In this study, we used a rat model of severe closed traumatic brain injury to explore the relationship between neuroglobin, brain injury and neuronal apoptosis. Real-time PCR showed that neuroglobin mRNA expression ra...In this study, we used a rat model of severe closed traumatic brain injury to explore the relationship between neuroglobin, brain injury and neuronal apoptosis. Real-time PCR showed that neuroglobin mRNA expression rapidly increased in the rat cerebral cortex, and peaked at 30 minutes and 48 hours following traumatic brain injury. Immunohistochemical staining demonstrated that neuroglobin expression increased and remained high 2 hours to 5 days following injury. The rate of increase in the apoptosis-related Bax/Bcl-2 ratio greatly decreased between 30 minutes and 1 hour as well as between 48 and 72 hours post injury. Expression of neuroglobin and the anti-apoptotic factor Bcl-2 greatly increased, while that of the proapoptotic factor decreased, in the cerebral cortex post severe closed traumatic brain injury. It suggests that neuroglobin might protect neurons from apoptosis after traumatic injury by regulating Bax/Bcl-2 pathway.展开更多
BACKGROUND: Previous experiments have confirmed bone morphogenetic proteins (BMPs) upregulate cholinergic expression in neurons isolated from the embryonic rat hippocampus and cerebral cortex. Therefore, BMPs could...BACKGROUND: Previous experiments have confirmed bone morphogenetic proteins (BMPs) upregulate cholinergic expression in neurons isolated from the embryonic rat hippocampus and cerebral cortex. Therefore, BMPs could be useful for treating Alzheimer's disease and other neurodegenerative diseases. OBJECTIVE: BMP-4 was infused into the hippocampal dentate gyrus of fomix-fimbria transected rats to test the effects of BMP-4 on cholinergic expression in dentate gyrus neurons, and to observe changes in spatial memory behavior. DESIGN: A randomized controlled animal experiment. SETTING: Department of Neurosurgery and Laboratory for Cell Biology, Institute of Geriatrics, General Hospital of Chinese PLA. MATERIALS: Twenty-seven healthy adult male Sprague Dawley (SD) rats, weighing 250-300 g, were provided by the Laboratory Animal Center of the General Hospital of Chinese PLA. Reagents: BMP-4 (B-2680, Sigma Company) and choline acetyl transferase (CHAT) antibody (AB5042, Chemicon Company) were used in this study. Equipments: a rat stereotaxic instrument (type: SN-2N, Narushige Group, Japan) and Image-prog-plus image analysis software (Media Cybernetics company, USA) were used in this study. The protocol was carried out in accordance with ethical guidelines for the use and care of animals. METHODS: This experiment was performed in the Institute of Geriatrics, General Hospital of Chinese PLA between July 2004 and March 2005. Rats were randomly divided into 4 groups: Alzheimer's disease group (n = 7), normal control group (n = 5), BMP-4-Alzheimer's disease group (n = 8), and model group (n = 7). In the Alzheimer's disease group, the left hippocampal fomix-fimbria of rats was transected to mimic Alzheimer's disease symptoms. In the BMP-4-Alzheimer's disease group, 1 μt L BMP-4 (10 mg/L) was perfused into the left dentate gyrus with a microinjector at 1 μ L/min. In the model group, 1 μ L saline was perfused into the same position by the same method. Twenty-eight days after injection, Morris water maze test was performed in all rats to test spatial memory. Time-to-platform and swim-path length were recorded. Immunohistochemical staining of cholinergic neurons was performed on brain sections containing dentate gyrus. The area covered by ChAT-positive cells was analyzed using an Image-prog-plus image analysis software. MAIN OUTCOME MEASURES: Area covered by ChAT-positive cells in the dentate gyrus. Time-to-platform and swim path-length. RESULTS: Twenty-seven rats were included in the final analysis. In the Alzheimer's disease group, the area covered by ChAT-positive cells was significantly smaller compared with the normal control group (F = 76.03, P 〈 0.01). The area covered by ChAT-positive cells was significantly larger in the BMP-4- Alzheimer's disease group than in the model group (F = 35.17, P 〈 0.05), but significantly smaller than in the normal control group (F = 40.17, P 〈 0.05). Time-to-platform and swim-path length were significantly longer in the Alzheimer's disease group than in the normal control group (F =24.62 and 631.58, respectively, both P 〈 0.05). Time-to-platform and swim-path length were significantly shorter in the BMP4-Alzheimer's disease group compared with the model group (F= 22.06 and 606.89, respectively P 〈 0.05). CONCLUSION: Injection of BMP-4 into the dentate gyrus of Alzheimer's disease model rats alleviates central cholinergic system injury and concomitantly improves spatial memory.展开更多
基金supported by General Program of National Natural Science Foundation of China,No. 30400465,30571903Open Project from Medical Neurobiology of State Key Laboratory (09-08) of Fudan University
文摘In this study, we used a rat model of severe closed traumatic brain injury to explore the relationship between neuroglobin, brain injury and neuronal apoptosis. Real-time PCR showed that neuroglobin mRNA expression rapidly increased in the rat cerebral cortex, and peaked at 30 minutes and 48 hours following traumatic brain injury. Immunohistochemical staining demonstrated that neuroglobin expression increased and remained high 2 hours to 5 days following injury. The rate of increase in the apoptosis-related Bax/Bcl-2 ratio greatly decreased between 30 minutes and 1 hour as well as between 48 and 72 hours post injury. Expression of neuroglobin and the anti-apoptotic factor Bcl-2 greatly increased, while that of the proapoptotic factor decreased, in the cerebral cortex post severe closed traumatic brain injury. It suggests that neuroglobin might protect neurons from apoptosis after traumatic injury by regulating Bax/Bcl-2 pathway.
文摘BACKGROUND: Previous experiments have confirmed bone morphogenetic proteins (BMPs) upregulate cholinergic expression in neurons isolated from the embryonic rat hippocampus and cerebral cortex. Therefore, BMPs could be useful for treating Alzheimer's disease and other neurodegenerative diseases. OBJECTIVE: BMP-4 was infused into the hippocampal dentate gyrus of fomix-fimbria transected rats to test the effects of BMP-4 on cholinergic expression in dentate gyrus neurons, and to observe changes in spatial memory behavior. DESIGN: A randomized controlled animal experiment. SETTING: Department of Neurosurgery and Laboratory for Cell Biology, Institute of Geriatrics, General Hospital of Chinese PLA. MATERIALS: Twenty-seven healthy adult male Sprague Dawley (SD) rats, weighing 250-300 g, were provided by the Laboratory Animal Center of the General Hospital of Chinese PLA. Reagents: BMP-4 (B-2680, Sigma Company) and choline acetyl transferase (CHAT) antibody (AB5042, Chemicon Company) were used in this study. Equipments: a rat stereotaxic instrument (type: SN-2N, Narushige Group, Japan) and Image-prog-plus image analysis software (Media Cybernetics company, USA) were used in this study. The protocol was carried out in accordance with ethical guidelines for the use and care of animals. METHODS: This experiment was performed in the Institute of Geriatrics, General Hospital of Chinese PLA between July 2004 and March 2005. Rats were randomly divided into 4 groups: Alzheimer's disease group (n = 7), normal control group (n = 5), BMP-4-Alzheimer's disease group (n = 8), and model group (n = 7). In the Alzheimer's disease group, the left hippocampal fomix-fimbria of rats was transected to mimic Alzheimer's disease symptoms. In the BMP-4-Alzheimer's disease group, 1 μt L BMP-4 (10 mg/L) was perfused into the left dentate gyrus with a microinjector at 1 μ L/min. In the model group, 1 μ L saline was perfused into the same position by the same method. Twenty-eight days after injection, Morris water maze test was performed in all rats to test spatial memory. Time-to-platform and swim-path length were recorded. Immunohistochemical staining of cholinergic neurons was performed on brain sections containing dentate gyrus. The area covered by ChAT-positive cells was analyzed using an Image-prog-plus image analysis software. MAIN OUTCOME MEASURES: Area covered by ChAT-positive cells in the dentate gyrus. Time-to-platform and swim path-length. RESULTS: Twenty-seven rats were included in the final analysis. In the Alzheimer's disease group, the area covered by ChAT-positive cells was significantly smaller compared with the normal control group (F = 76.03, P 〈 0.01). The area covered by ChAT-positive cells was significantly larger in the BMP-4- Alzheimer's disease group than in the model group (F = 35.17, P 〈 0.05), but significantly smaller than in the normal control group (F = 40.17, P 〈 0.05). Time-to-platform and swim-path length were significantly longer in the Alzheimer's disease group than in the normal control group (F =24.62 and 631.58, respectively, both P 〈 0.05). Time-to-platform and swim-path length were significantly shorter in the BMP4-Alzheimer's disease group compared with the model group (F= 22.06 and 606.89, respectively P 〈 0.05). CONCLUSION: Injection of BMP-4 into the dentate gyrus of Alzheimer's disease model rats alleviates central cholinergic system injury and concomitantly improves spatial memory.