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Advanced Neurology                                      Dysregulation of cAMP signaling pathway in MT2KO mice




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            Figure 5. Perturbations of cAMP/PKA/CREB signaling pathway. (A) Western blot of CREB133 and total CREB. (B) Relative quantification of CREB133 and
            total CREB. **P < 0.01, compared with C3H mice;  P < 0.01; compared with MT2KO. (C) Western blot for PKAα and PKAβ. (D) Relative quantification of
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            PKAα and PKAβ. *P < 0.05 and **P < 0.01, compared with C3H mice. (E) Detection of PKA activity by ELISA. *P < 0.05 and **P < 0.01, compared with
            C3H mice. (F) The quantification of cAMP by ELISA. *P < 0.05, compared with C3H mice. (G) The quantification of cGMP by ELISA. (H) Western blot
            of EPAC2 and EPAC1. (I) Relative quantification of EPAC2 and EPAC1. *P < 0.05, compared with C3H mice;  P < 0.01, compared with MT2KO mice.
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            Abbreviations: CREB: cAMP-responsive element binding protein; PKAα: Protein kinase A  α; PKAβ: Protein kinase A  β; cGMP: Cyclic guanosine
            monophosphate; EPAC2: cAMP-regulated guanine nucleotide exchange factor II; ELISA: Enzyme-linked immunosorbent assay; MT2KO: Melatonin
            receptor 2 knockout.
            MT1KO mice. It was known that PKA was the substrate of   an important role in MT knockout mice, consistent with
            cAMP, and different concentration of cAMP has different   the behavior of the mice. Our results showed a slight but
            effects on the substrate. This suggested that the different   significant decrease in EPAC2 expression in MT2KO mice,
            concentrations of cAMP may lead to different effects on   and it has been shown that EPAC2 reduces GluR2/3 protein
            the activity of PKA. The cAMP/PKA/CREB pathway plays   content in synapses, and this effect was not dependent on



            Volume 2 Issue 3 (2023)                         8                         https://doi.org/10.36922/an.0974
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