Department of Cell Biology and Imaging, Institute of Zoology and Biomedical Research, Jagiellonian University, Kraków, Poland.
Eur J Neurosci. 2021 Sep;54(5):5785-5797. doi: 10.1111/ejn.15171. Epub 2021 Mar 17.
DmMANF, Drosophila melanogaster mesencephalic astrocyte-derived neurotrophic factor (DmMANF) is an evolutionarily conserved orthologue of mammalian MANF. This neurotrophic factor exerts many functions in the Drosophila brain, particularly those dependent on glial cells. As we found in our earlier study, downregulation of DmMANF in glia induces degeneration of glial cells in the first optic neuropil (lamina) where DmMANF abundance is especially high. In the present study, we observed that changes in the level of DmMANF in two types of glia, astrocyte-like glia (AlGl) and ensheathing glia (EnGl), affect activity and sleep of flies. Interestingly, a proper level of DmMANF in AlGl seems to be important in guiding processes of pigment dispersing factor (PDF)-expressing clock neurons. This is supported by our finding that DmMANF overexpression in AlGl leads to structural changes in the architecture of the PDF-positive arborization in the brain. Finally, we detected that DmMANF also affects rhythms in glia themselves, as circadian oscillations in expression of the catalytic α subunit of the sodium pump in the lamina epithelial glia were abolished after DmMANF silencing. DmMANF expressed in AlGl and EnGl seems to affect the activity of neurons leading to changes in behaviour.
DmMANF，即黑腹果蝇中脑星形胶质细胞衍生的神经营养因子（DmMANF），是哺乳动物 MANF 的进化保守同源物。这种神经营养因子在果蝇大脑中发挥着许多功能，特别是那些依赖于神经胶质细胞的功能。正如我们在早期研究中发现的，神经胶质细胞中 DmMANF 的下调会诱导第一视神经（神经纤维层）中神经胶质细胞的退化，而 DmMANF 在该处的丰度特别高。在本研究中，我们观察到两种神经胶质细胞——星形胶质细胞样神经胶质细胞（AlGl）和鞘状神经胶质细胞（EnGl）中 DmMANF 水平的变化会影响果蝇的活动和睡眠。有趣的是，AlGl 中适当水平的 DmMANF 似乎对指导表达色素分散因子（PDF）的时钟神经元的过程很重要。这一观点得到了我们的发现的支持，即 DmMANF 在 AlGl 中的过表达会导致大脑中 PDF 阳性树突分支结构的变化。最后，我们还发现 DmMANF 也会影响神经胶质细胞自身的节律，因为在 DmMANF 沉默后，神经纤维层上皮神经胶质细胞中钠泵催化α亚基的表达的昼夜节律性振荡被消除。在 AlGl 和 EnGl 中表达的 DmMANF 似乎会影响神经元的活动，从而导致行为的变化。
