- Human Mesenchymal Stem Cells from Adipose Tissue Differentiated into Neuronal or Glial Phenotype Express Different Aquaporins. [Journal Article]
- MNMol Neurobiol 2016 Dec 05
- Aquaporins (AQPs) are 13 integral membrane proteins that provide selective pores for the rapid movement of water and other uncharged solutes, across cell membranes. Recently, AQPs have been focused f...
Aquaporins (AQPs) are 13 integral membrane proteins that provide selective pores for the rapid movement of water and other uncharged solutes, across cell membranes. Recently, AQPs have been focused for their role in production, circulation, and homeostasis of the cerebrospinal fluid and their importance in several human diseases is becoming clear. This study investigated the time course (0, 14, and 28 days) of AQP1, 4, 7, 8, and 9 during the neural differentiation of human mesenchymal stem cells (MSCs) from adipose tissue (AT). For this purpose, two different media, enriched with serum or B-27 and N1 supplements, were applied to give a stimulus toward neural lineage. After 14 days, the cells were cultured with neuronal or glial differentiating medium for further 14 days. The results confirmed that AT-MSCs could be differentiated into neurons, astrocytes, and oligodendrocytes, expressing not only the typical neural markers but also specific AQPs depending on differentiated cell type. Our data demonstrated that at 28 days, AT-MSCs express only AQP1; astrocytes AQP1, 4, and 7; oligodendrocytes AQP1, 4, and 8; and finally neurons AQP1 and 7. This study provides fundamental insight into the biology of the mesenchymal stem cells and it suggests that AQPs can be potential neural markers.
- Association of dysfunctional synapse defective 1 (SYDE1) with restricted fetal growth - SYDE1 regulates placental cell migration and invasion. [Journal Article]
- JPJ Pathol 2016 Dec 05
- The transcription factor glial cells missing 1 (GCM1) regulates trophoblast differentiation and function during placentation. Decreased GCM1 expression is associated with preeclampsia, suggesting tha...
The transcription factor glial cells missing 1 (GCM1) regulates trophoblast differentiation and function during placentation. Decreased GCM1 expression is associated with preeclampsia, suggesting that abnormal expression of GCM1 target genes may contribute to the pathogenesis of pregnancy complications. Here we identified a novel GCM1 target gene, synapse defective 1 (SYDE1), which encodes a RhoGAP that is highly expressed in human placenta, and demonstrated that SYDE1 promotes cytoskeletal remodelling and cell migration and invasion. Importantly, genetic ablation of murine Syde1 results in small fetuses and placentas with aberrant phenotypes in the placental-yolk sac barrier, maternal-trophoblast interface, and placental vascularization. Microarray analysis revealed altered expression of Renin1, angiotensin I converting enzyme 2, angiotensin II type 1a receptor, and membrane metalloendopeptidase of the renin-angiotensin system in Syde1-knockout placenta, which may compensate the vascular defects to maintain normal blood pressure. As pregnancy proceeds, growth restriction of the Syde1(-/-) fetuses and placentas continues with elevated expression of the Syde1 homologue Syde2 in placenta. Syde2 may compensate for the loss of Syde1 function because SYDE2, but not the GAP-dead SYDE2 mutant, reverses migration and invasion activities of SYDE1-knockdown JAR trophoblast cells. Clinically, we further detected decreased SYDE1 expression in preterm and term IUGR placentas compared with gestational age-matched controls. Our study suggests a novel mechanism for GCM1 and SYDE1 in regulation of trophoblast cell migration and invasion during placental development and that decreased SYDE1 expression is associated with IUGR.
- The Mitochondrial m-AAA Protease Prevents Demyelination and Hair Greying. [Journal Article]
- PGPLoS Genet 2016; 12(12):e1006463
- The m-AAA protease preserves proteostasis of the inner mitochondrial membrane. It ensures a functional respiratory chain, by controlling the turnover of respiratory complex subunits and allowing mito...
The m-AAA protease preserves proteostasis of the inner mitochondrial membrane. It ensures a functional respiratory chain, by controlling the turnover of respiratory complex subunits and allowing mitochondrial translation, but other functions in mitochondria are conceivable. Mutations in genes encoding subunits of the m-AAA protease have been linked to various neurodegenerative diseases in humans, such as hereditary spastic paraplegia and spinocerebellar ataxia. While essential functions of the m-AAA protease for neuronal survival have been established, its role in adult glial cells remains enigmatic. Here, we show that deletion of the highly expressed subunit AFG3L2 in mature mouse oligodendrocytes provokes early-on mitochondrial fragmentation and swelling, as previously shown in neurons, but causes only late-onset motor defects and myelin abnormalities. In contrast, total ablation of the m-AAA protease, by deleting both Afg3l2 and its paralogue Afg3l1, triggers progressive motor dysfunction and demyelination, owing to rapid oligodendrocyte cell death. Surprisingly, the mice showed premature hair greying, caused by progressive loss of melanoblasts that share a common developmental origin with Schwann cells and are targeted in our experiments. Thus, while both neurons and glial cells are dependant on the m-AAA protease for survival in vivo, complete ablation of the complex is necessary to trigger death of oligodendrocytes, hinting to cell-autonomous thresholds of vulnerability to m-AAA protease deficiency.
- Globose, cystic olfactory ensheathing cell tumor: A case report and literature review. [Journal Article]
- OLOncol Lett 2016; 12(5):3981-3986
- Olfactory ensheathing cell tumor (OECT) is one of the most rare intracranial, extra-axial tumors located in the anterior cranial fossa. The present study reports a case of a 34-year-old female patien...
Olfactory ensheathing cell tumor (OECT) is one of the most rare intracranial, extra-axial tumors located in the anterior cranial fossa. The present study reports a case of a 34-year-old female patient who presented with a history of hyposmia for 1 year, as well as a gradual dizziness and emotional lability for 2 months. Magnetic resonance imaging of the brain revealed a globose, well-defined cystic mass at the midline of the anterior cranial fossa, which was confirmed as an OECT by histology and was completely resected by bifrontal craniotomy. According to the immunostaining results, the tumor was positive for vimentin and S100 protein, and negative for epithelial membrane antigen, glial fibrillary acidic protein and cluster of differentiation 57 (also known as Leu-7). The presentation, imaging findings, histopathological examination and histogenesis of OECT are discussed in the present study, along with a literature review.
- Glypican 6 Enhances N-Methyl-D-Aspartate Receptor Function in Human-Induced Pluripotent Stem Cell-Derived Neurons. [Journal Article]
- FCFront Cell Neurosci 2016; 10:259
- The in vitro use of neurons that are differentiated from human induced pluripotent stem cells (hiPSC-neurons) is expected to improve the prediction accuracy of preclinical tests for both screening an...
The in vitro use of neurons that are differentiated from human induced pluripotent stem cells (hiPSC-neurons) is expected to improve the prediction accuracy of preclinical tests for both screening and safety assessments in drug development. To achieve this goal, hiPSC neurons are required to differentiate into functional neurons that form excitatory networks and stably express N-methyl-D-aspartate receptors (NMDARs). Recent studies have identified some astrocyte-derived factors that are important for the functional maturation of neurons. We therefore examined the effects of the astrocyte-derived factor glypican 6 (GPC6) on hiPSC-neurons. When we pharmacologically examined which receptor subtypes mediate L-glutamate (L-Glu)-induced changes in the intracellular Ca(2+) concentrations in hiPSC neurons using fura-2 Ca(2+) imaging, NMDAR-mediated responses were not detected through 7 days in vitro (DIV). These cells were also not vulnerable to excitotoxicity at 7 DIV. However, a 5-days treatment with GPC6 from 3 DIV induced an NMDAR-mediated Ca(2+) increase in hiPSC-neurons and increased the level of NMDARs on the cell surface. We also found that GPC6-treated hiPSC-neurons became responsive to excitotoxicity. These results suggest that GPC6 increases the level of functional NMDARs in hiPSC-neurons. Glial factors may play a key role in accelerating the functional maturation of hiPSC neurons for drug-development applications.
- Guillain-Barré syndrome: a century of progress. [Review]
- NRNat Rev Neurol 2016; 12(12):723-731
- In 1916, Guillain, Barré and Strohl reported on two cases of acute flaccid paralysis with high cerebrospinal fluid protein levels and normal cell counts - novel findings that identified the disease w...
In 1916, Guillain, Barré and Strohl reported on two cases of acute flaccid paralysis with high cerebrospinal fluid protein levels and normal cell counts - novel findings that identified the disease we now know as Guillain-Barré syndrome (GBS). 100 years on, we have made great progress with the clinical and pathological characterization of GBS. Early clinicopathological and animal studies indicated that GBS was an immune-mediated demyelinating disorder, and that severe GBS could result in secondary axonal injury; the current treatments of plasma exchange and intravenous immunoglobulin, which were developed in the 1980s, are based on this premise. Subsequent work has, however, shown that primary axonal injury can be the underlying disease. The association of Campylobacter jejuni strains has led to confirmation that anti-ganglioside antibodies are pathogenic and that axonal GBS involves an antibody and complement-mediated disruption of nodes of Ranvier, neuromuscular junctions and other neuronal and glial membranes. Now, ongoing clinical trials of the complement inhibitor eculizumab are the first targeted immunotherapy in GBS.
- Overexpression of Soluble Fas Ligand following Adeno-Associated Virus Gene Therapy Prevents Retinal Ganglion Cell Death in Chronic and Acute Murine Models of Glaucoma. [Journal Article]
- JIJ Immunol 2016 Dec 15; 197(12):4626-4638
- Glaucoma is a multifactorial disease resulting in the death of retinal ganglion cells (RGCs) and irreversible blindness. Glaucoma-associated RGC death depends on the proapoptotic and proinflammatory ...
Glaucoma is a multifactorial disease resulting in the death of retinal ganglion cells (RGCs) and irreversible blindness. Glaucoma-associated RGC death depends on the proapoptotic and proinflammatory activity of membrane-bound Fas ligand (mFasL). In contrast to mFasL, the natural cleavage product, soluble Fas ligand (sFasL) inhibits mFasL-mediated apoptosis and inflammation and, therefore, is an mFasL antagonist. DBA/2J mice spontaneously develop glaucoma and, predictably, RGC destruction is exacerbated by expression of a mutated membrane-only FasL gene that lacks the extracellular cleavage site. Remarkably, one-time intraocular adeno-associated virus-mediated gene delivery of sFasL provides complete and sustained neuroprotection in the chronic DBA/2J and acute microbead-induced models of glaucoma, even in the presence of elevated intraocular pressure. This protection correlated with inhibition of glial activation, reduced production of TNF-α, and decreased apoptosis of RGCs and loss of axons. These data indicate that cleavage of FasL under homeostatic conditions, and the ensuing release of sFasL, normally limits the neurodestructive activity of FasL. The data further support the notion that sFasL, and not mFasL, contributes to the immune-privileged status of the eye.
- [Beta-adrenoceptor-mediated cyclic AMP signal in different types of cultured nerve cells in normoxic and hypoxic conditions]. [Journal Article]
- MBMol Biol (Mosk) 2016 Sep-Oct; 50(5):838-846
- β-adrenergic neurotransmission is an important factor regulating brain activity such as neuronal and glial survival, plasticity, membrane transport or cellular metabolism. Intracellular β-adrenergic ...
β-adrenergic neurotransmission is an important factor regulating brain activity such as neuronal and glial survival, plasticity, membrane transport or cellular metabolism. Intracellular β-adrenergic signaling, via a stimulatory G protein (Gs), activates two major down-stream effectors, i.e., adenylyl cyclase (AC) and cAMP-dependent protein kinase A (PKA). The aim of this work was to study the ability of endogenous (adrenaline and noradrenaline) and exogenous (isoprenaline) β-adrenergic receptor agonists to increase cAMP in different types of nerve cells. Moreover, we wanted to precisely identify the receptor isoform involved in the observed phenomenon using selective β1-, β2- β3-adrenoceptor blockers. In an additional study, the negative influence of hypoxia on the AC/cAMP intracellular signaling system was tested. The study was conducted in parallel on rat primary glial (astrocytes) cultures, primary neuronal cultures, C6 glioma cells and human T98G glioma cells. The formation of [^(3)H] cAMP by agonists and antagonists was measured in [^(3)H] adenine prelabeled cells under normoxic and hypoxic conditions. The obtained results revealed that adrenaline, noradrenaline and isoprenaline strongly stimulated cAMP production in all tested cell types (with highest potency in C6 glioma cells). In glial and neuronal cells the adrenaline-evoked cAMP effect was mediated mainly by the β1-adrenoceptor, whereas in tumor cells the effect was probably mediated by all three β-subtype specific drugs. The AC/cAMP intracellular signaling system is affected by hypoxic conditions. Considering both physiological and therapeutic importance of β-family receptors the present work characterized the β-adrenoceptor-mediated cAMP signal transduction pathway in different nerve cells in normoxic and hypoxic conditions. The proposed in vitro model of hypoxic conditions may serve as a good model system to study the biological effects of endogenous catecholamines as well as potential therapeutics targeting adrenergic receptors, which are impaired during ischemia in vivo.
- Tissue engineering for neurodegenerative diseases using human amniotic membrane and umbilical cord. [Journal Article]
- CTCell Tissue Bank 2016 Nov 09
- Regenerative medicine, based on the use of stem cells, scaffolds and growth factors, has the potential to be a good approach for restoring damaged tissues of the central nervous system. This study in...
Regenerative medicine, based on the use of stem cells, scaffolds and growth factors, has the potential to be a good approach for restoring damaged tissues of the central nervous system. This study investigated the use of human amniotic mesenchymal stem cells (hAMSC), human amniotic epithelial stem cells (hAESC), and human Wharton's jelly mesenchymal stem cells (hWJMSC) derived from human umbilical cord as a source of stem cells, and the potential of the human amniotic membrane (HAM) as a scaffold and/or source of growth factors to promote nerve regeneration. The hAMSC and hAESC obtained from HAM and the hWJMSC from umbilical cords were cultured in induction medium to obtain neural-like cells. The morphological differentiation of hAMSC, hAESC and hWJMSC into neural-like cells was evident after 4-5 days, when they acquired an elongated and multipolar shape, and at 21 days, when they expressed neural and glial markers. On other way, the HAM was completely decellularized without affecting the components of the basement membrane or the matrix. Subsequently, hAMSC, hAESC and hWJMSC differentiated into neural-like cells were seeded onto the decellularized HAM, maintaining their morphology. Finally, conditioned media from the HAM allowed proliferation of hAMSC, hAESC and hWJMSC differentiated to neural-like cells. Both HAM and umbilical cord are biomaterials with great potential for use in regenerative medicine for the treatment of neurodegenerative diseases.
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- INCOMPLETE REPAIR OF RETINAL STRUCTURE AFTER VITRECTOMY WITH INTERNAL LIMITING MEMBRANE PEELING. [Journal Article]
- RRetina 2016 Nov 08
- CONCLUSIONS: The ultrastructural studies showed that most of ILM peeling area was covered with glial cells during wound healing processes. Retinal changes were found comparable with dissociated optic nerve fiber layer appearance or dimple sign, which were clinically observed with optical coherence tomography.