2014 Fiscal Year Annual Research Report
| Project/Area Number |
25830007
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| Research Institution | University of Toyama |
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Principal Investigator |
SHEHATA Mohammad 富山大学, 大学院医学薬学研究部(医学), 助教 (60444197)
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Keywords | Autophagy / PTSD |
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| Outline of Annual Research Achievements |
Using immunoblotting of light chain protein 3 (LC3) and immunohistochemistry to detect autophagosomes in GFP-LC3 transgenic mice, we found that autophagy is induced in mouse hippocampus two hours after neuronal stimulation with electroconvulsive shock. Also, we found that the basal total GFP-LC3 signal in the GFP-LC3 transgenic mice is high in the central amygdala and the lateral baso-lateral amygdala, known to receive inhibitory inputs, compared to the medial baso-lateral amygdala, known to show increase in c-fos expression after fear memory. Collectively, these data imply that neuronal activity somehow regulates autophagy in vivo.
In addition, we injected an autophagy inducer (the tat-beclin1 peptide; Shoji-Kawata, et al., Nature, 2013) immediately after recall of contextual fear memory. Injection of autophagy inducers combined with anisomycin into CA1 region of the hippocampus does not further enhance anisomycin amnesic effect; however, it leads to a significant loss in context discrimination. Interestingly, anisomycin injection alone also shows some loss in context discrimination. Also, injection of the combination drugs into Amygdala enhanced anisomycin amnesic effect without any loss in context discrimination.
Our data is in line with our hypothesis that inducing protein degradation enhances memory destabilization. Also, these data suggests autophagy inducers to play a role in the treatment strategies for psychological diseases such as post-traumatic stress disorder (PTSD).
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