| Title | Loss of PINK1 causes age-dependent decrease of dopamine release and mitochondrial dysfunction |
| Authors | Zhi, Lianteng Qin, Qi Muqeem, Tanziyah Seifert, Erin L. Liu, Wencheng Zheng, Sushuang Li, Chenjian Zhang, Hui |
| Affiliation | Thomas Jefferson Univ, Dept Neurosci, Philadelphia, PA 19107 USA Thomas Jefferson Univ, Dept Pathol, Philadelphia, PA 19107 USA Cornell Univ, Weill Med Coll, Dept Neurol & Neurosci, New York, NY 10021 USA Peking Univ, Sch Life Sci, Beijing, Peoples R China |
| Keywords | PINK1 Dopamine release Parkinson's disease Mitochondria dysfunction Mitochondria respiration Fast-scan cyclic voltammetry |
| Issue Date | 2019 |
| Publisher | NEUROBIOLOGY OF AGING |
| Abstract | Mutations and deletions in PTEN-induced kinase 1 (PINK1) cause autosomal recessive Parkinson's disease (PD), the second most common neurodegenerative disorder. PINK1 is a nuclear-genome encoded Ser/Thr kinase in mitochondria. PINK1 deletion was reported to affect dopamine (DA) levels in the striatum and mitochondrial functions but with conflicting results. The role of PINK1 in mitochondrial function and in PD pathogenesis remains to be elucidated thoroughly. In this study, we measured DA release using fast-scan cyclic voltammetry in acute striatal slices from both PINK1 knockout (KO) and wild-type (WT) mice at different ages. We found that single pulse-evoked DA release in the dorsal striatum of PINK1 KO mice was decreased in an age-dependent manner. Furthermore, the decrease was because of less DA release instead of an alteration of DA transporter function or DA terminal degeneration. We also found that PINK1 KO striatal slices had significantly lower basal mitochondria respiration compared with that of WT controls, and this impairment was also age-dependent. These results suggest that the impaired DA release is most likely because of mitochondrial dysfunction and lower ATP production. (C) 2018 Elsevier Inc. All rights reserved. |
| URI | http://hdl.handle.net/20.500.11897/550482 |
| ISSN | 0197-4580 |
| DOI | 10.1016/j.neurobiolaging.2018.10.025 |
| Indexed | SCI(E) EI |
| Appears in Collections: | 生命科学学院 |
