Open AccessNeurotropin® alleviates hippocampal neuron damage through a HIF ‐1α/ MAPK pathway
Author(s) -
Fang WenLi,
Zhao DeQiang,
Wang Fei,
Li Mei,
Fan ShengNuo,
Liao Wang,
Zheng YuQiu,
Liao ShaoWei,
Xiao SongHua,
Luan Ping,
Liu Jun
Publication year - 2017
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12689
Subject(s) - viability assay , neuroprotection , mapk/erk pathway , apoptosis , chemistry , intracellular , hippocampal formation , p38 mitogen activated protein kinases , microbiology and biotechnology , oxidative stress , western blot , cell damage , hippocampus , cell , signal transduction , pharmacology , biology , biochemistry , neuroscience , gene
Summary Aims The main purpose was to verify the potent capacity of Neurotropin® against neuronal damage in hippocampus and to explore its underlying mechanisms. Methods HT 22 cells were treated with 40 μmol/L Aβ 25‐35 in the presence of various concentrations of Neurotropin® or in its absence. The cell viability was assessed with a CCK ‐8 assay, and flow cytometry was used to measure cell apoptosis, intracellular ROS levels, and mitochondrial membrane potential. Aβ plaques were examined by Bielschowsky silver staining, and the activities of antioxidants were detected in hippocampus of APP / PS 1 mice after Neurotropin® treatment. The expression of proteins, including HIF ‐1α, Bcl‐2, Bax, and MAPK s signaling molecules was evaluated by Western blot. Results Neurotropin® significantly reversed the cell injury induced by Aβ 25‐35 through increasing cell viability and mitochondrial membrane potential, decreasing intracellular ROS and cell apoptosis of HT 22 cells ( P <.05). Furthermore, Neurotropin® markedly reduced the formation of Aβ plaques and upregulated the activities of antioxidants ( P <.05). Additionally, the protein expression of HIF ‐1α, p‐ ERK 1/2, p‐ JNK , and p‐P38 was significantly inhibited in hippocampus of APP / PS 1 mice. Conclusions Neurotropin® exhibited a potent neuroprotective effect on inhibiting Aβ‐induced oxidative damage and alleviating Aβ deposition in hippocampus via modulation of HIF ‐1α/ MAPK signaling pathway.