Induction of long-term potentiation at Schaffer collateral-CA1 synapses in mice hippocampus after IMPX977 administration
Objective To investigate the effects of IMPX977 on long term potentiation (LTP) at Schaffer collateral-CA1 synapses in vitro and on methyl CpG binding protein 2 (Mecp2) expression in mice cortex and hippocampus. Methods Thirty-two C57BL/6 mice were randomly divided into four groups: control, olive oil (vehicle), IMPX977 low (5 mg/kg) and high (15 mg/kg) groups. Mice were administrated every other day orally for two weeks. Extracellular recording technique in vitro was used to record the effects of IMPX977 on Schaffer collateral-CA1 LTP pathway in acute mice hippocampal slices. The Mecp2 protein expression level was detected by Western blotting. Results Compared to the control group, vehicle did not alter the synaptic transmission in Schaffer collateral-CA1 synapses, however, IMPX977 at concentrations of 5 mg/kg and 15 mg/kg significantly enhanced fEPSP (field excitatory postsynaptic potential) slope in Schaffer collateral-CA1 pathway to (179.6 ± 17.8)% and (191.4 ± 21.4)%, individually 60 min after HFS, IMPX977 improved LTP induction significantly at Schaffer collateral-CA1 pathway at least. Also, IMPX977 significantly elevated MeCP2 protein level in cortex and hippocampus. Conclusion The effects of IMPX977 on synaptic transmission and Mecp2 protein expression provided convincing evidence that IMPX977 could be promising new drug candidates for Rett syndrome treatment.
We are grateful to Guangzhou Science Technology and Innovation Commission Technology Research Projects (No. 201805010005), Scientific Research Common Program of Beijing Municipal Commission of Education (No. KM201 100250) and the National Natural Science Foundation of China (No. 81073137) for financial support of this project.
Ni Song b, Chen Duan a, Ye Li c, Tian-xiu Qian a, Qi Wang b, Wei Zhao b, Xiao-ying Wang a. Induction of long-term potentiation at Schaffer collateral-CA1 synapses in mice hippocampus after IMPX977 administration[J]. Chinese Herbal Medicines (CHM),2021,13(1):
Online Published: January 18,2021
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