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| Content Provider | Springer Nature Link |
|---|---|
| Author | Blanchard, Helene Taha, Ameer Y. Cheon, Yewon Kim, Hyung Wook Turk, John Rapoport, Stanley I. |
| Copyright Year | 2014 |
| Abstract | Calcium-independent phospholipase A$_{2}$ group VIa (iPLA$_{2}$β) preferentially releases docosahexaenoic acid (DHA) from the sn-2 position of phospholipids. Mutations of its gene, PLA2G6, are found in patients with several progressive motor disorders, including Parkinson disease. At 4 months, PLA2G6 knockout mice (iPLA$_{2}$β$^{−/−}$) show minimal neuropathology but altered brain DHA metabolism. By 1 year, they develop motor disturbances, cerebellar neuronal loss, and striatal α-synuclein accumulation. We hypothesized that older iPLA$_{2}$β$^{−/−}$ mice also would exhibit inflammatory and other neuropathological changes. Real-time polymerase chain reaction and Western blotting were performed on whole brain homogenate from 15 to 20-month old male iPLA$_{2}$β$^{−/−}$ or wild-type (WT) mice. These older iPLA$_{2}$β$^{−/−}$ mice compared with WT showed molecular evidence of microglial (CD-11b, iNOS) and astrocytic (glial fibrillary acidic protein) activation, disturbed expression of enzymes involved in arachidonic acid metabolism, loss of neuroprotective brain derived neurotrophic factor, and accumulation of cytokine TNF-α messenger ribonucleic acid, consistent with neuroinflammatory pathology. There was no evidence of synaptic loss, of reduced expression of dopamine active reuptake transporter, or of accumulation of the Parkinson disease markers Parkin or Pink1. iPLA$_{2}$γ expression was unchanged. iPLA$_{2}$β deficient mice show evidence of neuroinflammation and associated neuropathology with motor dysfunction in later life. These pathological biomarkers could be used to assess efficacy of dietary intervention, antioxidants or other therapies on disease progression in this mouse model of progressive human motor diseases associated with a PLA2G6 mutation. |
| Starting Page | 1522 |
| Ending Page | 1532 |
| Page Count | 11 |
| File Format | |
| ISSN | 03643190 |
| Journal | Neurochemical Research |
| Volume Number | 39 |
| Issue Number | 8 |
| e-ISSN | 15736903 |
| Language | English |
| Publisher | Springer US |
| Publisher Date | 2014-06-12 |
| Publisher Place | Boston |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Calcium-independent phospholipase A2 (iPLA$_{2}$β) knockout Brain Parkinson disease Arachidonic and docosahexaenoic acid Motor disturbances Neuropathology Neurosciences Neurochemistry Biochemistry Cell Biology Neurology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Medicine Biochemistry Cellular and Molecular Neuroscience |
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