Progressive Axonal Degeneration of Nigrostriatal Dopaminergic Neurons in Calcium-Independent Phospholipase A2β Knockout Mice.
Calcium-independent phospholipase A2β (iPLA2β, 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...
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doaj-29a236bcf0bf4055b3a5965fbbcdc51c2020-11-25T00:48:33ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01114e015378910.1371/journal.pone.0153789Progressive Axonal Degeneration of Nigrostriatal Dopaminergic Neurons in Calcium-Independent Phospholipase A2β Knockout Mice.Goichi BeckKoei ShinzawaHideki HayakawaKousuke BabaHisae Sumi-AkamaruYoshihide TsujimotoHideki MochizukiCalcium-independent phospholipase A2β (iPLA2β, 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 iPLA2β-knockout (KO) mice. To clarify whether a deficiency of iPLA2β leads to the degeneration of nigrostriatal dopaminergic neurons, we analyzed the striatum of iPLA2β-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 iPLA2β-KO mice, focal loss of nerve terminals positive for TH and DAT was found from 56 weeks (early clinical stage), although iPLA2β-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 iPLA2β-KO mice. Moreover, strongly TH-positive structures, presumed to be deformed axons, were observed in the neuropils of the striatum of iPLA2β-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 iPLA2β-KO mice.http://europepmc.org/articles/PMC4831782?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Goichi Beck Koei Shinzawa Hideki Hayakawa Kousuke Baba Hisae Sumi-Akamaru Yoshihide Tsujimoto Hideki Mochizuki |
spellingShingle |
Goichi Beck Koei Shinzawa Hideki Hayakawa Kousuke Baba Hisae Sumi-Akamaru Yoshihide Tsujimoto Hideki Mochizuki Progressive Axonal Degeneration of Nigrostriatal Dopaminergic Neurons in Calcium-Independent Phospholipase A2β Knockout Mice. PLoS ONE |
author_facet |
Goichi Beck Koei Shinzawa Hideki Hayakawa Kousuke Baba Hisae Sumi-Akamaru Yoshihide Tsujimoto Hideki Mochizuki |
author_sort |
Goichi Beck |
title |
Progressive Axonal Degeneration of Nigrostriatal Dopaminergic Neurons in Calcium-Independent Phospholipase A2β Knockout Mice. |
title_short |
Progressive Axonal Degeneration of Nigrostriatal Dopaminergic Neurons in Calcium-Independent Phospholipase A2β Knockout Mice. |
title_full |
Progressive Axonal Degeneration of Nigrostriatal Dopaminergic Neurons in Calcium-Independent Phospholipase A2β Knockout Mice. |
title_fullStr |
Progressive Axonal Degeneration of Nigrostriatal Dopaminergic Neurons in Calcium-Independent Phospholipase A2β Knockout Mice. |
title_full_unstemmed |
Progressive Axonal Degeneration of Nigrostriatal Dopaminergic Neurons in Calcium-Independent Phospholipase A2β Knockout Mice. |
title_sort |
progressive axonal degeneration of nigrostriatal dopaminergic neurons in calcium-independent phospholipase a2β knockout mice. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2016-01-01 |
description |
Calcium-independent phospholipase A2β (iPLA2β, 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 iPLA2β-knockout (KO) mice. To clarify whether a deficiency of iPLA2β leads to the degeneration of nigrostriatal dopaminergic neurons, we analyzed the striatum of iPLA2β-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 iPLA2β-KO mice, focal loss of nerve terminals positive for TH and DAT was found from 56 weeks (early clinical stage), although iPLA2β-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 iPLA2β-KO mice. Moreover, strongly TH-positive structures, presumed to be deformed axons, were observed in the neuropils of the striatum of iPLA2β-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 iPLA2β-KO mice. |
url |
http://europepmc.org/articles/PMC4831782?pdf=render |
work_keys_str_mv |
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