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glial cell membrane [keywords]
- Apelin in epiretinal membranes of patients with proliferative diabetic retinopathy. [Journal Article]
- Mol Vis 2014.:1122-31.
Formation of epiretinal membranes (ERMs) in the posterior fundus results in visual impairment. ERMs have been associated with numerous clinical conditions, including proliferative diabetic retinopathy (PDR), a neovascular disease. Apelin has been identified as a novel angiogenesis contributor. The aim of this study was to investigate the correlation between apelin and ERMs after PDR.ERM samples were obtained by vitrectomy from 12 subjects with PDR (aged 57±6 years; duration of diabetes 16±7 years), and 12 subjects with idiopathic ERM (aged 68±5 years). The samples were processed for immunohistochemistry and reverse transcription-PCR (RT-PCR). We also analyzed samples from patients with PDR who received an intravitreal injection of bevacizumab (IVB) before vitrectomy.The mRNA expression of apelin was significantly higher in the PDR ERMs than in the idiopathic ERMs. Accordingly, immunohistochemical analysis revealed strong expression of apelin in all eight PDR ERMs without IVB, and was double-labeled with glial fibrillary acidic protein antibody (GFAP), platelet endothelial cell adhesion molecule-1 (CD31), cytokeratin (CK) and vascular endothelial growth factor (VEGF) but not with fibronectin. They were mainly located in the adventitia. In contrast, the expression of apelin was lower in the PDR ERMs after IVB and the idiopathic ERMs.The results showed that apelin was involved in the formation of ERMs and promoted the formation of adventitia, including glial, endothelial, and RPE cells. Bevacizumab blocked the expression of apelin and regressed gliosis and angiogenesis.
- The Pre- and Post-somatic segments of the Human Type I Spiral Ganglion Neurons - Structural and Functional Considerations Related to Cochlear Implantation. [JOURNAL ARTICLE]
- Neuroscience 2014 Oct 11.
Human auditory nerve afferents consist of two separate systems; one is represented by the large type I cells innervating the inner hair cells and the other one by the small type II cells innervating the outer hair cells. Type I spiral ganglion neurons (SGNs) constitute 96% of the afferent nerve population and, in contrast to other mammals, their soma and pre- and post-somatic segments are unmyelinated. Type II nerve soma and fibers are unmyelinated. Histopathology and clinical experience imply that human SGNs can persist electrically excitable without dendrites, thus lacking connection to the organ of Corti. The biological background to this phenomenon remains elusive. We analyzed the pre- and post-somatic segments of the type I human SGNs using immunohistochemistry and transmission electron microscopy (TEM) in normal and pathological conditions. These segments were found surrounded by non-myelinated Schwann cells (NMSC) showing strong intracellular expression of laminin-β2/collagen IV. These cells also bordered the perikaryal entry zone and disclosed surface rugosities outlined by a folded basement membrane (BM) expressing laminin-β2 and collagen IV. It is presumed that human large SGNs are demarcated by three cell categories: a) myelinated Schwann cells, b) non-myelinated Schwann cells (NMSC) and c) satellite glial cells (SGCs). Their BMs express laminin-β2/collagen IV and reaches the BM of the sensory epithelium at the habenula perforata. We speculate that the NMSC protect SGNs from further degeneration following dendrite loss. It may give further explanation why SGNs can persist as electrically excitable monopolar cells even after long time deafness, a blessing for the deaf treated with cochlear implantation.
- Guanosine Protects Glial Cells Against 6-Hydroxydopamine Toxicity. [JOURNAL ARTICLE]
- Adv Exp Med Biol 2014 Oct 14.
Increasing body of evidence indicates that neuron-neuroglia interaction may play a key role in determining the progression of neurodegenerative diseases including Parkinson's disease (PD), a chronic pathological condition characterized by selective loss of dopaminergic (DA) neurons in the substantia nigra. We have previously reported that guanosine (GUO) antagonizes MPP(+)-induced cytotoxicity in neuroblastoma cells and exerts neuroprotective effects against 6-hydroxydopamine (6-OHDA) and beta-amyloid-induced apoptosis of SH-SY5Y cells. In the present study we demonstrate that GUO protected C6 glioma cells, taken as a model system for astrocytes, from 6-OHDA-induced neurotoxicity. We show that GUO, either alone or in combination with 6-OHDA activated the cell survival pathways ERK and PI3K/Akt. The involvement of these signaling systems in the mechanism of the nucleoside action was strengthened by a reduction of the protective effect when glial cells were pretreated with U0126 or LY294002, the specific inhibitors of MEK1/2 and PI3K, respectively. Since the protective effect on glial cell death of GUO was not affected by pretreatment with a cocktail of nucleoside transporter blockers, GUO transport and its intracellular accumulation were not at play in our in vitro model of PD. This fits well with our data which pointed to the presence of specific binding sites for GUO on rat brain membranes. On the whole, the results described in the present study, along with our recent evidence showing that GUO when administered to rats via intraperitoneal injection is able to reach the brain and with previous data indicating that it stimulates the release of neurotrophic factors, suggest that GUO, a natural compound, by acting at the glial level could be a promising agent to be tested against neurodegeneration.
- Histomorphological spectrum and immunohistochemical characterization of hemangioblastomas: An entity of unclear histogenesis. [Journal Article]
- Indian J Pathol Microbiol 2014 Oct-Dec; 57(4):542-8.
Hemangioblastomas (HBs) are rare WHO grade I neoplasms of uncertain histogenesis. Most are sporadic and association with von Hippel-Lindau disease (VHL) is uncommon.Histomorphological and immunohistochemical evaluation of 24 cases of HBs was done.Age range was 15-68 yrs (median: 30 yrs) with male:Female of 1.2:1 (M-13; F-11). Cerebellum was commonest location (n = 20), one each was seen in brain stem, cervical spinal cord, fourth ventricle and frontal lobe, respectively. VHL association was noted in 5 cases. Four cases were recurrent in nature of which 3 were in association with vHL. Histologically, reticular variant was the predominant subtype (n = 15), 5 were of cellular variant and 4 were mixed. Nuclear pleomorphism, nuclear cytoplasmic inclusions, cytoplasmic vacuolation were noted in the stromal cells in varying proportions. Immunohistochemical evaluation was successful in only 11 cases and of which 8 showed stromal cell positivity for alpha-inhibin. CD56 (NCAM), Nestin and synaptophysin positivity was seen in 6, 7 and 4 cases, respectively. Nestin positivity was noted in stromal cells only and no reactivity with the endothelial cells seen. S-100 protein and NSE positivity was seen in 8 and 10 cases, respectively. Glial fibrillary acidic protein (GFAP) showed two distinct patterns of immunoreactivity - scattered stromal cell positivity (n:5) and pattern of reactive astrogliosis positivity (n:10). CD44 positivity was noted in 5 cases. VEGF and EGFR positivity was seen in 5 cases each. None of the cases showed positivity for epithelial membrane antigen and no stromal cells in any of the cases showed positivity for CD34 and CD31.HBs can occur in throughout the neuroaxis. Cerebellum is the commonest site of occurrence for HBs and uncommonly can occur in the supratentorial compartment and spinal cord. Its association with vHL is uncommon and no histological or immunohistochemical correlation was identified with the same.
- Diagnostic and therapeutic potentials of exosomes in CNS diseases. [JOURNAL ARTICLE]
- Brain Res 2014 Oct 7.
A newly discovered cell-to-cell communication system involves small, membrane-enveloped nanovesicles, called exosomes. We describe here how these extracellular nanoparticles were discovered and how it became gradually apparent that they play fundamental roles in regulation of physiological functions and pathological processes. Exosomes enable intercellular communication by transporting genetic material, proteins and lipids to cells in their vicinity or at distant sites, and subsequently regulating functions of targeted cells. Relatively recent experiments indicate that exosomes are released also by CNS cells, including cortical and hippocampal neurons, glial cells, astrocytes and oligodendrocytes, and that exosomes have significant impact on pathophysiology of the brain. How it is decided what individual exosomes will carry to their targets is not understood, but it appears that the contents may represent "signature cargos" that are characteristic for various conditions. Exploration of such characteristics could result in discovery of novel diagnostic biomarkers. Exosomes are also promising as a vehicle for therapeutic delivery of micro RNA or other compounds. How to deliver exosomes to selected sites has been a tantalizing question. Recent experiments revealed that at least some exosomes carry antibodies on their surface, suggesting that it may be feasible to deliver exosomes to unique sites based on the recognition of antigens by those antibodies. This discovery implies that rather precise targeting of both natural and engineered exosomes may be feasible. This would reduce distribution volume of therapeutics, and consequently minimize their side effects. This article is part of a Special Issue entitled Neuroimmunology in Health And Disease.
- Glycine transporters GlyT1 and GlyT2 are differentially modulated by glycogen synthase kinase 3β [JOURNAL ARTICLE]
- Neuropharmacology 2014 Oct 6.
Inhibitory glycinergic neurotransmission is terminated by the specific glycine transporters GlyT1 and GlyT2 which actively reuptake glycine from the synaptic cleft. GlyT1 is associated with both glycinergic and glutamatergic pathways, and is the main regulator of the glycine levels in the synapses. GlyT2 is the main supplier of glycine for vesicle refilling, a process that is vital to preserve the quantal glycine content in synaptic vesicles. Therefore, to control glycinergic neurotransmission efficiently, GlyT1 and GlyT2 activity must be regulated by diverse neuronal and glial signaling pathways. In this work, we have investigated the possible functional modulation of these transporters, GlyT1 and GlyT2, by glycogen synthase kinase 3 (GSK3β). This kinase is involved in mood stabilization, neurodegeneration and plays a major role in plasticity at excitatory and inhibitory synapses. The co-expression of GSK3β with GlyT1 or GlyT2 in COS-7 cells and Xenopus laevis oocytes, leads to inhibition and stimulation of GlyT1 and GlyT2 activities, respectively, with a decrease of GlyT1, and an increase in GlyT2 levels at the plasma membrane. The specificity of these changes is supported by the antagonism exerted by a catalytically inactive form of the kinase and through inhibitors of GSK3β such as lithium chloride and TDZD-8. GSK3β also increases the incorporation of (32)Pi into GlyT1 and decreases that of GlyT2. The pharmacological inhibition of the endogenous GSK3β in neuron cultures of brainstem and spinal cord, also leads to an opposite modulation of GlyT1 and GlyT2. Our results suggest that GSK3β is important for stabilizing and/or controlling the expression of functional GlyTs on the neural cell surface. This could represent a more general process underlying CNS synaptic plasticity where GSK3β controls neuronal proteins that are crucial to the proper functioning of inhibitory and excitatory fast neurotransmission.
- Insulin involved Akt/ERK and Bcl-2/Bax pathways against oxidative damages in C6 glial cells. [JOURNAL ARTICLE]
- J Recept Signal Transduct Res 2014 Oct 9.:1-7.
Abstract Insulin, a hypoglycemic hormone, has multiple functions in the brain. The aim of this study to identify the mechanisms of insulin in hydrogen peroxide (H2O2)-induced toxicity in the C6 glial cells. Cytotoxicity, lactate dehydrogenase, nitric oxide, reactive oxygen species and calcium ion, lipid peroxidation, protein oxidation and glutathione levels were determined. Signaling pathway molecules were assessed by western blotting and RT-PCR. The results showed that treatment with insulin reduced the cell death and cell membrane damages against H2O2-induced toxicity. Furthermore, insulin interfered H2O2-induced intracellular generation of reactive oxygen species and calcium-ion transport, apoptosis, including lipid and protein oxidation products. Cells treated with insulin reverted H2O2-induced suppression of reduced glutathione levels by blocking oxidized glutathione. Moreover, insulin treatment activates Akt, restores ERK1/2 and Bcl-2 by preventing Bax and Bax/Bcl-2 ratio. Our results suggest that treatment of insulin exerts potential role against 24 h of H2O2-induced toxicity in C6 cells.
- Ganglioside GD3 Is Required for Neurogenesis and Long-Term Maintenance of Neural Stem Cells in the Postnatal Mouse Brain. [Journal Article]
- J Neurosci 2014 Oct 8; 34(41):13790-800.
The maintenance of a neural stem cell (NSC) population in mammalian postnatal and adult life is crucial for continuous neurogenesis and neural repair. However, the molecular mechanism of how NSC populations are maintained remains unclear. Gangliosides are important cellular membrane components in the nervous system. We previously showed that ganglioside GD3 plays a crucial role in the maintenance of the self-renewal capacity of NSCs in vitro. Here, we investigated its role in postnatal and adult neurogenesis in GD3-synthase knock-out (GD3S-KO) and wild-type mice. GD3S-KO mice with deficiency in GD3 and the downstream b-series gangliosides showed a progressive loss of NSCs both at the SVZ and the DG of the hippocampus. The decrease of NSC populations in the GD3S-KO mice resulted in impaired neurogenesis at the granular cell layer of the olfactory bulb and the DG in the adult. In addition, defects of the self-renewal capacity and radial glia-like stem cell outgrowth of postnatal GD3S-KO NSCs could be rescued by restoration of GD3 expression in these cells. Our study demonstrates that the b-series gangliosides, especially GD3, play a crucial role in the long-term maintenance NSC populations in postnatal mouse brain. Moreover, the impaired neurogenesis in the adult GD3S-KO mice led to depression-like behaviors. Thus, our results provide convincing evidence linking b-series gangliosides deficiency and neurogenesis defects to behavioral deficits, and support a crucial role of gangliosides in the long-term maintenance of NSCs in adult mice.
- Evaluation of proliferating cell abundance and phenotypes in proliferative diabetic retinopathy. [JOURNAL ARTICLE]
- Graefes Arch Clin Exp Ophthalmol 2014 Oct 8.
The aim of this work is to evaluate the abundance, origins, and phenotypes of actively proliferating cells in proliferative diabetic retinopathy (PDR).Eleven epiretinal membranes from patients undergoing surgery for PDR were evaluated by indirect immunofluorescence for evidence of cell proliferation using the nuclear cell proliferation marker Ki67 and for cell identities using glial fibrillary acidic protein (GFAP), glutamine synthetase, and α-smooth muscle actin (αSMA).Ki67 positivity was consistently rare in PDR epiretinal membranes at 3.02 ± 1.42 % of the total cell population. The majority of the Ki67-positive cells were also positive for GFAP (74.0 %) with lower proportions positive for αSMA (30.7 %) and glutamine synthetase (1.5 %). Co-localization studies using glial and myoid markers revealed that virtually all (92 %) of the αSMA-positive cells are also GFAP positive and thus derive from glia.Entry into cell cycle and thus cell proliferation appears to be a rare phenomenon in PDR involving only a small percentage of the total cell population. Glia and/or glial-derived myofibroblasts appear to be the predominate cell types in epiretinal scar tissues and also account for the majority of the actively proliferating cells.
- Magnetic resonance imaging of intracranial hemangiopericytoma and correlation with pathological findings. [JOURNAL ARTICLE]
- Oncol Lett 2014 Nov; 8(5):2140-2144.
The present study aimed to evaluate the radiological and pathological features of intracranial hemangiopericytoma, and improve the understanding of this tumor. A retrospective analysis of radiological and pathological features of five cases of intracranial hemangiopericytoma was conducted between 2006 and 2012 in the Second Xiangya Hospital of Central South University. A total of five cases (three males and two females; aged 37-60 years) were enrolled. Magnetic resonance imaging revealed that the lesions were lobulated with iso-intensity T1-weighted image signals and slightly long T2-weighted image signals. Cystic degeneration, necrosis and flow void were observed. The case with the lesion located under the tentorium cerebelli exhibited compression of the fourth ventricle with lateral ventricle dilatation hydrocephalus. In all cases, the solid section of the lesion was markedly enhanced following injection of the contrast agent, and intratumoral vessels were observed. No case exhibited the dural tail sign. Immunohistochemical examination revealed positive expression of cluster of differentiation 34(CD34), vimentin and CD99, and negative expression of epithelial membrane antigen, S100 and glial fibrillary acidic protein. Proliferating cell nuclear antigen Ki-67 immunohistochemical staining revealed that <5% of cells expressed Ki-67 in two cases and 5-10% of cells expressed Ki-67 in three cases. In conclusion, intracranial hemangiopericytoma exhibits certain distinctive characteristics in radiological examination, allowing for improved diagnosis. However, pathological examination is required for confirmation.