Wen-Li Fang1, De-Qiang Zhao2, Fei Wang3, Mei Li1, Sheng-Nuo Fan1, Wang Liao1, Yu-Qiu Zheng1, Shao-Wei Liao1, Song-Hua Xiao1, Ping Luan4, Jun Liu1,5,6. 1. Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China. 2. Department of Neurology, Nanfang Hospital Huiqiao Medical Center, Guangzhou, Guangdong, China. 3. Department of Anesthesiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China. 4. Medicine School, Shenzhen University, Shenzhen, Guangdong, China. 5. Laboratory of RNA and Major Diseases of Brain and Heart, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China. 6. Guangdong Province Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China.
Abstract
AIMS: 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 Aβ25-35 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/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 Aβ25-35 through 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.
AIMS: 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 Aβ25-35 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/PS1mice 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 Aβ25-35 through 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/PS1mice. 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: S Hauptmann; I Scherping; S Dröse; U Brandt; K L Schulz; M Jendrach; K Leuner; A Eckert; W E Müller Journal: Neurobiol Aging Date: 2008-03-04 Impact factor: 4.673
Authors: I Daniel Limón; Alfonso Díaz; Liliana Mendieta; Germán Chamorro; Blanca Espinosa; Edgar Zenteno; Jorge Guevara Journal: Neurosci Res Date: 2008-11-25 Impact factor: 3.304