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Astroglial Proliferation (astroglial + proliferation)

Distribution by Scientific Domains
Life Sciences75%

Selected Abstracts

Differentiation and migration of astrocytes in the spinal cord following dorsal root injury in the adult rat

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2003
Elena N. Kozlova
Abstract Nerve fibre degeneration in the spinal cord is accompanied by astroglial proliferation. It is not known whether these cells proliferate in situ or are recruited from specific regions harbouring astroglial precursors. We found cells expressing nestin, characteristic of astroglial precursors, at the dorsal surface of the spinal cord on the operated side from 30 h after dorsal root injury. Nestin-expressing cells dispersed to deeper areas of the dorsal funiculus and dorsal horn on the operated side during the first few days after injury. Injection of bromodeoxyuridine (BrdU) 2 h before the end of the experiment, at 30 h after injury, revealed numerous BrdU-labelled, nestin-positive cells in the dorsal superficial region. In animals surviving 20 h after BrdU injection at 28 h postlesion, cells double-labelled with BrdU and nestin were also found in deeper areas. Labeling with BrdU 2 h before perfusion showed proliferation of microglia and radial astrocytes in the ventral and lateral funiculi on both sides of the spinal cord 30 h after injury. Nestin-positive cells coexpressed the calcium-binding protein Mts1, a marker for white matter astrocytes, in the dorsal funiculus, and were positive for glial fibrillary acidic protein (GFAP), but negative for Mts1 in the dorsal horn. One week after injury the level of nestin expression decreased and was undetectable after 3 months. Taken together, our data indicate that after dorsal root injury newly formed astrocytes in the degenerating white and grey matter first appear at the dorsal surface of the spinal cord from where some of them subsequently migrate ventrally, and differentiate into white- or grey-matter astrocytes. [source]

Functions and pathophysiological roles of phospholipase D in the brain

JOURNAL OF NEUROCHEMISTRY, Issue 6 2005
Jochen Klein
Abstract Ten years after the isoforms of mammalian phospholipase D (PLD), PLD1 and 2, were cloned, their roles in the brain remain speculative but several lines of evidence now implicate these enzymes in basic cell functions such as vesicular trafficking as well as in brain development. Many mitogenic factors, including neurotransmitters and growth factors, activate PLD in neurons and astrocytes. Activation of PLD downstream of protein kinase C seems to be a required step for astroglial proliferation. The characteristic disruption of the PLD signaling pathway by ethanol probably contributes to the delay of brain growth in fetal alcohol syndrome. The post-natal increase of PLD activities concurs with synapto- and myelinogenesis in the brain and PLD is apparently involved in neurite formation. In the adult and aging brain, PLD activity has antiapoptotic properties suppressing ceramide formation. Increased PLD activities in acute and chronic neurodegeneration as well as in inflammatory processes are evidently due to astrogliosis and may be associated with protective responses of tissue repair and remodeling. ARF-regulated PLD participates in receptor endocytosis as well as in exocytosis of neurotransmitters where PLD seems to favor vesicle fusion by modifications of the shape and charge of lipid membranes. Finally, PLD activities contribute free choline for the synthesis of acetylcholine in the brain. Novel tools such as RNA interference should help to further elucidate the roles of PLD isoforms in brain physiology and pathology. [source]

Mitogenic effects of phospholipase D and phosphatidic acid in transiently permeabilized astrocytes: effects of ethanol

JOURNAL OF NEUROCHEMISTRY, Issue 1 2003
Beate Schatter
Abstract Investigations of lipid-mediated signalling pathways are often limited by a lack of methods for the intracellular delivery of lipid messengers. We established a procedure for the transient permeabilization of astrocytes by an oxygen-insensitive mutant of streptolysin-O (SLO) to investigate the participation of the phospholipase D (PLD) signalling pathway in astroglial cell proliferation. Exogenous PLD, when incubated in the presence of SLO, caused an increase in DNA synthesis (measured by thymidine incorporation) which was completely suppressed by ethanol (0.3%, v/v). In parallel experiments, phosphatidic acid also induced a dose-dependent mitogenic response which, however, was not affected by the presence of ethanol. Phosphatidic acid was more effective in this assay than diacylglycerol but its effect was sensitive to the protein kinase inhibitor Ro 31-8220. Our findings provide direct evidence that disruption of the PLD signalling pathway by ethanol is sufficient to suppress astroglial proliferation, an effect that might contribute to the inhibition of brain growth in alcoholic embryopathy. [source]

Neuroprotective effects of zonisamide target astrocyte

ANNALS OF NEUROLOGY, Issue 2 2010
Masato Asanuma MD
Objective Recent double-blind, controlled trials in Japan showed that the antiepileptic agent zonisamide (ZNS) improves the cardinal symptoms of Parkinson's disease. Glutathione (GSH) exerts antioxidative activity through quenching reactive oxygen species and dopamine quinone. GSH depletion within dopaminergic neurons impairs mitochondrial complex I activity, followed by age-dependent nigrostriatal neurodegeneration. This study examined changes in GSH and GSH synthesis-related molecules, and the neuroprotective effects of ZNS on dopaminergic neurodegeneration using 6-hydroxydopamine,injected hemiparkinsonian mice brain and cultured neurons or astrocytes. Methods and Results ZNS increased both the cell number and GSH levels in astroglial C6 cells, but not in dopaminergic neuronal CATH.a cells. Repeated injections of ZNS (30mg/kg intraperitoneally) for 14 days also significantly increased GSH levels and S100,-positive astrocytes in mouse basal ganglia. Repeated ZNS injections (30mg/kg) for 7 days in the hemiparkinsonian mice increased the expression of cystine/glutamate exchange transporter xCT in activated astrocytes, which supply cysteine to neurons for GSH synthesis. Treatment of these mice with ZNS also increased GSH levels and completely suppressed striatal levodopa,induced quinone formation. Reduction of nigrostriatal dopamine neurons in the lesioned side of hemiparkinsonian mice was significantly abrogated by repeated injections of ZNS with or without adjunctive levodopa starting 3 weeks after 6-hydroxydopamine lesioning. Interpretation These results provide new pharmacological evidence for the effects of ZNS. ZNS markedly increased GSH levels by enhancing the astroglial cystine transport system and/or astroglial proliferation via S100, production or secretion. ZNS acts as a neuroprotectant against oxidative stress and progressive dopaminergic neurodegeneration. ANN NEUROL 2010;67:239,249 [source]