Ebert, Stefanie and Weigelt, Karin and Walczak, Yana and Drobnik, Wolfgang and Mauerer, Richard and Hume, David A. and Weber, Bernhard H. F. and Langmann, Thomas (2009) Docosahexaenoic acid attenuates microglial activation and delays early retinal degeneration. JOURNAL OF NEUROCHEMISTRY, 110 (6). pp. 1863-1875. ISSN 0022-3042, 1471-4159
Full text not available from this repository. (Request a copy)Abstract
Microgliosis is a common phenomenon in neurodegenerative disorders including retinal dystrophies. We performed a detailed characterization of activated microglia in the retinoschisin (Rs1h)-deficient (Rs1h(-/Y)) mouse model of inherited retinal degeneration. To visualize and isolate microglia, we crossed Rs1h(-/Y) animals with transgenic MacGreen mice, which express green fluorescent protein under the control of the macrophage-specific csf1r promoter. Activated microglia were detected in retinal sections and whole-mounts of early postnatal MacGreen/Rs1h(-/Y) mice before the onset of overt neuronal cell death. These activated microglia contained prominent lipid droplets and analysis of the retinal lipid composition showed decreased docosahexaenoic acid (DHA) levels in Rs1h(-/Y) retinas. To establish a link between microglia activation, reduced DHA levels, and neurodegeneration, a dietary intervention study was performed. Female Rs1h(-/-) mice and their Rs1h(-/Y) litter were either subjected to a diet enriched with DHA, or a control chow lacking DHA. Supplementation with DHA enhanced photoreceptor survival and converted activated microglia to a quiescent phenotype. Furthermore, DHA, but not docosapentaenoic acid or adrenic acid reduced pro-inflammatory gene expression, migration, and lipid accumulation of cultured BV-2 microglia. We conclude that retinal DHA levels control the activity of microglia and thereby may affect the progression and extent of retinal degeneration.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | N-3 FATTY-ACID; RETINOSCHISIN-DEFICIENT RETINA; LEBERS CONGENITAL AMAUROSIS; MEDIATED GENE-TRANSFER; IN-VIVO; CHILDHOOD BLINDNESS; NEUROPROTECTIN D1; CELL-SURVIVAL; CANINE MODEL; MOUSE RETINA; docosahexaenoic acid; microglia; retina; retinoschisis |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Humangenetik |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 09 Sep 2020 05:12 |
| Last Modified: | 09 Sep 2020 05:12 |
| URI: | https://pred.uni-regensburg.de/id/eprint/28503 |
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