Downregulation of DmMANF in Glial Cells Results in Neurodegeneration and Affects Sleep and Lifespan in Drosophila melanogaster
| Autor: | Ewelina Kijak, Elżbieta M. Chwastek, Wojciech Krzeptowski, Olga Woznicka, Elżbieta Pyza, Tapio I. Heino, Lucyna Walkowicz, Vassilis Stratoulias, Jolanta Górska-Andrzejak |
|---|---|
| Přispěvatelé: | Biosciences, Genetics |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Autophagosome Biology lcsh:RC321-571 03 medical and health sciences PARKINSONS-DISEASE Downregulation and upregulation CDNF Neurotrophic factors CDNF/MANF FAMILY Neuropil medicine neurotrophic factor lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Cerebral dopamine neurotrophic factor Original Research MANF PHOTORECEPTOR TERMINALS General Neuroscience Endoplasmic reticulum Neurodegeneration Dopaminergic VISUAL-SYSTEM 3112 Neurosciences neurodegeneration BRAIN DEGENERATION DOPAMINERGIC-NEURONS medicine.disease OPTIC NEUROPIL 030104 developmental biology medicine.anatomical_structure nervous system CDNF PROTECTS CAPITATE PROJECTIONS visual system neuroprotection Neuroscience |
| Zdroj: | Frontiers in Neuroscience Frontiers in Neuroscience, Vol 11 (2017) |
| ISSN: | 1662-453X 1662-4548 |
| Popis: | In Drosophila melanogaster, mesencephalic astrocyte-derived neurotrophic factor(DmMANF) is an evolutionarily conserved ortholog of mammalian MANF and cerebral dopamine neurotrophic factor (CDNF), which have been shown to promote the survival of dopaminergic neurons in the brain. We observed especially high levels of DmMANF in the visual system of Drosophil a, particularly in the first optic neuropil (lamina). In the lamina, DmMANF was found in glial cells (surface and epithelial glia), photoreceptors and interneurons. Interestingly, silencing of DmMANF in all neurons or specifically in photoreceptors or L2 interneurons had no impact on the structure of the visual system. However, downregulation of DmMANF in glial cells induced degeneration of the lamina. Remarkably, this degeneration in the form of holes and/or tightly packed membranes was observed only in the lamina epithelial glial cells. Those membranes seem to originate from the endoplasmic reticulum, which forms autophagosome membranes. Moreover, capitate projections, the epithelial glia invaginations into photoreceptor terminals that are involved in recycling of the photoreceptor neurotransmitter histamine, were less numerous after DmMANF silencing either in neurons or glial cells. The distribution of the alpha subunit of Na+/K+-ATPase protein in the lamina cell membranes was also changed. At the behavioral level, silencing of DmMANF either in neurons or glial cells affected the daily activity/sleep pattern, and flies showed less activity during the day but higher activity during the night than did controls. In the case of silencing in glia, the lifespan of flies was also shortened. The obtained results showed that DmMANF regulates many functions in the brain, particularly those dependent on glial cells. |
| Databáze: | OpenAIRE |
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