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iPSC-derived astrocytes from patients with depression to investigate the influence of omega-3 fatty acids

2020
University of Illinois at Chicago, Chicago, USA
Clinical and laboratory studies suggest that omega-3 fatty acids could help with severe depression. However, the mechanisms underlying these potentially therapeutic properties are still unknown. There is evidence that certain brain cells, the glial cells, do not function properly in depression and that antidepressants can improve this function. In this study, neural stem cell lines derived from induced pluripotent stem cells from patients with depression were produced in the laboratory and used to grow astrocytes that were detected with the protein GFAP. These cells were then treated with various fatty acids: Eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) - both omega-3 fatty acids - and stearic acid (SA). It was observed that EPA and DHA led to more GFAP being formed and more astrocytes being present. In addition, the astrocytes of the patients produced more of two important growth factors for nerve cells, BDNF and GDNF, after treatment with omega-3 fatty acids. Stearic acid did not have this effect. The activity of a certain protein called CREB was also increased by DHA and EPA, but not by stearic acid. When the astrocytes were treated with omega-3 fatty acids and a substance that normally affects CREB (RP-cAMPs) was used at the same time, it did not block CREB activation by the omega-3 fatty acids. However, another substance that specifically inhibits CREB (666-15) reduced the production of BDNF and GDNF induced by omega-3 fatty acids. This suggests that the effect of omega-3 fatty acids is dependent on CREB. These results suggest that omega-3 fatty acids may act in a similar way to some antidepressants by increasing these important nerve growth factors. This could mean that omega-3 fatty acids could play a supportive role in the treatment of depression. This research also highlights the importance of astrocytes in depression and its treatment.
N-3 polyunsaturated fatty acids promote astrocyte differentiation and neurotrophin production independent of cAMP in patient-derived neural stem cells
Mark M. Rasenick, Jiang-Zhou Yu
#2171
Added on: 04-28-2025
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