Oxidative stress and impaired oligodendrocyte precursor cell differentiation in neurological disorders

Cellular and Molecular Life Sciences - Oligodendrocyte precursor cells (OPCs) account for 5% of the resident parenchymal central nervous system glial cells. OPCs are not only a back-up for the loss...     

Receiving mixed signals: uncoupling oligodendrocyte differentiation and myelination

The development and maturation of an oligodendroglial cell is comprised of three intimately related processes that include proliferation, differentiation, and myelination. Here we review how proliferation and differentiation are controlled by distinct molecular mechanisms and discuss whether differentiation is merely a default of inhibited proliferation. We then address whether differentiation and myelination can be uncoupled in a similar manner. This task is particularly challenging because an oligodendrocyte cannot myelinate without first differentiating, and these processes are therefore not mutually exclusive. Is it solely the presence of the axon that distinguishes a differentiated oligodendrocyte from a myelinating one? Uncoupling these two processes requires identifying specific signals that regulate myelination without affecting the differentiation process. We will review current understanding of the relationship between differentiation and myelination and discuss whether these two processes can truly be uncoupled.     

Regulation of oligodendrocyte precursor migration during development, in adulthood and in pathology

Oligodendrocytes are the myelin-forming cells in the central nervous system (CNS). These cells originate from oligodendrocyte precursor cells (OPCs) during development, and they migrate extensively from oligodendrogliogenic niches along the neural tube to colonise the entire CNS. Like many other such events, this migratory process is precisely regulated by a battery of positional and signalling cues that act via their corresponding receptors and that are expressed dynamically by OPCs. Here, we will review the cellular and molecular basis of this important event during embryonic and postnatal development, and we will discuss the relevance of the substantial number of OPCs existing in the adult CNS. Similarly, we will consider the behaviour of OPCs in normal and pathological conditions, especially in animal models of demyelination and of the demyelinating disease, multiple sclerosis. The spontaneous remyelination observed after damage in demyelinating pathologies has a limited effect. Understanding the cellular and molecular mechanisms underlying the biology of OPCs, particularly adult OPCs, should help in the design of neuroregenerative strategies to combat multiple sclerosis and other demyelinating diseases.     

Inhibition of phosphodiesterase activity of human spermatozoa by spermine

Summary Sperm motility and metabolism are dependent upon the levels of cyclic AMP. Our studies have demonstrated that spermine by inhibiting sperm phosphodiesterase activity could regulate sperm physiology.     

Inhibition of phosphodiesterase activity of human spermatozoa by spermine.

Sperm motility and metabolism are dependent upon the levels of cyclic AMP. Our studies have demonstrated that spermine by inhibiting sperm phosphodiesterase activity could regulate sperm physiology.     

Inhibition of cyclic 3′, 5′-nucleotide phosphodiesterase activity by diuretics and other agents

Résumé Différent composés organo-mercuriels ainsi que l'acide éthacrinique inhibent les phosphodiestérases de l'AMP cyclique, du cur de cobaye, de buf et de rat, des plaquettes de rat et de l'homme ainsi que du cerveau de rat.     

Stem cells from human apical papilla decrease neuro-inflammation and stimulate oligodendrocyte progenitor differentiation via activin-A secretion

Secondary damage following spinal cord injury leads to non-reversible lesions and hampering of the reparative process. The local production of pro-inflammatory cytokines such as TNF-α can exacerbate these events. Oligodendrocyte death also occurs, followed by progressive demyelination leading to significant tissue degeneration. Dental stem cells from human apical papilla (SCAP) can be easily obtained at the removal of an adult immature tooth. This offers a minimally invasive approach to re-use this tissue as a source of stem cells, as compared to biopsying neural tissue from a patient with a spinal cord injury. We assessed the potential of SCAP to exert neuroprotective effects by investigating two possible modes of action: modulation of neuro-inflammation and oligodendrocyte progenitor cell (OPC) differentiation. SCAP were co-cultured with LPS-activated microglia, LPS-activated rat spinal cord organotypic sections (SCOS), and LPS-activated co-cultures of SCOS and spinal cord adult OPC. We showed for the first time that SCAP can induce a reduction of TNF-α expression and secretion in inflamed spinal cord tissues and can stimulate OPC differentiation via activin-A secretion. This work underlines the potential therapeutic benefits of SCAP for spinal cord injury repair.     

Allergic encephalomyelitis: Inhibition of cellular passive transfer by exogenous and endogenous steroids

Zusammenfassung Injektionen des Antientzündungssteroids Dexamethasone oder eine Hypersekretion des endogenen Kortikosteroids als eine Reaktion zum unspezifischen Stress verhindern die zelluläre passive Übertragung allergischer Enzephalomyelitis. Deshalb kann angenommen werden, dass Steroide die enzephalitogene Wirkung von vollkommen immunisierten Lymphoidzellen verhindern.

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Supported by National Multiple Sclerosis Society grant No. 536A10 and United States Public Health Service grant No. HD 02261-03. R.Sowinski and B. H.Brown assisted in the experiments. Dr. H. B.Devlin, Parke Davis & Co., Detroit, kindly supplied the pertussis vaccine.     

Inhibition of endogenous TSH in rats by antiserum to bovine TSH

Riassunto Gli autori hanno ottenuto in conigli un siero anti-TSH usando come antigene ormone bovino. Questo siero inibisce il TSH endogeno di ratti nutriti con dieta di Remington e trattati con tiouracile, impedendo cosi la formazione della iperplasia tiroidea. È stato anche osservato che il trattamento con siero anti-TSH mantiene normale il rapporto MIT/DIT cancellando le salienti alterazioni indotte dal trattamento con tiouracile.     

TRAIL promotes the survival,migration and proliferation of vascular smooth muscle cells

Human and rat primary sub-cultured vascular smooth muscle cells (VSMCs) showed clear expression of the death receptors TRAIL-R1 and TRAIL-R2; however, recombinant soluble TRAIL did not induce cell death when added to these cells. TRAIL tended to protect rat VSMCs from apoptosis induced either by inflammatory cytokines tumor necrosis factor- + interleukin-1 + interferon- or by prolonged serum withdrawal, and promoted a significant increase in VSMC proliferation and migration. Of note, all the biological effects induced by TRAIL were significantly inhibited by pharmacological inhibitors of the ERK pathway. Western blot analysis consistently showed that TRAIL induced a significant activation of ERK1/2, and a much weaker phosphorylation of Akt, while it did not affect the p38/MAPK pathway. Taken together, these data strengthen the notion that the TRAIL/TRAIL-R system likely plays a role in the biology of the vascular system by affecting the survival, migration and proliferation of VSMCs.Received 6 May 2004; received after revision 7 June 2004; accepted 8 June 2004     

Erythropoietic stimulation enhances,and erythropoietic inhibition suppresses,multidirectional differentiation in 5-day transient endogenous spleen colonies

Summary Transient endogenous spleen colonies were found to be composed of either erythroid, granuloid or megakaryocytic cells, or mixtures of these cell types. Independently of the directions of differentiation of the colonies their formation was uniformly stimulated by bleeding and almost completely prevented by hypertransfusion. It is suggested that cells which form these colonies constitute a separate class of pluripotential hemopoietic progenitors, whose differentiation in either direction passes the stage sensitive to erythropoiesis-modulating factors.Acknowledgments. I am indebted to Drs C. Szczylik and J. Grzybowski for fruitful discussions and to Ms Elzbieta Rychowiecka for expert technical assistance. This work was supported in part by grant 10.5 from Polish Academy of Sciences.     

Effect of carbenoxolone on phosphodiesterase and prostaglandin synthetase activities

Summary Carbenoxolone inhibited in vitro cAMP and cGMP phosphodiesterases in a concentration-dependent and noncompetitive manner. Prostaglandin synthetase activity of rabbit kidney medulla was slightly stimulated by carbenoxolone 0.1–0.5 mM, but inhibited by higher concentrations.Acknowledgment. Supported by a grant from the Orion and Medica Scientific Foundation, Finland.     

Effect of carbenoxolone on phosphodiesterase and prostaglandin synthetase activities.

Carbenoxolone inhibited in vitro cAMP and cGMP phosphodiesterases in a concentration-dependent and noncompetitive manner. Prostaglandin synthetase activity of rabbit kidney medulla was slightly stimulated by carbenoxolone 0.1--0.5 mM, but inhibited by higher concentrations.     

Interaction of smooth muscle relaxant drugs with calmodulin and cyclic nucleotide phosphodiesterase

Some smooth muscle relaxant drugs with an unknown mechanism of action have been tested for their interaction with calmodulin and with calmodulin-induced cyclic nucleotide phosphodiesterase (PDE) activity. The affinity of these drugs for calmodulin does not parallel their inhibitory effect on the calmodulin activation of PDE. The lack of parallelism could be due to a binding of the drugs to different sites on calmodulin; furthermore a binding of papaverine, octylonium bromide and felodipine to PDE molecule might also be considered to explain their inhibitory effect on PDE basal activity. The myolytic effect of octylonium bromide and pinaverium bromide may be due to their interaction with calmodulin-dependent systems.     

Interaction of smooth muscle relaxant drugs with calmodulin and cyclic nucleotide phosphodiesterase

Summary Some smooth muscle relaxant drugs with an unknown mechanism of action have been tested for their interaction with calmodulin and with calmodulin-induced cyclic nucleotide phosphodiesterase (PDE) activity. The affinity of these drugs for calmodulin does not parallel their inhibitory effect on the calmodulin activation of PDE. The lack of parallelism could be due to a binding of the drugs to different sites on calmodulin; furthermore a binding of papaverine, octylonium bromide and felodipine to PDE molecule, might also be considered to explain their inhibitory effect on PDE basal activity. The myolytic effect of octylonium bromide and pinaverium bromide may be due to their interaction with calmodulin-dependent systems.