title: Neurotropin® alleviates hippocampal neuron damage through a HIF-1α/MAPK pathway.
abstract: OBJECTIVE
  The main purpose was to verify the potent capacity of Neurotropin® against neuronal damage in hippocampus and to explore its underlying mechanisms.
  
  
  METHODS
  HT22 cells were treated with 40 μmol/L Aβ25-35in 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/PS1 mice after Neurotropin® treatment. The expression of proteins, including HIF-1α, Bcl-2, Bax, and MAPKs signaling molecules was evaluated by Western blot.
  
  
  RESULTS
  Neurotropin® significantly reversed the cell injury induced by Aβ25-35through increasing cell viability and mitochondrial membrane potential, decreasing intracellular ROS and cell apoptosis of HT22 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-ERK1/2, p-JNK, and p-P38 was significantly inhibited in hippocampus of APP/PS1 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.
authors.affiliation: Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Wen-Li
authors.initials: WL
authors.lastname: Fang
authors.affiliation: Department of Neurology, Nanfang Hospital Huiqiao Medical Center, Guangzhou, Guangdong, China.
authors.forename: De-Qiang
authors.initials: DQ
authors.lastname: Zhao
authors.affiliation: Department of Anesthesiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Sheng-Nuo
authors.initials: SN
authors.lastname: Fan
authors.affiliation: Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Wang
authors.initials: W
authors.lastname: Liao
authors.affiliation: Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Yu-Qiu
authors.initials: YQ
authors.lastname: Zheng
authors.affiliation: Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Shao-Wei
authors.initials: SW
authors.lastname: Liao
authors.affiliation: Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Song-Hua
authors.initials: SH
authors.lastname: Xiao
authors.affiliation: Medicine School, Shenzhen University, Shenzhen, Guangdong, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Luan
authors.affiliation: Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.|Laboratory of RNA and Major Diseases of Brain and Heart, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.|Guangdong Province Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Jun
authors.identifier: http://orcid.org/0000-0001-9202-5878
authors.initials: J
authors.lastname: Liu
mesh_terms: D016229:Amyloid beta-Peptides / Q000235:genetics / Q000633:toxicity; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000235:genetics / Q000633:toxicity; D058225:Plaque, Amyloid / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D011134:Polysaccharides / Q000494:pharmacology*; D011897:Random Allocation; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D011134:Polysaccharides; D017382:Reactive Oxygen Species; C074636:amyloid beta-protein (25-35); C010491:neurotropin
keywords: Alzheimer's disease; HIF-1α/MAPK signaling; neuroprotective effect; neurotropin®