Jiangsu Key Laboratory of Neuroregeneration

Nantong, China

Jiangsu Key Laboratory of Neuroregeneration

Nantong, China
Time filter
Source Type

Li A.,Nantong University | Zou F.,Nantong University | Fu H.,Nantong University | Cui G.,Nantong University | And 3 more authors.
Journal of Molecular Neuroscience | Year: 2013

Traumatic brain injury (TBI) initiates a complex series of neurochemical and signaling changes that leads to neuronal dysfunction and over-reactive astrocytes. There is increasing evidence that CRM1 mediated P27Kip1, which is a potent inhibitor of G1 cyclin-dependent kinases complexes, nuclear export-dependent or -independent Jab1/CSN5, and cytoplasmic degradation in cells. Up to now, the function of CRM1 in central nervous system (CNS) is still with limited acquaintance. In our study, to investigate whether CRM1 is involved in CNS lesion, we performed a TBI model in adult rats. Western blot and RT-PCR analysis revealed that the level of protein and mRNA of CRM1 increased in ipsilateral brain cortex in comparison to the contralateral. Immunohistochemistry and immunofluorescence double labeling indicated that CRM1 was shutting into nucleus around the wound, and increased CRM1 co-localized with P27Kip1. Terminal deoxynucleotidyl transferase deoxy-UTP-nick end labeling (TUNEL) staining suggested that CRM1 was involved in neuronal apoptosis after brain injury. We also investigated co-localization of CRM1 and active-caspase-3 in the ipsilateral brain cortex. In addition, the expression patterns of Bax and active-caspase-3 were parallel with that of CRM1. Based on our data, we suggested that CRM1 might play an important role in neuronal apoptosis following TBI, and might provide a basis for the further study on its role in regulating the expression of P27Kip1 and cell cycle re-entry in TBI. © 2013 Springer Science+Business Media New York.

Xian H.,Nantong University | Zhao J.,Jiangsu Key Laboratory of Neuroregeneration | Zheng Y.,Jiangsu Key Laboratory of Neuroregeneration | Wang M.,Jiangsu Key Laboratory of Neuroregeneration | And 4 more authors.
Life Sciences | Year: 2014

Aims To investigate the anti-apoptotic effect of MADP, an analog of salidroside, against glutamate induced apoptosis in the cultured rat hippocampal neurons. Main methods Cytotoxicity was determined by the MTT method and lactate dehydrogenase release to the medium. Cell apoptosis was evaluated by Hoechst 33342 staining, TUNEL assay and flow cytometric analysis. Western blotting was applied for detecting protein levels of cellular signaling molecules. Key findings Our results showed that glutamate exposure significantly induces cell apoptosis, whereas the pretreatment of salidroside or MADP remarkably improves cell viability. Most importantly, the anti-apoptotic effect of MADP against glutamate insult is superior to salidroside. To explore the involved mechanisms, we measured some pro-apoptotic and anti-apoptotic protein levels, and several cell survival signaling pathways were analyzed as well. No visible alterations in Bcl-2 and Bax protein levels were observed by MADP or salidroside. Akt and JNK phosphorylation was robustly stimulated by MADP in the glutamate-treated neurons. Salidroside treatment results in a slight activation in Akt, while no significant alteration in JNK activity was observed. Significance MADP exhibits higher capacity to attenuate glutamate induced cell apoptosis in the cultured rat hippocampal neurons, suggesting that MADP might be a better candidate than salidroside for developing novel drugs treating neuron loss associated disorders. © 2014 Elsevier Inc.

Shi J.,Jiangsu Key Laboratory of Neuroregeneration | Shi J.,Nantong University | Qian W.,Jiangsu Key Laboratory of Neuroregeneration | Qian W.,Nantong University | And 9 more authors.
Journal of Biological Chemistry | Year: 2011

Hyperphosphorylation and deposition of tau into neurofibrillary tangles is a hallmark of Alzheimer disease (AD). Alternative splicing of tau exon 10 generates tau isoforms containing three or four microtubule binding repeats (3R-tau and 4R-tau), which are equally expressed in adult human brain. Dysregulation of exon 10 causes neurofibrillary degeneration. Here, we report that cyclic AMP-dependent protein kinase, PKA, phosphorylates splicing factor SRSF1, modulates its binding to tau pre-mRNA, and promotes tau exon 10 inclusion in cultured cells and in vivo in rat brain. PKA-Cα, but not PKA-Cβ, interacts with SRSF1 and elevates SRSF1-mediated tau exon 10 inclusion. In AD brain, the decreased level of PKA-Cα correlates with the increased level of 3R-tau. These findings suggest that a downregulation of PKA dysregulates the alternative splicing of tau exon 10 and contributes to neurofibrillary degeneration in AD by causing an imbalance in 3R-tau and 4R-tau expression. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc.

Qian W.,Jiangsu Key Laboratory of Neuroregeneration | Qian W.,Nantong University | Liang H.,Jiangsu Key Laboratory of Neuroregeneration | Shi J.,Jiangsu Key Laboratory of Neuroregeneration | And 7 more authors.
Nucleic Acids Research | Year: 2011

Abnormal alternative splicing of tau exon 10 results in imbalance of 3R-tau and 4R-tau expression, which is sufficient to cause neurofibrillary degeneration. Splicing factor SC35, a member of the superfamily of the serine/arginine-rich (SR) proteins, promotes tau exon 10 inclusion. The molecular mechanism by which SC35 participates in tau exon 10 splicing remains elusive. In the present study, we found that tau pre-mRNA was coprecipitated by SC35 tagged with HA. Mutation of the SC35-like exonic splicing enhancer located at exon 10 of tau affected both the binding of SC35 to tau pre-mRNA and promotion of tau exon 10 inclusion, suggesting that SC35 acts on the SC35-like exonic splicing enhancer to promote tau exon 10 inclusion. Dyrk1A (dual-specificity tyrosine-phosphorylated and regulated kinase 1A) phosphorylated SC35 in vitro and interacted with it in cultured cells. Overexpression of Dyrk1A suppressed SC35′s ability to promote tau exon 10 inclusion. Downregulation of Dyrk1A promoted 4R-tau expression. Therefore, upregulation of Dyrk1A in Down syndrome brain or Alzheimer's brain may cause dysregulation of tau exon 10 splicing through SC35, and probably together with other splicing factors, leading to the imbalance in 3R-tau and 4R-tau expression, which may initiate or accelerate tau pathology and cause neurofibrillary degeneration in the diseases. © 2011 The Author(s).

Su X.,Nantong University | Zhu C.-L.,Jiangsu Key Laboratory of Neuroregeneration | Shi W.,Nantong University | Ni L.-C.,Nantong University | And 2 more authors.
Journal of Molecular Histology | Year: 2012

MLTK (mixed-lineage kinase-like mitogen-activated protein triple kinase) is a member of the mitogen-activated protein kinase family and functioned as a mitogen activated kinase kinase kinase. MLTKα, one of the alternatively spliced forms of MLTK, could activate the c-Jun N-terminal kinase pathway, which involved in cellular stress responses and apoptosis. But the role of MLTKα in neural apoptosis was still unclear. Here, we performed a transient global cerebral ischemia model (TGCI) in adult rats and detected the dynamic changes of MLTKα in hippocampal CA1 neurons and brain cortex. We found the MLTKα expression was increased shortly after TGCI and peaked after 8 h. In spatial distribution, MLTKα was widely located in neurons rather than astrocytes and microglia. Moreover, there was a concomitant up-regulation of active caspase-3. Taken together, we hypothesized the up-regulation of MLTKα played an essential role in the apoptosis of hippocampal CA1 neurons. © Springer Science+Business Media B.V. 2012.

Liu X.-D.,Nantong University | Xue C.-B.,Jiangsu Key Laboratory of Neuroregeneration | Ju Q.-Q.,Nantong University | Yang X.-H.,Nantong University | And 4 more authors.
Acta Anatomica Sinica | Year: 2015

Objective To explore a method for construction of tissue engineered nerve grafts (Latin-engineered nerve grafts, TENGs) using silk fibroin/filament in vitro and to evaluate their roles for repairing spinal cord injury. Methods Isolation and induction of rat skin derived precursors into Schwann cells (SCs). S-l00 immunofluorescence histochemical staining was applied for the SCs identification. As seed cells, SCs differentiated from skin derived precursors (SKI's) cultured with silk fibroin conduit and silk filament scaffold in aUto. After culturing for 7 days, the TENGS were transplanted into the injury site of rat dorsal spinal cord (T8-T10) hemisection model. I3B13 score was evaluated at iliffprr,it time points after the operation. The spinal cord samples were obtained 8 weeks after the operation and immunofluorescence histochemical staining was applied to evaluate the regeneration of the injured spinal cord and the survival of seed cells. Results Under a phase contrast microscope, most of the seed cells were bipolar or tripolar. The immunofluorescence staining showed that SKP.SCs were S-lOO positive. After the transplantation of the TF.NGS into spinal cord injury site, BBB scores were significantly higher in TENGs group than in control group from 4 weeks to 8 weeks. The GFP-positive seed cells were also investigated after 8 weeks after the operation. Conclusion The TENGS constructed by silk fibroin/tilament including seed cells may promote repairing of rat spinal cord injury.

Loading Jiangsu Key Laboratory of Neuroregeneration collaborators
Loading Jiangsu Key Laboratory of Neuroregeneration collaborators