| First Author | Beck G | Year | 2016 |
| Journal | PLoS One | Volume | 11 |
| Issue | 4 | Pages | e0153789 |
| PubMed ID | 27078024 | Mgi Jnum | J:249141 |
| Mgi Id | MGI:6093212 | Doi | 10.1371/journal.pone.0153789 |
| Citation | Beck G, et al. (2016) Progressive Axonal Degeneration of Nigrostriatal Dopaminergic Neurons in Calcium-Independent Phospholipase A2beta Knockout Mice. PLoS One 11(4):e0153789 |
| abstractText | Calcium-independent phospholipase A2beta (iPLA2beta, PLA2G6) is essential for the remodeling of membrane glycerophospholipids. Mutations in this gene are responsible for autosomal recessive, young onset, L-dopa-responsive parkinsonism (PARK14), suggesting a neurodegenerative condition in the nigrostriatal dopaminergic system in patients with PLA2G6 mutations. We previously observed slowly progressive motor deficits in iPLA2beta-knockout (KO) mice. To clarify whether a deficiency of iPLA2beta leads to the degeneration of nigrostriatal dopaminergic neurons, we analyzed the striatum of iPLA2beta-KO mice. At all clinical stages, nerve terminals in the striatum were immunopositive for tyrosine hydroxylase (TH) and dopamine transporter (DAT) in wild-type (WT) control mice. In iPLA2beta-KO mice, focal loss of nerve terminals positive for TH and DAT was found from 56 weeks (early clinical stage), although iPLA2beta-KO mice at 56 weeks showed no significant decrease in the number of dopaminergic neurons in the substantia nigra compared with age-matched WT mice, as reported previously. At 100 weeks (late clinical stage), greater decreases in DAT immunoreactivity were observed in the striatum of iPLA2beta-KO mice. Moreover, strongly TH-positive structures, presumed to be deformed axons, were observed in the neuropils of the striatum of iPLA2beta-KO mice starting at 15 weeks (preclinical stage) and increased with age. These results suggest that the degeneration of dopaminergic neurons occurs mainly in the distal region of axons in iPLA2beta-KO mice. |
