X-box-binding protein 1-transfected neural stem cells were transplanted into the right lateral ventricles of rats with rotenone-induced Parkinson＇s disease. The survival capacities and differentiation rates of cells ...X-box-binding protein 1-transfected neural stem cells were transplanted into the right lateral ventricles of rats with rotenone-induced Parkinson＇s disease. The survival capacities and differentiation rates of cells expressing the dopaminergic marker tyrosine hydroxylase were higher in X-box-binding protein 1-transfected neural stem cells compared to non-transfected cells. Moreover, dopamine and 3,4-dihydroxyphenylacetic acid levels in the substantia nigra were significantly increased, α-synuclein expression was decreased, and neurological behaviors were significantly ameliorated in rats following transplantation of X-box-binding protein 1-transfected neural stem cells. These results indicate that transplantation of X-box-binding protein 1-transfected neural stem cells can promote stem cell survival and differentiation into dopaminergic neurons, increase dopamine and 3,4-dihydroxyphenylacetic acid levels, reduce α-synuclein aggregation in the substantia nigra, and improve the symptoms of Parkinson＇s disease in rats.展开更多
X-box-binding protein-1 （XBP-1） is an essential transcription factor in endoplasmic reticulum stress In this study, XBP-1 gene-transfected neural stem cells （NSCs） were transplanted into lesion sites to ensure sta...X-box-binding protein-1 （XBP-1） is an essential transcription factor in endoplasmic reticulum stress In this study, XBP-1 gene-transfected neural stem cells （NSCs） were transplanted into lesion sites to ensure stability and persistent expression of XBP-1, resulting in the exertion of anti-apoptotic effects. Simultaneously, XBP-1 gene transfection promotes the survival and differentiation of transplanted NSCs. Results from this study demonstrated that survival, proliferation and differentiation of XBP-1 g^ne-modified NSCs were enhanced when compared to unmodified NSCs at 28 days post-transplantation （P 〈 0.05）. A diminished number of apoptotic neural cells increased Bcl-2 expression and reduced Bax expression, and were observed in the ischemic region of the XBP-1-NSCs group （P 〈 0.05）. These results indicated that modification of the XBP-1 gene enhances the survival and migration of NSCs in vivo and decreases the occurrence of apoptosis.展开更多
BACKGROUND： Alpha-actinin （ a -actinin） plays a key role in neuronal growth cone migration during directional differentiation from neural stem cells （NSCs） to neurons. OBJECTIVE： To detect in situ microdistribut...BACKGROUND： Alpha-actinin （ a -actinin） plays a key role in neuronal growth cone migration during directional differentiation from neural stem cells （NSCs） to neurons. OBJECTIVE： To detect in situ microdistribution and quantitative expression of a -actinin during directional differentiation of NSCs to neurons in the temporal lobe cerebral cortex of neonatal rats. DESIGN, TIME AND SETTING： Between January 2006 and December 2008, culture and directional differentiation of NSCs were performed at Department of Histology and Embryology, Preclinical Medical College, China Medical University. Immune electron microscopy was performed at Department of Histology and Embryology and Department of Electron Micrology, Preclinical Medical College, China Medical University. Spectrum analysis was performed at Laboratory of Electron Microscopy, Mental Research Institute, Chinese Academy of Sciences. MATERIALS： Basic fibroblast growth factor, epidermal growth factor, brain-derived nerve growth factor, type-1 insulin like growth factor, and a -actinin antibody were provided by Gibco BRL, USA; rabbit-anti-rat nestin monoclonal antibody, rabbit-anti-rat neuron specific enolase polyclonal antibody, and EDAX-9100 energy dispersive X-ray analysis were provided by PHILIPS Company, Netherlands. METHODS： NSCs, following primary and passage culture, were differentiated with serum culture medium （DMEM/F12 ＋ 10% fetal bovine serum ＋ 2 ng/mL brain-derived nerve growth factor ＋ 2 ng/mL type-1 insulin like growth factor）. MAIN OUTCOME MEASURES： Expression of a -actinin in neuron-like cells was quantitatively and qualitatively detected with immunocytochemistry using energy dispersive X-ray analysis. RESULTS： Immunocytochemistry, combined with electron microscopy, indicated that positive α -actinin expression was like a spheroid particle with high electron density. In addition, the expression was gradually concentrated from the nuclear edge to the cytoplasm and expanded into developing neurites, during differentiation of neural stem cells to neurons. Conversely, energy dispersive X-ray analysis indicated that the more mature the neural differentiation was, and the greater the expression of α -actinin. CONCLUSION： The gradual increase of α -actinin expression is related to growth, development, and maturity of differentiated neuron-like cells, in neonatal rat frontal lobe cortex, at different differentiating time points of NSCs to neurons.展开更多
文摘X-box-binding protein 1-transfected neural stem cells were transplanted into the right lateral ventricles of rats with rotenone-induced Parkinson＇s disease. The survival capacities and differentiation rates of cells expressing the dopaminergic marker tyrosine hydroxylase were higher in X-box-binding protein 1-transfected neural stem cells compared to non-transfected cells. Moreover, dopamine and 3,4-dihydroxyphenylacetic acid levels in the substantia nigra were significantly increased, α-synuclein expression was decreased, and neurological behaviors were significantly ameliorated in rats following transplantation of X-box-binding protein 1-transfected neural stem cells. These results indicate that transplantation of X-box-binding protein 1-transfected neural stem cells can promote stem cell survival and differentiation into dopaminergic neurons, increase dopamine and 3,4-dihydroxyphenylacetic acid levels, reduce α-synuclein aggregation in the substantia nigra, and improve the symptoms of Parkinson＇s disease in rats.
文摘X-box-binding protein-1 （XBP-1） is an essential transcription factor in endoplasmic reticulum stress In this study, XBP-1 gene-transfected neural stem cells （NSCs） were transplanted into lesion sites to ensure stability and persistent expression of XBP-1, resulting in the exertion of anti-apoptotic effects. Simultaneously, XBP-1 gene transfection promotes the survival and differentiation of transplanted NSCs. Results from this study demonstrated that survival, proliferation and differentiation of XBP-1 g^ne-modified NSCs were enhanced when compared to unmodified NSCs at 28 days post-transplantation （P 〈 0.05）. A diminished number of apoptotic neural cells increased Bcl-2 expression and reduced Bax expression, and were observed in the ischemic region of the XBP-1-NSCs group （P 〈 0.05）. These results indicated that modification of the XBP-1 gene enhances the survival and migration of NSCs in vivo and decreases the occurrence of apoptosis.
基金Supported by:the National Natural Science Foundation of China,No.39970383the Project for Science and Technology from Educational Committee of Liaoning Province,No.202013132Technological Program for Colleges and Universities of Liaoning Educational Committee,No.[2008]84
文摘BACKGROUND： Alpha-actinin （ a -actinin） plays a key role in neuronal growth cone migration during directional differentiation from neural stem cells （NSCs） to neurons. OBJECTIVE： To detect in situ microdistribution and quantitative expression of a -actinin during directional differentiation of NSCs to neurons in the temporal lobe cerebral cortex of neonatal rats. DESIGN, TIME AND SETTING： Between January 2006 and December 2008, culture and directional differentiation of NSCs were performed at Department of Histology and Embryology, Preclinical Medical College, China Medical University. Immune electron microscopy was performed at Department of Histology and Embryology and Department of Electron Micrology, Preclinical Medical College, China Medical University. Spectrum analysis was performed at Laboratory of Electron Microscopy, Mental Research Institute, Chinese Academy of Sciences. MATERIALS： Basic fibroblast growth factor, epidermal growth factor, brain-derived nerve growth factor, type-1 insulin like growth factor, and a -actinin antibody were provided by Gibco BRL, USA; rabbit-anti-rat nestin monoclonal antibody, rabbit-anti-rat neuron specific enolase polyclonal antibody, and EDAX-9100 energy dispersive X-ray analysis were provided by PHILIPS Company, Netherlands. METHODS： NSCs, following primary and passage culture, were differentiated with serum culture medium （DMEM/F12 ＋ 10% fetal bovine serum ＋ 2 ng/mL brain-derived nerve growth factor ＋ 2 ng/mL type-1 insulin like growth factor）. MAIN OUTCOME MEASURES： Expression of a -actinin in neuron-like cells was quantitatively and qualitatively detected with immunocytochemistry using energy dispersive X-ray analysis. RESULTS： Immunocytochemistry, combined with electron microscopy, indicated that positive α -actinin expression was like a spheroid particle with high electron density. In addition, the expression was gradually concentrated from the nuclear edge to the cytoplasm and expanded into developing neurites, during differentiation of neural stem cells to neurons. Conversely, energy dispersive X-ray analysis indicated that the more mature the neural differentiation was, and the greater the expression of α -actinin. CONCLUSION： The gradual increase of α -actinin expression is related to growth, development, and maturity of differentiated neuron-like cells, in neonatal rat frontal lobe cortex, at different differentiating time points of NSCs to neurons.
