Characterization of early-onset motor deficits in the Pink1-/- mouse model of Parkinson disease
| Autor: | Michelle R. Ciucci, Cagla Muslu, Kelsey J. Barth, Michael G. Kaplitt, Alexander F.L. Brauer, Jacob M. Lake, Roberta Marongiu, Forrest J. Stehula, Cynthia A. Kelm-Nelson, Mackenzie L.K. Sinnen |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Tyrosine 3-Monooxygenase Gross motor skill Substantia nigra Mice Transgenic Hindlimb Striatum Biology Motor Activity Article 03 medical and health sciences Mice 0302 clinical medicine Internal medicine medicine Animals Molecular Biology Motor skill Tyrosine hydroxylase General Neuroscience Wild type Age Factors Brain Parkinson Disease Mice Inbred C57BL Disease Models Animal 030104 developmental biology Endocrinology medicine.anatomical_structure Neurology (clinical) Forelimb Psychomotor Disorders Vocalization Animal Protein Kinases 030217 neurology & neurosurgery Locomotion Developmental Biology |
| Zdroj: | Brain research. 1680 |
| ISSN: | 1872-6240 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect