Early profiles of axonal growth and astroglial response after spinal cord hemisection and implantation of Schwann cell-seeded guidance channels in adult rats

We previously demonstrated that transplantation of Schwann cell-seeded channels promoted the regrowth of injured axons in the adult spinal cord. It is not clear, however, whether injured axons recapitulate the developmental scenarios to accomplish regeneration. In the present study, we investigated the early events associated with axonal regrowth after spinal cord hemisection at the eighth thoracic level and implantation of a Schwann cell-seeded minichannel in adult rats. Animals were sacrificed at postoperative days (PO) 2, 4, 7, and 14. Anterograde tracing with fluoro-ruby showed that regenerating axons grew into the graft prior to PO2 and reached the distal end of the channel at PO7. These axons expressed both embryonic neural cell adhesion molecule (E-NCAM) and growth associated protein-43 (GAP-43). Although the expression of E-NCAM decreased by PO7, that of GAP-43 remained high throughout the first 2 weeks after implantation. A close relation of vimentin-positive astroglia to the growing axons in the host tissue suggested a contact-mediated role of these cells in axon guidance. Aggregation of glial fibrillary acidic protein (GFAP)-positive astrocytes together with the increased expression of chondroitin sulfate proteoglycans (CSPGs) starting at PO7 appeared to inhibit axonal growth at the host-graft interface. Thus, adult regenerating axons and astroglia do express developmentally related molecules that may facilitate axonal growth into a permissive graft at the early phase of injury and regeneration. These results suggest that molecules and astroglia essential to development are both important in influencing axonal regrowth in the adult spinal cord.     

Neural cell adhesion molecule and perineural invasion in gallbladder cancer

To clarify the role of neural cell adhesion molecule (NCAM) in perineural invasion, NCAM expression was studied by immunohistochemical staining in 26 cases with gallbladder cancer. In gallbladder cancer, the incidence of perineural invasion and that of positive NCAM expression was 42% and 31%, respectively, which are less frequent than those of bile duct cancer in our previous report. Perineural invasion was observed in 88% of the patients with positive expression of NCAM and in 22% of those with negative expression. The former is similar to that of bile duct cancer but the latter is significantly lower. Eighty percent of the cancer cells that invaded the perineural space were positive for NCAM, when the primary tumor was positive for NCAM expression. Therefore, in gallbladder cancer, positive cells in NCAM expression likely invade the perineural spaces. However, the perineural invasion of negative cells in NCAM expression is not likely to occur as compared to bile duct cancer. In conclusion, perineural invasion in gallbladder cancer is not as common as in bile duct cancer, but the role of NCAM in perineural invasion is more important in gallbladder cancer than in bile duct cancer. © 1995 Wiley-Liss, Inc.     

尼莫地平对缺血性脑损伤大鼠神经细胞黏附分子表达的影响

目的探索缺血性脑损伤后,尼莫地平(Nimodipine,NDP)对大鼠神经再塑过程中神经细胞黏附分子(neural celladhesion molecule,NCAM)表达的影响。方法Wistar大鼠100只,随机分成假手术对照组(sham operation control group,SOCG,n=10)、脑缺血对照组(cerebral ischemia controlgroup,CICG,1、3、7d,n=10),脑缺血高、低剂量尼莫地平治疗组(nimodipine treatment group,H-NTG,L-NTG,1、3、7d,n=10)。手术阻断CICG和NTG右侧大脑中动脉,制造缺血性脑损伤模型,NTG腹腔注射NDP(0.5mg·kg-1和1mg·kg-1)。分别于1、3和7 d脑血流再灌注,神经功能缺损评分、局部脑血流量(regional cerebral blood flow,RCBF)测定后取材,观察大脑表面血管形态,检测NCAM的表达。结果H-NTG 3d和7d的PO2高于CICG(P<0.05或P<0.01);L-NTG和H-NTG的神经功能缺损评分低于CICG(P<0.05或P<0.01),其RCBF的灌注单位和NCAM的表达也高于CICG(P<0.05或P<0.01)。结论尼莫地平能改善缺血脑损伤大鼠的神经功能,增加局部脑血流量,缩小缺血脑组织梗死面积,促进NCAM的表达。     

Depression-like behaviour in neural cell adhesion molecule (NCAM)-deficient mice and its reversal by an NCAM-derived peptide, FGL

The neural cell adhesion molecule (NCAM) plays a pivotal role in brain plasticity. Brain plasticity itself has a crucial role in the development of depression. The aim of this study was to analyze whether NCAM-deficient (NCAM(-/-)) mice exhibit depression-like behaviour and whether a peptide termed FGL, derived from the NCAM binding site for the fibroblast growth factor (FGF) receptor, is able to reverse the depression-like signs in NCAM(-/-) mice. Our study showed that NCAM(-/-) mice demonstrated increased freezing time in the tail-suspension test and reduced preference for sucrose consumption in the sucrose preference test, reduced adult neurogenesis in the dentate gyrus and reduced levels of the phosphorylated cAMP response element-binding protein (pCREB) in the hippocampus. FGL administered acutely or repeatedly reduced depression-like behaviour in NCAM(-/-) mice without having an effect on their wild-type littermates. Repeated administration of FGL enhanced survival of the newly born neurons in NCAM(-/-) mice and increased the levels of pCREB in both NCAM(+/+) and NCAM(-/-) mice. In conclusion, our data demonstrate that NCAM deficiency in mice results in a depression-like phenotype which can be reversed by the acute or repeated administration of FGL. The results also suggest a role of the deficit in NCAM signalling through the FGF receptor in depression.     

突触可塑性与相关蛋白研究进展

神经生长相关蛋白 (neuronal growthassociatedprotein ,GAP 43)和神经细胞黏附因子 (neuralcelladhesionmolecule ,NCAM )与突触可塑性密切相关。GAP 43是一种神经细胞膜上的特异性磷蛋白 ,在神经发育和再生过程中呈现高表达 ,被作为突触生长的标志物。GAP 43与CaM结合 ,参与G蛋白相互作用 ,神经递质的释放 ,作用于胞吞 /胞吐过程 ,通过小囊溶合或诱导生长锥和突触前末端的胞吞促进膜扩展 ,与海马长时程增强密切相关。神经细胞黏附因子是细胞表面糖蛋白大家族的成员之一 ,促进轴突生长 ,对长时记忆的保持有重要影响 ,同时 ,GAP 43对其具调节作用     

三种胚胎期药物诱导大鼠隐睾模型的神经细胞黏附分子(NCAM)表达比较

目的:探讨邻苯二酸二丁酯(DBP)、己烯雌酚(DES)、氟他胺(Flu)宫内诱导SD鼠隐睾对生殖母细胞(Go)发育的影响。方法:SD孕鼠于妊娠12~21 d每日给予Flu(25 mg/kg,n=15)、DES(1.5μg/kg,n=15)皮下注射,DBP(500 mg/kg,n=10)灌胃,仔鼠出生后第1、10、20、80日取仔鼠睾丸组织,通过免疫组织化学及RT-PCR检测神经母细胞黏附分子(neural cell adhesion molecule,NCAM)在睾丸中的表达差异。结果:DES、DBP诱导大鼠曲细精管NCAM表达与玉米油溶剂对照(n=6)和空白对照组(n=6)一致,出生后第1日(PD1)曲细精管管腔内生殖母细胞(Go)位于管腔中央且均呈阳性表达;PD10 Go迁移至基底膜,NCAM表达明显减弱至消失;PD20、PD80隐睾及下降睾丸曲细精管内NCAM阴性表达。Flu诱导PD10及PD20、PD80隐睾组织中可见位于管腔中央的Go残留,NCAM呈阳性表达;RT-PCR结果显示Flu诱导PD10仔鼠睾丸及PD20隐睾的NCAM mRNA表达显著高于2个对照组(P<0.05)。结论:仅Flu诱导的隐睾组织在各时间段均可见Go残留,且NCAM mRNA及蛋白质表达显著高于正常组,该模型更适宜于研究隐睾Go发育缺陷。     

Maternal exposure to bisphenol A may increase the risks of Parkinson’s disease through down-regulation of fetal IGF-1 expression

So far, the pathogenesis of Parkinson’s disease (PD) remains unclear. Current studies implicate environmental toxins may be potential causes of fetal origin of PD. BPA is a member of the family of estrogenic chemicals existing widely in environment. Significant evidences from animal experimentation have demonstrated that BPA interfere with fetal neurodevelopment. Based on previous reports and our research on EB derived from hESCs, we speculate that maternal exposure to low-dose BPA during gestational period may decrease IGF-1 expression, thus hinder the development of fetal DA neurons, and finally increase the risks of fetal origin of PD. Our hypothesis may shed new light on the pathogenesis of PD and lead to potential preventive treatments.     

抑胶素对大鼠脑胶质瘤神经细胞粘附分子作用的体内试验研究

目的研究抑胶素对大鼠脑胶质瘤模型的抑瘤效应及对神经细胞粘附分子（NCAM）的影响。方法在Wistar大鼠脑尾状核接种C6细胞，观察大鼠的生存状态，给药7天后观察肿瘤体积变化及抑胶素、顺铂对鼠脑胶质瘤作用的形态学变化，应用免疫组织化学方法检测应用抑胶素前后对鼠脑胶质瘤神经细胞粘附分子的影响。结果实验组大鼠有较好的生存状态，经抑胶素治疗后可见肿瘤内神经细胞粘附分子阳性细胞密度增加，神经细胞粘附分子随浓度增加阳性率呈上升趋势。结论抑胶素是通过抑制胶质细胞瘤生长，提高神经细胞活性，从而抑制恶性胶质瘤细胞体外侵袭能力。     

Primary Ewing sarcoma of the axis-C2: A case report and the review of the literature

Introduction

Neck pain and torticollis are common symptoms in the pediatric population that rarely requires further investigation. However, in case symptoms persist, then a more meticulously approach should be considered. Underlying conditions such as infections, neck injury, autoimmune disorders or even cervical spine cancer should be excluded from diagnosis. Cervical spine cancer is a rare neurosurgical entity in the pediatric population and even rarer is atlantoaxial Ewing's sarcoma. In this report, we present a rare case of primary Ewing's sarcoma of the axis.

ELF1 suppresses autophagy to reduce cisplatin resistance via the miR-152-3p/NCAM1/ERK axis in lung cancer cells

Resistance to chemotherapeutic drugs limits the efficacy of chemotherapy in non–small cell lung cancer (NSCLC). Autophagy is an essential mechanism which involves in drug resistance. Our previous research has revealed that miR-152-3p represses NSCLC progression. However, the mechanism of miR-152-3p in autophagy-mediated chemoresistance in NSCLC remains unclear. Cisplatin-resistant cell lines (A549/DDP and H446/DDP) were transfected with related vectors and subjected to cisplatin, autophagy inhibitor, activator, or extracellular signal–regulated kinase (ERK) activator. Flow cytometry, CCK8 and colony formation assays were performed for testing apoptosis and cell viability. The related RNAs or proteins were detected by qRT-PCR or Western blot. Chromatin immunoprecipitation, luciferase reporter assay or RNA immunoprecipitation were used for validating the interaction between miR-152-3p and ELF1 or NCAM1. Co-IP verified the binding between NCAM1 and ERK. The role of miR-152-3p in cisplatin resistance of NSCLC was also validated in vivo. The results showed that miR-152-3p and ELF1 were decreased in NSCLC tissues. miR-152-3p reversed cisplatin resistance by inhibiting autophagy through NCAM1. NCAM1 promoted autophagy through the ERK pathway and facilitated cisplatin resistance. ELF1 positively regulated miR-152-3p level by directly interacting with miR-152-3p promoter. miR-152-3p targeted NCAM1 to regulate NCAM1 level and then affected the binding of NCAM1 to ERK1/2. ELF1 inhibited autophagy and reversed cisplatin resistance through miR-152-3p/NCAM1. miR-152-3p inhibited autophagy and cisplatin resistance of xenograft tumor in mice. In conclusion, our study revealed that ELF1 inhibited autophagy to attenuate cisplatin resistance through the miR-152-3p/NCAM1/ERK pathway in H446/DDP and A549/DDP cells, suggesting a potential novel treatment strategy for NSCLC.