302 research outputs found
Mechanisms of axonal degeneration in EAE - lessons from CNTF and MHC I knockout mice
No full textThe major pathological hallmarks of multiple sclerosis (MS) comprise inflammation, demyelination with associated gliosis and axonal damage, which most likely correlates with persisting disability. Axonal damage can occur by several mechanisms. This article focuses on myelin disintegration and direct immune attack on axons by CD8-positive T-cells as two possible scenarios for axonal injury. As protoypic models, we investigated experimental autoimmune encephalomyelitis (EAE) in ciliary neurotrophic factor gene knockout mice (CNTF-/- mice) with severe myelin pathology and EAE in beta-2 microglobulin gene knockout mice (beta 2m-/- mice) lacking CD8-positive T-cells. The results from these studies indicate that the trigger attack for axonal injury even in a well-defined experimental design can be multi-facetted. No single factor seems to be absolutely necessary for the initiation of the process, but they rather act in concert and orchestrate tissue destruction, inflammation and regeneration. Some mechanisms of primary or secondary axonal damage may be shared between inflammatory and degenerative diseases of the nervous system, thereby establishing a link which might be of importance for future therapeutic strategies. (c) 2005 Elsevier B.V. All rights reserved
Contribution of Ca2+-permeable AMPA/KA receptors to glutamate-induced Ca2+ rise in embryonic lumbar motoneurons in situ
No full textIntracellular Ca2+ ([Ca2+](i)) was fluorometrically measured with fura-2 in lumbar motoneurons of acutely isolated spinal cord slices from embryonic rats. In ester-loaded cells, bath-applied glutamate (3 mu M to 1 mM) evoked a [Ca2+](i) increase by up to 250 nM that was abolished by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) plus 2-amino-5-phosphonovalerate (APV). CNQX or APV alone reduced the response by 82 and 25%, respectively. The glutamatergic agonists kainate (KA), quisqualate (QUI), and S-alpha-amino-3-hydroxy-5-methyl-4-isoxalone (S-AMPA) evoked a similar [Ca2+](i) transient as glutamate. N-methyl-D-aspartate (NMDA) was only effective to increase [Ca2+](i) in Mg2+-free saline, whereas [1S,3R]-1-aminocyclopentane-1,3-dicarboxylic acid([1S,3R]ACPD) had no effect. The glutamate-induced [Ca2+](i) rise was suppressed in Ca2+-free superfusate. Depletion of Ca2+ stores with cyclopiazonic acid (CPA) did not affect the response. Thirty-six percent of the [Ca2+](i) increase in response to membrane depolarization induced by a 50 mM K+ solution persisted on combined application of the voltage-gated Ca2+ channel blockers nifedipine, omega-conotoxin-GVIA and omega-agatoxin-IVA. In fura-2 dialyzed motoneurons, the glutamate-induced [Ca2+](i) increase was attenuated by similar to 70% after changing from current to voltage clamp. Forty percent of the remaining [Ca2+], transient and 20% of the concomitant inward current of 0.3 nA were blocked by Joro spider toxin-3 (JSTX). The results show that voltage-gated Ca2+ channels, including a major portion of R-type channels, constitute the predominant component of glutamate-induced [Ca2+](i) rises. NMDA and Ca2+-permeable KA/AMPA receptors contribute about equally to the remaining component of the Ca2+ rise. The results substantiate previous assumptions that Ca2+ influx through JSTX-sensitive KA/AMPA receptors is involved in (trophic) signaling in developing motoneurons
Contribution of Ca2+-permeable AMPA/KA receptors to glutamate-induced Ca2+ rise in embryonic lumbar motoneurons in situ
No full textIntracellular Ca2+ ([Ca2+](i)) was fluorometrically measured with fura-2 in lumbar motoneurons of acutely isolated spinal cord slices from embryonic rats. In ester-loaded cells, bath-applied glutamate (3 mu M to 1 mM) evoked a [Ca2+](i) increase by up to 250 nM that was abolished by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) plus 2-amino-5-phosphonovalerate (APV). CNQX or APV alone reduced the response by 82 and 25%, respectively. The glutamatergic agonists kainate (KA), quisqualate (QUI), and S-alpha-amino-3-hydroxy-5-methyl-4-isoxalone (S-AMPA) evoked a similar [Ca2+](i) transient as glutamate. N-methyl-D-aspartate (NMDA) was only effective to increase [Ca2+](i) in Mg2+-free saline, whereas [1S,3R]-1-aminocyclopentane-1,3-dicarboxylic acid([1S,3R]ACPD) had no effect. The glutamate-induced [Ca2+](i) rise was suppressed in Ca2+-free superfusate. Depletion of Ca2+ stores with cyclopiazonic acid (CPA) did not affect the response. Thirty-six percent of the [Ca2+](i) increase in response to membrane depolarization induced by a 50 mM K+ solution persisted on combined application of the voltage-gated Ca2+ channel blockers nifedipine, omega-conotoxin-GVIA and omega-agatoxin-IVA. In fura-2 dialyzed motoneurons, the glutamate-induced [Ca2+](i) increase was attenuated by similar to 70% after changing from current to voltage clamp. Forty percent of the remaining [Ca2+], transient and 20% of the concomitant inward current of 0.3 nA were blocked by Joro spider toxin-3 (JSTX). The results show that voltage-gated Ca2+ channels, including a major portion of R-type channels, constitute the predominant component of glutamate-induced [Ca2+](i) rises. NMDA and Ca2+-permeable KA/AMPA receptors contribute about equally to the remaining component of the Ca2+ rise. The results substantiate previous assumptions that Ca2+ influx through JSTX-sensitive KA/AMPA receptors is involved in (trophic) signaling in developing motoneurons
Ciliary neurotrophic factor (CNTF): physiologische und pharmakologische Effekte in der Retina
No full textPrincipios tóxicos de Solanum malacoxylon Sendtner. I. Acción de fracción con solventes selectivos sobre el metabolismo fosfo-calcico y tejidos blandos del conejo.
No full textSe separaron seis fracciones químicamente diferentes de Solanum malacoxylon Sendtner por extracción con solventes selectivos, y se ensayó la acción de estas fracciones sobre el metabolismo del calcio y fósforos en conejos
PRINCIPIOS TOXICOS DE SOLANUM MALACOXYLON SENDTNER. l. ACCION DE FRACCIONES SEPARADAS POR EXTRACCION CON SOLVENTES SELECTIVOS SOBRE EL METABOLISMO FOSFO-CALCICO y TEJIDOS BLANDOS DEL CONEJO
No full textSe separaron seis fracciones químicamente diferentes de
hojas de Solanum malacoxylon Sendtner por extracción con solventes
selectivos, y se ensayó la acción de estas fracciones sobre el metabolismode
calcio y fósforo en conejos. Dos de estas fracciones elevaron
los niveles de fósforo inorgánico en sangre y produjeron calificaciones
en tejidos blandos; su composición indica que el efecto metabólico
debe atríbuirse a glicósidos, mono u oligosacáridos, aminoácidos u
oligopéptidos
THE GENE FOR CILIARY NEUROTROPHIC FACTOR (CNTF) MAPS TO MURINE CHROMOSOME 19 AND ITS EXPRESSION IS NOT AFFECTED IN THE HEREDITARY MOTONEURON DISEASE WOBBLER OF THE MOUSE
No full textKAUPMANN K, SENDTNER M, STOCKLI KA, Jockusch H. THE GENE FOR CILIARY NEUROTROPHIC FACTOR (CNTF) MAPS TO MURINE CHROMOSOME 19 AND ITS EXPRESSION IS NOT AFFECTED IN THE HEREDITARY MOTONEURON DISEASE WOBBLER OF THE MOUSE. EUROPEAN JOURNAL OF NEUROSCIENCE. 1991;3(11):1182-1186.The cDNA for ciliary neurotrophic factor (CNTF), a polypeptide involved in the survival of motoneurons in mammals, has recently been cloned (Stockli et al., Nature, 342, 920-923, 1989; Lin et al., Science, 246, 1023-1025, 1989). We have now localized the corresponding gene Cntf to chromosome 19 in the mouse, using an interspecific cross between Mus spretus and Mus musculus domesticus. The latter was carrying the gene wobbler (wr) for spinal muscular atrophy. DNA was prepared from backcross individuals and typed for the segregation of species-specific Cntf restriction fragments in relation to DNA markers of known chromosomal location. The M.spretus allele of Cntf cosegregated with chromosome 19 markers and mapped closely to Ly-1, to a region of mouse chromosome 19 with conserved synteny to human chromosome 11q. Cntf is not linked to wr, and the expression of CNTF mRNA and protein appears close to normal in facial and sciatic nerves of affected (wr/wr) mice, suggesting that motoneuron degeneration of wobbler mice has its origin in defects other than reduced CNTF expression
Survival effect of ciliary neurotrophic factor (CNTF) on chick embryonic motoneurons in culture: comparison with other neurotrophic factors and cytokines
No full textIn previous studies, it has been demonstrated that ciliary neurotrophic factor (CNTF) has a potent survival effect on various populations of neurons in culture, in particular, neurons isolated from chick ciliary, dorsal root sensory, and sympathetic ganglia (Barbin et al., 1984). After recent investigations demonstrated that CNTF prevents the degeneration of motoneurons in newborn rats after axonal lesion (Sendtner et al., 1990), the question arose as to whether CNTF also has a survival effect on embryonic chick motoneurons at the developmental stage where physiological cell death occurs. To study this, it was essential to develop an isolation and culture procedure for the survival of chick E6 spinal motoneurons in which non-neuronal cells were eliminated and the motoneurons were highly enriched. In these cultures, virtually all of the initially plated motoneurons survived for at least 3 d in the presence of muscle extract, which was chosen as a positive control. Retrograde labeling of the motoneurons prior to their isolation showed that there is more than an 80% enrichment for motoneurons by the method used. The retrogradely labeled neurons also fulfilled the morphological criteria (diameter of neurons, appearance of processes) to identify motoneurons independent of retrograde labeling. Under these conditions, CNTF at a concentration of 1.5 ng/ml (EC50, 0.023 ng/ml) supported maximally 64% of the initially plated spinal motoneurons after 3 d and 53% after 6 d (the longest time period investigated). Other neurotrophic factors, such as NGF, brain-derived neurotrophic factor (BDNF), and neurotrophin-3, had no survival effect at all, even at concentrations up to 10 micrograms/ml for NGF and BDNF.(ABSTRACT TRUNCATED AT 250 WORDS)</jats:p
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