摘要:

AbstractThe terminal step in the biosynthesis of substance P is the conversion of its glycine‐extended precursor to the mature, amidated peptide by the α‐amidating enzyme. This posttranslational modification was demonstrated in cultured dissociated sensory neurons of dorsal root ganglia from neonatal rats. An assay was developed to quantitate both substance P and its precursor peptide in these cells. More than 90% of these two peptide was present as mature peptide in uncultured cells. In contrast, after 8 days in culture, about 85% of the peptides was the precursor, which increased 200‐fold, whereas the level of substance P itself tripled during this culturing period. Since α‐amidating enzyme requires ascorbate for activity, this reducing agent was added to the culture medium. Ascorbate induced a dose‐dependent rise in the percentage of amidated peptide, with an apparent Kmof 20μM. After 5 days of culturing in the presence of 500 μ ascorbate, substance P increased 8‐fold, constituting 70% of the total. The α‐amidating enzyme also needs copper for activity. Even with 500 μM ascorbate in the culture medium, the copper chelator diethyldithiocarbamate dose‐dependently reduced substance P synthesis by the sensory neurons, with a concomitant increase in its precursor peptide. These results suggest the presence of α‐amidating enzyme in sensory neurons of dorsal root ganglia. It is likely that conversion of other glycine‐extended precursors to their mature peptides in cell cultures would also require ascorbate and copp

ISSN:0360-4012    

DOI:10.1002/jnr.490370113

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractWe examined the evolution of1H‐NMR detectable metabolites in rat cerebellum fro the postnatal day 1–25, a period associated with intense metabolic changes as well as physiological and morphological modifications. The unexpected result reported here is the existence of a high concentration of acetate in neonatal rat cerebellum, progressively decreasing with age and maturation. In contrast, the cerebellum content of various metabolites such asN‐acetyl‐L‐as‐partate (NAA), glutamate, and aspartate increases from the first day onward. © 1994 Wil

ISSN:0360-4012    

DOI:10.1002/jnr.490370114

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractAstrocytes appear star‐shaped in the brain, increasingly so after injury. When astroglia are cultures in serum‐containing medium, they exhibit a flat, fibroblast‐like morphology. In serum‐free medium, astrocytes become stellate, with many long processes. The serine protease α‐thrombin mimics the effects of serum at subnanomolar concentractions, whereas the thrombin‐inhibiting serpin, protease nexin I (PNI), reverses the thrombin effect. In our current experiements, murine neonatal spinal cord astrocytes became stellate after 4 hr in serum‐free medium, while cortical astrocytes requires 12 hr in serum‐free medium for stellation. Astrocytes from either region flattened after 60 min in medium containing 3.0 to 300 pM proteoloytically active human α‐thrombin. After 12 hr in thrombin‐containing medium, 98% of the astrocytes had a flattened morphology. No flattening occured if α‐thrombin was replaced by γ‐thrombin, which has its fibrinogen‐recognition exosite disrupted. PNI added at 1 nM to serum‐containing medium caused stellation after 3 hr, and astroglia were 50% stellate by 12 hr. The effect of thrombin was mimicked by a 7‐amino acid peptide (TRP‐7) action on astrocytes. These results indicate that astrocytes possess a cell surface receptor for thrombin, similar to that described for platelets, endothelial cells, and neurons. © 1994 Wiley‐Liss, Inc.This article is a US Government work and, as such, is in the public

ISSN:0360-4012    

DOI:10.1002/jnr.490370115

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractWe report the loaclization of PDGFRα mRNA (PDGFRα) in phenotypically defined cells during the first postanatal week of rat forebrain development. Using a method of combined immunocytochemistry and in situ hybridization we have demonstrated the cellular colocalization of PDGFRα mRNA with GD3ganglioside or 04 sulfatide, phenotypic markers of oligodendrocytes, in the gray and white matter of the dorsal cerebral cortex at all ages studies. Population analysis of the PDGFRα+/G3+ and PDGFRα+/analysis of the PDGFRα+/GD3+and PDGFRα+/04+ cells revealed that three populations express PDGFRα: GD3+, GD3+/04+, and 04+, corresponding to two lineage stages, progenitor and preoligodendrocyte, in oligodendrocyte development. Immature oligodendrocytes, identifice by galactocerebroside immunoreactivity, did not express detectable levels of PDGFR α mRNA. Post‐mitotic neurons, identifice by immunoperodxidase localization of the 68 kD neurofilament, and astrocytes identified by S‐100 or GFAP immunoreactivity were also negative for PDGFRα mRNA occured in oligodendrocyte cell populations which are post‐migratory and proliferative, but which do not express myelin proteins characteristic of post‐mitotic oligodendrocytes. © 19

ISSN:0360-4012    

DOI:10.1002/jnr.490370116

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractNeuronal degeneration has been shown to be involved in various neurological disorders. Growth/trophic factors and their receptors are known to be important for the regeneration and survival of neurons. We report here the molecular cloning of a receptor‐like protein tyrosine kinase,bsk, (for brain specific kinase).Bskis highly related to theeph/elkreceptor like kinase family members. Northern blot analysis shows that is is expressed specifically in the brain, with no expression detected in adult heart, spleen, lung, liver, skeletal muscle, and kidney. In situ hybridization analysis of adult mouse brain sections indicates thatbskis expressed at high levels in the hippocampus, tenia tects, indusium griseum, and the piriform cortex, major components of the limbic system that are important for learning and memory. In addition, elevated levels of expression are found in other areas of the limbic system such as the amygdala, medial septum, and nucleus of the diagonal band, and in the olfactory bulb, which has close connections to the limbic system. The highest level of expression is found in the CA3 region of the hippocampus and the pyramidal cell layer of the piriform cortex. In 16.5 day mouse embryos,bskis expressed predominantly in the primordial cortex of the telencephalon. An antibody against a C‐terminal peptide ofbskrecognized a 105 kD protein in the 16.5 day embryonic head extract. Our analysis shows thatbskis a growth factor receptor‐like protein tyrosine kinase and that its greatest expression in the adult brain is associated with components of the limbic system. © 1994 Wiley‐L

ISSN:0360-4012    

DOI:10.1002/jnr.490370117

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractParkinson's disease is a prevalent neurological disease characterized by profound and incapacitating movement disorders. A common pathology in Parkinson's patients is degeneration of substantia nigra dopaminergic neurons that innervate the striatum and a corresponding decrease in striatal dopamine content. We now report that NT‐4/5 can prevent the death of rat embryonic substantia nigra dopaminergic neurons in low density, enriched, primary cultures. Furthermore, these neurons express messenger RNA encoding the trkB receptor for NT‐4/5 and transcripts for NT‐4/5 are present in their environment. In addition, we demonstrate that NT‐4/5 protects embryonic dopaminergic neurons from the toxic effects of the neurotoxin MPP+ THUAS, nt‐4/5 could be a physiological survival factor for midbrain dopaminergic neurons and may be useful as a therapeutic agent for parkinson's disease. © 1994 Wiley

ISSN:0360-4012    

DOI:10.1002/jnr.490370118

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

ISSN:0360-4012    

DOI:10.1002/jnr.490370102

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY