Mitotic phosphorylation of PRC1 at Thr470 is required for PRC1 oligomerization and proper central spindle organization

在细胞分裂期间，染色体分离被和着丝点的锭子微导管的相互作用安排。进在分开的染色单体之间的一支组织中央锭子的 interpolarmicrotubules 的戏剧的改变为胞质分裂的开始和实行被要求。中央锭子组织要求有丝分裂的 kinesins， chromosomal 旅客蛋白质建筑群，和微导管捆绑蛋白质 PRC1。由在 Thr470 和 Thr481 的 Cdc2 的 PRC1 isphosphorylated 在有丝分裂期间。然而，在 Thr470 的功能的关联 ofPRC1 磷酸化留下了逃犯。这里，我们证明 thenon-phosphorylatable 异种 PRC1 (T470A ) 然而并非 phospho-mimicking 异种 PRC1 (T470E ) 的那表情引起中央锭子的异常组织。Immunoprecipitation 实验与野类型的 PRC1 显示那 bothPRC1 (T470A ) 和 PRC1 (T470E ) 突变蛋白质伙伴，建议 Thr470 的 thatphosphorylation 不改变 PRC1 自我协会。另外，在 vitroco 沉积，实验证明 PRC1 绑在独立于 Thr470 的 phosphorylationstate 的微导管。胶化过滤实验建议了 PRC1 的 Thr470 promotesoligomerization 的那磷酸化。给 Thr470 磷酸化的那预防禁止 PRC1oligomerization 试管内并且引起中央锭子体内的一个异常组织的事实，我们建议这 phosphorylation 依赖的 PRC1 oligomerization 保证中央锭子汇编在房间周期发生在适当时间。

Degenerative alterations in noradrenergic neurons of the locus coeruleus in Alzheimer's disease

Mice carrying mutant amyloid precursor protein and presenilin-1 genes （APP/PS1 double trans- genic mice） have frequently been used in studies of Alzheimer＇s disease; however, such studies have focused mainly on hippocampal and cortical changes. The severity of Alzheimer＇s disease is known to correlate with the amount of amyloid-13 protein deposition and the number of dead neurons in the locus coeruleus. In the present study, we assigned APP/PS1 double transgenic mice to two groups according to age： young mice （5-6 months old） and aged mice （16-17 months old）. Age-matched wild-type mice were used as controls. Immunohistochemistry for tyrosine hydroxylase （a marker of catecholaminergic neurons in the locus coeruleus） revealed that APP/PS1 mice had 23% fewer cells in the locus coeruleus compared with aged wild-type mice. APP/PS1 mice also had increased numbers of cell bodies of neurons positive for tyrosine hydroxylase, but fewer tyrosine hydroxylase-positive fibers, which were also short, thick and broken. Quantitative analysis using unbiased stereology showed a significant age-related increase in the mean volume of tyrosine hy- droxylase-positive neurons in aged APP/PS1 mice compared with young APP/PS1 mice. Moreover, the mean volume of tyrosine hydroxylase-positive neurons was positively correlated with the total volume of the locus coeruleus. These findings indicate that noradrenergic neurons and fibers in the locus coeruleus are predisposed to degenerative alterations in APP/PS1 double transgenic mice.

Selective neuronal PTEN deletion：can we take the brakes off of growth without losing control？

The limited ability for injured adult axons to regenerate is a major cause for limited functional recovery after injury to the nervous system,motivating numerous efforts to uncover mechanisms capable of enhancing regeneration potential.One promising strategy involves deletion or knockdown of the phosphatase and tensin（PTEN） gene.Conditional genetic deletion of PTEN before,immediately following,or several months after spinal cord injury enables neurons of the corticospinal tract（CST） to regenerate their axons across the lesion,which is accompanied by enhanced recovery of skilled voluntary motor functions mediated by the CST.Although conditional genetic deletion or knockdown of PTEN in neurons enables axon regeneration,PTEN is a well-known tumor suppressor and mutations of the PTEN gene disrupt brain development leading to neurological abnormalities including macrocephaly,seizures,and early mortality.The long-term consequences of manipulating PTEN in the adult nervous system,as would be done for therapeutic intervention after injury,are only now being explored.Here,we summarize evidence indicating that long-term deletion of PTEN in mature neurons does not cause evident pathology; indeed,cortical neurons that have lived without PTEN for over 1 year appear robust and healthy.Studies to date provide only a first look at potential negative consequences of PTEN deletion or knockdown,but the absence of any detectable neuropathology supports guarded optimism that interventions to enable axon regeneration after injury are achievable.

Endogenous bioelectric fields: a putative regulator of wound repair and regeneration in the central nervous system

Studies on a variety of highly regenerative tissues, including the central nervous system（CNS） in non-mammalian vertebrates, have consistently demonstrated that tissue damage induces the formation of an ionic current at the site of injury. These injury currents generate electric fields（EF） that are 100-fold increased in intensity over that measured for uninjured tissue. In vitro and in vivo experiments have convincingly demonstrated that these electric fields（by their orientation, intensity and duration） can drive the migration, proliferation and differentiation of a host of cell types. These cellular behaviors are all necessary to facilitate regeneration as blocking these EFs at the site of injury inhibits tissue repair while enhancing their intensity promotes repair. Consequently, injury-induced currents, and the EFs they produce, represent a potent and crucial signal to drive tissue regeneration and repair. In this review, we will discuss how injury currents are generated, how cells detect these currents and what cellular responses they can induce. Additionally, we will describe the growing evidence suggesting that EFs play a key role in regulating the cellular response to injury and may be a therapeutic target for inducing regeneration in the mammalian CNS.

Expression of vimentin and glial fibrillary acidic protein in central nervous system development of rats

Objective: To investigate the distribution and contents of vimentin(Vim) and glial fibrillary acidic protein(GFAP) immunoreactivities in the central nervous system(CNS)of normal newborn, adult and aged rats.Methods: In this study, thirty healthy and normal Sprague–Dawley rats were simply classified into three groups: Newborn(7 days aged), adult(5 months aged) and aged(24 months aged) rats. Brains and spinal cord were dissected and cut into frozen sections. The expression of Vim and GFAP in CNS were detected by confocal immunofluorescence.Results: In each group, Vim was expressed in all the regions of CNS including the hippocampal, cerebral cortex, the third ventricle and spinal cord, and the expression was highest in neuron-like cell of newborn rats, while Vim was mainly expressed in cell bodies in adult and aged rats. GFAP was expressed in all the regions of CNS including the hippocampal, cerebral cortex, the third ventricle and spinal cord, and the expression was in astrocytes of aged rats. In the third ventricle, Vim was detected in all groups, and only observed in neuron-like cells of newborn. Meanwhile, the GFAP expression showed no significant differences between adult and aged rats in this region. The co-localization of Vim and GFAP were mainly observed in hippocampus and cerebral cortex of newborn,but this co-localization was found in the third ventricle of the rats in all groups.Conclusion: Our data demonstrate for the first time that the expression of Vim and GFAP in the rat's CNS during development. This data may provide a foundation for the further mechanistic studies of these two main intermediate filaments during development of CNS.

TrkB and p-trkB expression in brain-derived neurotrophic factor-pretreated rat retina following acute high intraocular pressure

BACKGROUND： Exogenous brain-derived neurotrophic factor （BDNF） promotes retinal ganglion cell survival. However, the protective mechanisms remain unclear. OBJECTIVE： To investigate changes in retinal tyrosine kinase receptor B （trkB） expression and effects of exogenous BDNF on trkB activation in a rat model of acute high intraocular pressure （HtOP）. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Department of Anatomy and Neurobiology, Xiangya Medical School, Central South University from January 2004 to August 2006. MATERIALS： Rabbit anti-BDNF and anti-trkB.FL（full-length） polyclonal antibodies were purchased from Santa Cruz Biotechnology, USA; rabbit anti-p-trkB polyclonal antibodies were purchased from Cellsignal, USA. METHODS： A total of 48 healthy, adult, Sprague Dawiey rats were randomly assigned to acute HIOP （without BDNF pre-treatment） and BDNF pre-treated groups, with 24 animals in each group. In the BDNF pre-treated group, the left eyes were intravitreally injected with 3 pg/kg BDNF 2 days prior to HIOP. Rats in the acute HIOP group were not pre-treated with BDNE HIOP models were established by increased intraocular pressure in the left eyes until the b-wave of flash electroretinogragh disappeared and pressure was maintained for 60 minutes. The right eyes of all rats were not treated and served as the normal controls. MAIN OUTCOME MEASURES： Retinal structure and cell numbers in the ganglion cell layer （GCL） were detected by Nissl staining; expression of trkB and phosphorylated trkB in the rat retina were determined by immunohistochemistry. RESULTS： A greater number of GCL neurons were observed in the pre-treated group compared to the acute HIOP group （P 〈 0.05）. TrkB expression was significantly increased following HIOP at days 1 and 3 （P 〈 0.05）, but expression varied between retinal areas. Although trkB expression decreased at 7 days, phosphorylated trkB dramatically decreased with increasing time （P 〈 0.05）. TrkB expression in BDNF pre-treated rats was similar to the acute HIOP group at early injury time points. Nevertheless, trkB expression was significantly decreased compared to the acute HIOP group at 7 days （P 〈 0.05）, and phosphorylated trkB expression was significantly greater compared to the acute HIOP group at each time point （P〈 0.05）. CONCLUSION： TrkB expression displayed temporal and spatial changes in the rat retina following acute HIOP, and trkB up-regulation suggested that more BDNF was required for treating the injured retina. Exogenous BDNF partially ameliorated decreased expression of phosphorylated trkB and provided protection to the injured retina, to a certain degree, following HIOP.