandwidth, or peak frequency for any of the ultrasonic call types between genotypes. Pink1-/- mice showed a significant impairment in limb motor skills with fewer hindlimb steps, forelimb steps, and rears and lands in the cylinder test compared to WT. Additionally, Pink1-/- mice took significantly longer to turn and traverse during the pole test. Immunohistochemical staining showed no significant difference in the number of tyrosine hydroxylase (TH) positive cells in the substantia nigra or density of TH staining in the striatum between genotypes. These data suggest the Pink1-/- mouse model may be instrumental in defining early motor biomarkers of PD in the absence of nigrostriatal dopamine loss.

DOI10.1016/j.brainres.2017.12.002
Alternate JournalBrain Res
PubMed ID29229503
PubMed Central IDPMC5767140
Grant ListF32 DC014399 / DC / NIDCD NIH HHS / United States
R01 DC014358 / DC / NIDCD NIH HHS / United States