The p75 neurotrophin receptor is expressed by adult mouse dentate progenitor cells and regulates neuronal and non-neuronal cell genesis

Background  

The ability to regulate neurogenesis in the adult dentate gyrus will require further identification and characterization of the receptors regulating this process. In vitro and in vivo studies have demonstrated that neurotrophins and the p75 neurotrophin receptor (p75^NTR) can promote neurogenesis; therefore we tested the hypothesis that p75^NTR is expressed by adult dentate gyrus progenitor cells and is required for their proliferation and differentiation.     

Cerebrospinal fluid promotes survival and astroglial differentiation of adult human neural progenitor cells but inhibits proliferation and neuronal differentiation

Background  

Neural stem cells (NSCs) are a promising source for cell replacement therapies for neurological diseases. Growing evidence suggests an important role of cerebrospinal fluid (CSF) not only on neuroectodermal cells during brain development but also on the survival, proliferation and fate specification of NSCs in the adult brain. Existing in vitro studies focused on embryonic cell lines and embryonic CSF. We therefore studied the effects of adult human leptomeningeal CSF on the behaviour of adult human NSCs (ahNSCs).     

Anatomy and cell biology of the laryngeal motor neurons: Implications for the treatment of spasmodic dysphonia

Changes in neuroanatomical pathways in the central nervous system presumably play key roles in the pathogenetic mechanism underlying spasmodic dysphonia. However, practical considerations of accessibility to clinical intervention have focused efforts on treatments based on manipulations of laryngeal motor neurons, the most peripheral extent of these pathways. This review discusses aspects of the anatomy and cell biology of the laryngeal motor neurons, which provide a basis for the understanding of current techniques for the treatment of this disorder. In addition, consideration is given to the significance of unusual morphological characteristics of the laryngeal motor neurons and to cellular processes, which may ultimately offer potential for more selective clinical strategies.     

The role of the cytoskeleton in cell body enlargement,increased nuclear eccentricity and chromatolysis in axotomized spinal motor neurons

Background  

When spinal motor axons are injured, the nucleolus, nucleus and cell body of the injured cell transiently increase in size, the nucleus becomes more eccentrically placed, and the organization of polyribosomes into Nissl bodies is temporarily disrupted. The mechanisms for these classical morphological responses to axotomy have not been satisfactorily explained.     

Treatment of trigeminal ganglion neurons in vitro with NGF,GDNF or BDNF: effects on neuronal survival,neurochemical properties and TRPV1-mediated neuropeptide secretion

Background  

Nerve growth factor (NGF), glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) all play important roles in the development of the peripheral sensory nervous system. Additionally, these growth factors are proposed to modulate the properties of the sensory system in the adult under pathological conditions brought about by nerve injury or inflammation. We have examined the effects of NGF, GDNF and BDNF on adult rat trigeminal ganglion (TG) neurons in culture to gain a better understanding of how these growth factors alter the cytochemical and functional phenotype of these neurons, with special attention to properties associated with nociception.     

Proliferative reactive gliosis is compatible with glial metabolic support and neuronal function

Background

Trail-making tests, such as the Concept Shifting Task (CST), can be used to test the effects of treatment on cognitive performance over time in various neuropsychological disorders. However, cognitive performance in such experimental designs might improve as a result of the practice obtained during repeated testing rather than the treatment itself. The current study investigated if practice affects the accuracy and duration of performance on the repeatedly administered Concept Shifting Task modified to make it resistant to practice (mCST). The mCST was administered to 54 healthy participants twice a day, before and after a short break, for eight days. Results. The ANOVA and meta-analysis showed that there was no improvement in the mCST accuracy on the last vs. the first trial (Hedges' g = .14, p = .221) or within the session (after vs. before the break on all days; g = .01, p = .922). However, the participants performed the task faster on the last vs. the first trial (g = -.75, p < .001) and after vs. before the break on all days (g = -.12, p = .002). Conclusions. Repeated administration of the mCST does not affect the accuracy of performance on the test. However, practice might contribute to faster performance on the mCST over time and within each session.     

Non-receptor tyrosine kinase Src is required for ischemia-stimulated neuronal cell proliferation via Raf/ERK/CREB activation in the dentate gyrus

Background  

Neurogenesis in the adult mammalian hippocampus may contribute to repairing the brain after injury. However, Molecular mechanisms that regulate neuronal cell proliferation in the dentate gyrus (DG) following ischemic stroke insult are poorly understood. This study was designed to investigate the potential regulatory capacity of non-receptor tyrosine kinase Src on ischemia-stimulated cell proliferation in the adult DG and its underlying mechanism.     

A primary model of decoherence in neuronal microtubules based on the interaction Hamiltonian between microtubules and plasmon in neurons

Microtubules(MTs) are part of the cellular cytoskeleton and they play a role in many activities, such as cell division and maintenance of cell shape. In recent years, MTs have been thought to be involved in storing and processing information.Several models have been developed to describe the information-processing ability of MTs. In these models, MTs are considered as a device that can transmit quantum information. However, MTs are affected by the "wet and warm" cellular environment, thus it is essential to calculate the decoherence time. Many researchers have attempted to calculate this parameter but the values that have been obtained vary markedly. Previous studies considered the cellular environment as a distant ion; however, this treatment is somewhat simplified. In this study, we develop a model to determine the decoherence time in neuronal MTs while considering the interaction effects of the neuronal fluid environment. The neuronal environment is considered as a plasmon reservoir. The coupling between MTs and neuronal environment occurs due to the interaction between dipoles and plasmon. The interaction Hamiltonian is derived by using the second quantization method, and the coupling coefficient is calculated. Finally, the decoherence time scale is estimated according to the interaction Hamiltonian.In this paper, the time scale of decoherence in MTs is approximately 1 fs-100 fs. This model may be used as a reference in other decoherence processes in biological tissues.     

CTLA-4 blockade during dendritic cell based booster vaccination influences dendritic cell survival and CTL expansion

Dendritic cells (DCs) are potent antigen-presenting cells and critical for the priming of CD8+ T cells. Therefore the use of these cells as adjuvant cells has been tested in a large number of experimental and clinical vaccination studies, in particular cancer vaccine studies. A number of protocols are emerging that combine vaccination with CTL expanding strategies, such as e.g. blockade of CTLA-4 signalling. On the other hand, the lifespan and in vivo survival of therapeutic DCs have only been addressed in a few studies, although this is of importance for the kinetics of CTL induction during vaccination. We have previously reported that DCs loaded with specific antigens are eliminated by antigen specific CTLs in vivo and that this elimination affects the potential for in vivo CTL generation. We now show that CTLA-4 blockade increases the number of DC vaccine induced LCMV gp33 specific CTLs and the lysis of relevant in vivo targets. However, the CTLA-4 blockage dependent expansion of CTLs also affect DC survival during booster DC injections and our data suggest that during a booster DC vaccine, the largest increase in CTL levels is already obtained during the first vaccination.     

Midkine,heparin-binding growth factor,blocks kainic acid-induced seizure and neuronal cell death in mouse hippocampus

Background  

Midkine (MK), a member of the heparin-binding growth factor family, which includes MK and pleiotrophin, is known to possess neurotrophic and neuroprotective properties in the central nervous system. Previous studies have shown that MK is an effective neuroprotective agent in reducing retinal degeneration caused by excessive light and decreasing hippocampal neuronal death in ischemic gerbil brain. The present study was undertaken to investigate whether MK acts as an anticonvulsant in kainic acid (KA)-induced seizure in mouse and blocks KA-mediated neuronal cell death in hippocampus.     

Spatial distribution of AT- and GC-rich DNA within interphase cell nuclei of Triatoma infestans Klug

Heterochromatin bodies in single- and multichromocentered interphase cell nuclei of Triatoma infestans, a vector of Chagas disease, have been suggested to contain AT-rich DNA, based on their positive response to Q-banding and Hoechst 33248 treatment. No information exists on whether GC-rich DNA is also present in these nuclei and whether it plays a role on chromatin condensation. Considering that methodologies more precise than those previously used to determine DNA base composition in situ are currently available, and that the spatial distribution of chromatin areas differing in composition in interphase cell nuclei of different species is a matter of interest, the localization of AT- and GC-rich DNA in T. infestans nuclei is revisited here. The methodologies used included DAPI/AMD and CMA(3)/Distamycin differential staining, Feulgen-DNA image analysis following Msp I and Hpa II enzymatic digestion, 5-methylcytidine immunodetection, AgNOR response, confocal microscopy, and the 5-aza-2'-deoxycytidine (5-AZA) demethylation assay. The results identified the presence of AT-rich/GC-poor DNA in chromocenters and evenly distributed AT and GC sequences in euchromatin. A GC-rich DNA zone encircling the chromocenters was also found but it could not be associated with NOR regions. To corroborate the DNA AT-richness in T. infestans nuclei, bioinformatic analyses were also performed. Methylated cytosine was evident at some points of the chromocenters' edge in single- and multichromocentered nuclei and at the euchromatin of multichromocentered nuclei and could be transiently affected by the 5-AZA treatment. The present results suggest that in the particular case of chromocenters of the hemipteran T. infestans, cytosine methylation is not a relevant factor involved in chromatin condensation.     

固体氧化物燃料电池模式阳极内传输与电化学反应耦合机理

模式电极因其结构可控、电化学/化学反应活性位和物质传输路径明确等优势,被广泛应用于固体氧化物燃料电池新型电极研究.现有研究多采用模式电极研究新材料电化学特性、表界面催化反应机理等,尚未涉及几何结构对其内部传输与电化学反应耦合机理的影响,限制了模式电极的应用.本文建立了固体氧化物燃料电池阳极内电荷传输与电化学反应过程的格子玻尔兹曼模拟方法,明确了控制电极过程的关键无量纲参数及其对电极性能的影响规律,研究了模式阳极几何结构的影响机理.根据电极性能对无量纲参数的敏感程度,绘制了指导模式阳极设计与运行的相图,指出相图过渡区(电极性能随操作参数显著变化区域)为进行反应机理研究的最佳操作参数取值范围.同时,研究发现模式阳极电子导体内电子的快速迁移虽不限制阳极性能,其几何结构显著影响过渡区范围;离子导体内离子迁移为影响阳极性能的限速步骤,但其几何结构几乎不影响过渡区范围.本文的数值方法与机理研究结果可为固体氧化物燃料电池模式电极的设计提供重要理论依据.     

Membrane trafficking and mitochondrial abnormalities precede subunit c deposition in a cerebellar cell model of juvenile neuronal ceroid lipofuscinosis

Background  

JNCL is a recessively inherited, childhood-onset neurodegenerative disease most-commonly caused by a ~1 kb CLN3 mutation. The resulting loss of battenin activity leads to deposition of mitochondrial ATP synthase, subunit c and a specific loss of CNS neurons. We previously generated Cln3 ^Δex7/8 knock-in mice, which replicate the common JNCL mutation, express mutant battenin and display JNCL-like pathology.     

In vitro evaluation of vascular endothelial and smooth muscle cell survival and apoptosis in response to hypothermia and freezing

The success of endovascular techniques such as balloon angioplasty and stenting in the treatment of atherosclerotic vascular disease has been limited by an aggressive proliferative response leading to neointimal hyperplasia and re-stenosis. A new endovascular therapy combining cold treatment with balloon dilation has been proposed to prevent arterial re-stenosis. In order to evaluate the potential of this application, studies were conducted investigating the effects of hypothermia and freezing on human arteries at the cellular level. Cultured arterial endothelial cells and smooth muscle cells were chilled or frozen under controlled thermal conditions. The viability response of the cells was measured with a variety of assays quantifying necrosis, apoptosis, and cell proliferation. These data establish correlations between thermal conditions and the extent and nature of arterial freezing injury. Arterial smooth muscle cells were found to be susceptible to freeze-induced apoptosis in a temperature range of -5 to -15 degrees C. Endovascular cryotherapy designed to induce apoptosis in arterial smooth muscle cells may limit neointimal formation and thereby improve the durability of conventional angioplasty.     

The adhesion molecule Necl-3/SynCAM-2 localizes to myelinated axons,binds to oligodendrocytes and promotes cell adhesion

Background  

Cell adhesion molecules are plasma membrane proteins specialized in cell-cell recognition and adhesion. Two related adhesion molecules, Necl-1 and Necl-2/SynCAM, were recently described and shown to fulfill important functions in the central nervous system. The purpose of the work was to investigate the distribution, and the properties of Necl-3/SynCAM-2, a previously uncharacterized member of the Necl family with which it shares a conserved modular organization and extensive sequence homology.     

Glutamate-induced apoptosis in neuronal cells is mediated via caspase-dependent and independent mechanisms involving calpain and caspase-3 proteases as well as apoptosis inducing factor (AIF) and this process is inhibited by equine estrogens

Background  

Glutamate, a major excitatory amino acid neurotransmitter, causes apoptotic neuronal cell death at high concentrations. Our previous studies have shown that depending on the neuronal cell type, glutamate-induced apoptotic cell death was associated with regulation of genes such as Bcl-2, Bax, and/or caspase-3 and mitochondrial cytochrome c. To further delineate the intracellular mechanisms, we have investigated the role of calpain, an important calcium-dependent protease thought to be involved in apoptosis along with mitochondrial apoptosis inducing factor (AIF) and caspase-3 in primary cortical cells and a mouse hippocampal cell line HT22.     

The <Emphasis Type="Italic">Adhesion</Emphasis> GPCR GPR125 is specifically expressed in the choroid plexus and is upregulated following brain injury

Background  

GPR125 belongs to the family of Adhesion G protein-coupled receptors (GPCRs). A single copy of GPR125 was found in many vertebrate genomes. We also identified a Drosophila sequence, DmCG15744, which shares a common ancestor with the entire Group III of Adhesion GPCRs, and also contains Ig, LRR and HBD domains which were observed in mammalian GPR125.     

Mitochondrial respiratory chain is involved in insulin-stimulated hydrogen peroxide production and plays an integral role in insulin receptor autophosphorylation in neurons

Background  

Accumulated evidence suggests that hydrogen peroxide (H₂O₂) generated in cells during insulin stimulation plays an integral role in insulin receptor signal transduction. The role of insulin-induced H₂O₂ in neuronal insulin receptor activation and the origin of insulin-induced H₂O₂ in neurons remain unclear. The aim of the present study is to test the following hypotheses (1) whether insulin-induced H₂O₂ is required for insulin receptor autophosphorylation in neurons, and (2) whether mitochondrial respiratory chain is involved in insulin-stimulated H₂O₂ production, thus playing an integral role in insulin receptor autophosphorylation in neurons.     

The <Emphasis Type="Italic">recombination activation gene 1</Emphasis> (<Emphasis Type="Italic">Rag1</Emphasis>) is expressed in a subset of zebrafish olfactory neurons but is not essential for axon targeting or amino acid detection

Background  

Rag1 (Recombination activation gene-1) mediates genomic rearrangement and is essential for adaptive immunity in vertebrates. This gene is also expressed in the olfactory epithelium, but its function there is unknown.