2016 Fiscal Year Research-status Report
Beneficial role of plasmalogens in the brain which are reduced by ageing, stress and neuroinflammation
| Project/Area Number |
16K19007
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| Research Institution | Kyushu University |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Keywords | plasmalogens / hippocampus / neurotrophic factor / spatial learning / orphan GPR / NF-kB / c-Myc |
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| Outline of Annual Research Achievements |
In the first year, I could find out that the Plasmalogens (Pls) diet in the mice increased the hippocampal dependent memory. This memory improvement was associated with the increased expression of hippocampal BDNF expression and enhanced localization of TrkB receptors into the lipid rafts. I also found that the Pls diet reduces the amyloid beta (Aβ) protein deposition in the triple transgenic Alzheimer’s disease (AD) mice model. These results have been summarized in a paper and submitted to the journal of Nature Communication. I have further found that Pls enhance the ERK signaling through the G protein-coupled receptors (GPR1, GPR19, GPR21, GPR27 and GPR61). These data have already been published last year (Hossain MS et al., Plos One, e0150846, 2016). In addition, I have also published another paper in the Journal of Neuroscience recently (Hossain MS et al., J Neurosci. 37(15): 4074-4092, 2017.) describing our findings that the reduction of cellular Pls levels in the glial cells lead to the inflammation responses. In this study, I have explained in detail of how the GNPAT expression is reduced by inflammation, ageing and stress responses through the NF-kB and c-Myc. To the establishment of CRISPR-mediated knockout mice of the GPR19 and GPR61, I did not get any positive mice line. This could be due to the embryonic lethal effect of the knockout of these GPCRs. Further experiments are going on to demonstrate the possible interaction of Pls with the GPCRs and their biological role in the brain.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
To the establishment of CRISPR-mediated knockout mice of the GPR19 and GPR61, I did not get any positive mice line which was confirmed by genotyping and western blotting assays using tail tissue samples. This could be due to the embryonic lethal effect of the knockout of these GPCRs.
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| Strategy for Future Research Activity |
There will be no big changes in this project.
For the time being, I will do the best to establish the knockout mice of the orphan GPR 19 and 61.
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| Causes of Carryover |
Because of unexpected attendance in the international meeting, which was invited as a keynote speaker, the amount of travel expense became over to the planned amount of money. Then I tried to save money for reagents. As a result, small amount of money was even left and should be used next year.
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| Expenditure Plan for Carryover Budget |
I will use the left money from this year, because the next year is the last of this project.
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