慢病毒亚急性海绵状脑病—2例临床病理报告

亚急性海绵状脑病(简称CJD)是非常规慢病毒惑染的进行性中枢神经系统广泛受累的疾病。临床特点是进行性意识障碍、痴呆、肌阵挛发怍、肌强直、锥体束、锥体外束和小脑损害等体征。病理特点是不同程度的海绵状改变、神经细胞脱失和星形细胞增生等。Gibbs等首次用CJD病人脑组织接种黑猩猩脑内发病,以后相继在灵长类和非灵长类动物接种发病,病理改变与人类CJD相似,但人类自然传染方式仍不清。本病发病率在北美及其它西方国家约1/1000000/年,我国近年来亦有个案报道,

论体育对现代人心理健康的影响

普遍增强全民体质,改善和提高全民族的健康水平是我国体育的根本目的。人的健康应该是生理和心理健康的结合,二者缺一不可。

论民族体育在开发民族地区人材资源中的作用

论民族体育在开发民族地区人材资源中的作用中南民族学院卢斌人材资源的开发，主要还是依靠教育。如何根据民族地区的现实条件办好教育，更多更快、更好地培养德、智、体全面发展的社会主义建设者和接班人，是民族地区人材资源开发的最关键的环节；而充分利用民族体育深受...

5-HT回收阻断剂治疗强迫症的研究进展(综述)

过去专业界一直认为强迫症系心因性疾患,属于心理神经症(Psychoneuroses)范畴。自从5-HT回收阻断剂氯丙咪嗪治疗强迫症获效后,近几年来国内外相继使用这类药物治疗强迫症取得了可喜的成果。本文综述了常用的5-HT回收阻断剂氮丙咪嗪、氟西订、氟伏草胺、丁螺环铜,抗强迫治疗的一些研究进展。一、作用机制研究 5-HT回收阻断剂通过阻断5-HT的回收(再摄取)

试论体育对智育发展的影响

在我国,人们对于体育运动在促进智育发展中所起的重要作用,一直没有引起足够的重视。殊不知,通过体育教学与体育锻炼,在增强学生体质的同时,能使儿童和青少年的神经系统特别是大脑得到充分的发育,从而改善神经系统特别是大脑的结构和功能。而神经系统特别是大脑的结构和机能,直接关系着人们的智力活动与学习效能。

rSac3, a novel Sac domain phosphoinositide phosphatase, promotes neurite outgrowth in PC12 cells

Sac domain-containing proteins belong to a newly identified family of phosphoinositide phosphatases （the PIPPase family）. Despite well-characterized enzymatic activity, the biological functions of this mammalian Sac domain PIPPase family remain largely unknown. We identified a novel Sac domain-containing protein, rat Sac3 （rSac3）, which is widely expressed in various tissues and localized to the endoplasmic reticulum, Golgi complex and recycling endosomes, rSac3 displays PIPPase activity with PI（3）P, PI（4）P and PI（3,5）P2 as substrates in vitro, and a mutation in the catalytic core of the Sac domain abolishes its enzymatic activity. The expression of rSac3 is upregulated during nerve growth factor （NGF）-stimulated PC 12 cell neuronal differentiation, and overexpression of this protein promotes neurite outgrowth in PC 12 cells. Conversely, inhibition ofrSac3 expression by antisense oligonucleotides reduces neurite outgrowth of NGF- stimulated PC 12 cells, and the active site mutation of rSac3 eliminates its neurite-outgrowth-promoting activity. These results indicate that rSac3 promotes neurite outgrowth in differentiating neurons through its PIPPase activity, suggesting that Sac domain PIPPase proteins may participate in forward membrane trafficking from the endoplasmic reticulum and Golgi complex to the plasma membrane, and may function as regulators of this crucial process of neuronal cell growth and differentiation.

Research advancements of axonal remyelination in spinal cord injury

Spinal cord injuries(SCI)usually result in impairment of axonal conduction and sensorimotor function.There are no effective therapy to completely repair SCI.Axonal demyelination is very common as a pathologic change in SCI,and demyelination partly contributes to neural function impairment.So,it may be reasonable that remyelination of demyelinated axons become one of effective therapeutic targets for SCI treatment. Demyelination involves myelin breakdown and loss of myelin-forming cells(oligodendrocytes).The death of oligodendrocytes plays a key role in axonal demyelination in SCI.Recently a number of studies demonstrate that cell replacements could facilitate axonal remyelination and restore axonal conductive func- tion.Thus,it is expected that myelinogenetic cell transplantation(oligodendroglial lineage)will have good prospect as an effective therapy to improve axonal remyelination and restore neural function for SCI treat- ment in the near future.

Polyglutamine toxicity in non-neuronal cells

The neurodegenerative polyglutamine diseases are caused various disease proteins. Although these mutant proteins are by an expansion of unstable polyglutamine repeats in expressed ubiquitously in neuronal and non-neuronal cells, they cause selective degeneration of specific neuronal populations. Recently, increasing evidence shows that polyglutamine disease proteins also affect non-neuronal cells. However, it remains unclear how the expression of polyglutamine proteins in non-neuronal cells contributes to the course of the polyglutamine diseases. Here, we discuss recent findings about the expression of mutant polyglutamine proteins in non-neuronal cells and their influence on neurological symptoms. Understanding the contribution of non-neuronal polyglutamine proteins to disease progres- sion will help elucidate disease mechanisms and also help in the development of new treatment options.

PAd-shRNA-PTN reduces pleiotrophin of pancreatic cancer cells and inhibits neurite outgrowth of DRG

AIM:To investigate the silencing effects of pAdshRNA-pleiotrophin(PTN) on PTN in pancreatic cancer cells,and to observe the inhibition of pAd-shRNA-PTN on neurite outgrowth from dorsal root ganglion(DRG) neurons in vitro.METHODS:PAd-shRNA-PTN was used to infect pancreatic cancer BxPC-3 cells;assays were conducted for knockdown of the PTN gene on the 0th,1st,3rd,5th,7th and 9th d after infection using immunocytochemistry,real-time quantitative polymerase chain reaction(PCR),and Western blotting analysis.The morphologic changes of cultured DRG neurons were observed by mono-culture of DRG neurons and co-culture with BXPC-3 cells in vitro.RESULTS:The real-time quantitative PCR showed that the inhibition rates of PTN mRNA expression in the BxPC-3 cells were 20%,80%,50% and 25% on the 1st,3rd,5th and 7th d after infection.Immunocytochemistry and Western blotting analysis also revealed the same tendency.In contrast to the control,the DRG neurons co-cultured with the infected BxPC-3 cells shrunk;the number and length of neurites were significantly decreased.CONCLUSION:Efficient and specific knockdown of PTN in pancreatic cancer cells and the reduction in PTN expression resulted in the inhibition of neurite outgrowth from DRG neurons.

A retrograde apoptotic signal originating in NGF-deprived distal axons of rat sympathetic neurons in compartmented cultures

Previous investigations of retrograde survival signaling by nerve growth factor （NGF） and other neurotrophins have supported diverse mechanisms, but all proposed mechanisms have in common the generation of survival signals retrogradely transmitted to the neuronal cell bodies. We report the finding of a retrograde apoptotic signal in axons that is suppressed by local NGF signaling. NGF withdrawal from distal axons alone was sufficient to activate the pro-apoptotic transcription factor, c-jun, in the cell bodies. Providing NGF directly to cell bodies, thereby restoring a source of NGF-induced survival signals, could not prevent c-jun activation caused by NGF withdrawal from the distal axons. This is evidence that c-jun is not activated due to loss of survival signals at the cell bodies. Moreover, blocking axonal transport with colchicine inhibited c-jun activation caused by NGF deprivation suggesting that a retrogradely transported pro-apoptotic signal, rather than loss of a retrogradely transported survival signal, caused c-jun activation. Additional experiments showed that activation of c-jun, pro-caspase-3 cleavage, and apoptosis were blocked by the protein kinase C inhibitors, rottlerin and chelerythrine, only when applied to distal axons suggesting that they block the axon-specific pro-apoptotic signal. The rottlerin-sensitive mechanism was found to regulate glyco- gen synthase kinase 3 （GSK3） activity. The effect of siRNA knockdown, and pharmacological inhibition of GSK3 suggests that GSK3 is required for apoptosis caused by NGF deprivation and may function as a retrograde carrier of the axon apoptotic signal. The existence of a retrograde death signaling system in axons that is suppressed by neurotro- phins has broad implications for neurodevelopment and for discovering treatments for neurodegenerative diseases and neurotrauma.

Dendritic cell therapy with improved outcome in glioma multiforme―a case report

Malignant gliomas are the most devastating tumors in clinical practice and nave poorest survival, Immunological treatment of such patients may likely increase the survival and quality of life. Dendritic cells （DCs）, most potent antigen presenting cells in combination with oral chemotherapeutic agents may be tried for patients giving consent to such treatment. We have successfully combined the two therapies in an adult male patient who was on downhill course after being operated on once with post operation chemotherapy and radiotherapy for glioma in the left parietal area. He received five dendritic cell therapy vaccines in combination with oral chemotherapy and responded dramatically having near normal quality of life for an additional five months with this regime, increasing the survival after operation to 11 months. This therapy is continuing with radiological betterment of the lesion. The DCs are matured with antigen extracted from wax embedded tissue at 6th day of culture. We feel that the treatment can be given to more number of patients to establish its efficacy for the dreaded cancer glioblastoma multiforme.

Does Muller Cell Differentiation Occur Prior to the Emergence of Synapses in Embryonic Turtle Retina？

MOiler cells are the main glial cells in the retina, and are related to plexiform layer activity. Recent studies have demonstrated that Muller cells are involved in the synaptic conservation, plasticity, development and metabolism of glutamate. During turtle retinal development, layers, cells and synapses appear at different times. The aim of this research is to study the emergence of Muller cells during embryonic development and their relationship with the synaptogenesis. The authors used retinas from Trachemys scripta elegans embryos at stages S14, 18, 20, 23, and 26. Some retinas were processed with immunocytochemistry in order to detect the presence of glutamine synthetase in Muller cells, which was used as a marker of these ceils. Other retinas from the same stages were processed for ultrastructural studies. Samples were observed in confocal and transmission electron microscopes, respectively. The present results show that glutamine synthetase expression in MOiler cells occurs at S18, before the emergence of the retinal layers and the early synapses.

Axonal microRNAs： localization, function and regulatory mechanism during axon development

Subcellular localization and translation of messenger RNAs are essential for the regulation of neuronal development and synaptic function. As post-transcriptional regulators, microRNAs （miRNAs） have been emerging as central players in the development and maturation of the nervous system. Recent discoveries reveal the critical functions of miRNAs in the axon of neurons via multiple pathways of molecular regulation. Here, we introduce methods for isolating axonal miRNAs and review recent findings on the localization and function as well as regulatory mechanism of axonal miRNAs during axon development.

Coculture of elongated neuron axon with poly (D,L-lactide-co-glycolide) biomembrane in vitro

Objective: To elongate human nerve axon in cultu re and search for suitable support matrices for peripheral nervous system trans plantation. Methods: Human embryo cortical neuronal cells,seeded on poly ( D,L-lactide-co-glycolide) (PLGA) membrane scaffolds,were elongated with a se lf-made neuro-axon extending device. The growth and morphological changes of n euron axons were observed to measure axolemmal permeability after elongation. Ne urofilament protein was stained by immunohistochemical technique.Results: Human embryo neuron axon could be elongated and cultur ed on the PLGA membrane and retain their normal form and function. Conclusions: Three dimensional scaffolds with elongated neuron axon have the basic characteristics of artificial nerves,indicating a fundement al theory of nerve repair with elongated neuron axon.

Bulk endocytosis at neuronal synapses

Neurotransmitter-containing synaptic vesicle(SV)fusion with the nerve terminal plasma membrane initiates neurotransmission in response to neuronal excitation.Under mild stimulation,the fused vesicular membrane is retrieved via kiss-and-run and/or clathrin-mediated endocytosis,which is sufficient to maintain recycling of SVs.When neurons are challenged with very high stimulation,the number of fused SVs can be extremely high,resulting in significant plasma membrane addition.Under such conditions,a higher capacity retrieval pathway,bulk endocytosis,is activated to redress this large membrane imbalance.Despite first being described more than 40 years ago,the molecular mechanisms underpinning this important process have yet to be clearly defined.In this review,we highlight the current evidence for bulk endocytosis and its prevalence in various neuronal models,as well as discuss the underlying molecular components.

Control of demyelination for recovery of spinal cord injury

Since loss of oligodendrocytes and consequent demyelination of spared axons severely impair the functional recovery of injured spinal cord, it is reasonably expected that the reduction of oligodendroglial death and enhanced remyelination of demyelinated axons will have a therapeutic potential to treat spinal cord injury. Amelioration of axonal myelination in the injured spinal cord is valuable for recovery of the neural function of incompletely injured patients. Here, this article presents an overview about the patho-physiology and mechanism of axonal demyelination in spinal cord injury and discusses its therapeutic significance in the treatment of spinal cord injury. Moreover, it further introduces the recent strategies to improve the axonal myeliantion to facilitate functional recovery of spinal cord injury.

Influence of cryopreserved olfactory ensheathing cells transplantation on axonal regeneration in spinal cord of adult rats

Objective: To observe the effects of cryopreserved olfactory ensheathing cells (OECs) transplantation on axonal regeneration and functional recovery following spinal cord injury in adult rats. Methods: Twenty-four rats were divided into experimental and control groups, each group having 12 rats. The spinal cord injury was established by transecting the spinal cord at T 10 level with microsurgery scissors. OECs were purified from SD rat olfactory bulb and cultured in DMEM (Dulbeccos minimum essential medium) and cryopreserved (-120℃) for two weeks. OECs suspension [(1-1.4)×10 5/ul] was transplanted into transected spinal cord, while the DMEM solution was injected instead in the control group. At 6 and 12 weeks after transplantation, the rats were evaluated with climbing test and MEP (moter evoked potentials) monitoring. The samples of spinal cord were procured and studied with histological and immunohisto chemical stainings. Results: At 6 weeks after transplantation, all of the rats in both transplanted and control groups were paraplegic, and MEPs could not be recorded. Morphology of transplanted OECs was normal, and OECs were interfused with host well. Axons could regrow into gap tissue between the spinal cords. Both OECs and regrown axons were immunoreactive for MBP. No regrown axons were found in the control group. At 12 weeks after transplantation, 2 rats (2/7) had lower extremities muscle contraction, 2 rats (2/7) had hip and/or knee active movement, and MEP of 5 rats (5/7) could be recorded in the calf in the transplantation group. None of the rats (7/7) in the control group had functional improvement, and none had MEPs recorded. In the transplanted group, histological and immunohistochemical methods showed the number of transplanted OECs reduced and some regrown axons had reached the end of transected spinal cord. However, no regrown axons could be seen except scar formation in the control group. Conclusions: Cryopreserved OECs could integrated with the host and promote regrowing axons across the transected spinal cord ends.

Experimental study on the apoptosis of the astrocytes and the oligodendrocytes induced by Ca^(2+) reperfusion

Objective: To investigate the apoptosis rules of the astrocytes and oligodendrocytes induced by Ca 2+ reperfusion. Methods: The apoptosis of purified cultured astrocytes and oligodendrocytes induced by Ca 2+ reperfusion and the relationship between the development of the cell apoptosis and post-reperfusion time was observed. Results: Both the astrocytes and oligodendrocytes were obviously in a time-dependent fashion, and the apoptosis ratios of the oligodendrocytes ( 39.73%± 4.16%) were higher than the astrocytes ( 19.64%± 4.67%) 24 hours after Ca 2+ reperfusion. The TUNEL positive cells were 13.6± 1.82 and 21.4± 1.95 at every visual field of astrocytes and oligodendrocytes respectively 24 hours after Ca 2+ reperfusion. Conclusions: The astrocytes and oligodendrocytes are similar with the development rules on apoptosis and have different susceptiveness to the situation.

Foxn4:A multi-faceted transcriptional regulator of cell fates in vertebrate development

Vertebrate development culminates in the generation of proper proportions of a large variety of different cell types and subtypes essential for tissue,organ and system functions in the right place at the right time.Foxn4,a member of the forkhead box/winged-helix transcription factor superfamily,is expressed in mitotic progenitors and/or postmitotic precursors in both neural(e.g.,retina and spinal cord)and non-neural tissues(e.g.,atrioventricular canal and proximal airway).During development of the central nervous system,Foxn4 is required to specify the amacrine and horizontal cell fates from multipotent retinal progenitors while suppressing the alternative photoreceptor cell fates through activating Dll4-Notch signaling.Moreover,it activates Dll4-Notch signaling to drive commitment of p2 progenitors to the V2b and V2c interneuron fates during spinal cord neurogenesis.In development of non-neural tissues,Foxn4 plays an essential role in the specification of the atrioventricular canal and is indirectly required for patterning the distal airway during lung development.In this review,we highlight current understanding of the structure,expression and developmental functions of Foxn4 with an emphasis on its cell-autonomous and non-cell-autonomous roles in different tissues and animal model systems.