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Biomedical subjects

P Sindou

Publications and source records attributed to P Sindou.

28 records · Page 2Linked to original sources
PubMed1994

Neuroprotective effects of riluzole in ALS CSF toxicity.

Amyotrophic lateral sclerosis (ALS) is a neurological disorder neuropathologically characterized by a progressive degeneration of upper and lower motoneurons. The origin of the neuronal death is presently unknown but recent findings suggest that neurodegeneration could be related to an excitotoxic disorder. We have recently shown that the cerebrospinal fluid (CSF) of ALS patients contains for neurones in cultures cytotoxic factors whose toxic properties are mediated by AMPA/kainate receptors, a subgroup of glutamate post-synaptic receptors. This study reports that riluzole partially prevents in vitro the neuronal degeneration produced by ALS CSF (neuronal survival 60.6 +/- 13.1%). Riluzole (5 x 10(-7) M) which reduces excitatory amino acid release, could represent a new pharmacological agent susceptible to be proposed to patients affected by this dramatic neurological disease.

Amyotrophic Lateral Sclerosis↗
PubMed1994

Tetrodotoxin blocks HIV coat protein (gp120) toxicity in primary neuronal cultures.

HIV-1-associated cognitive/motor complex is a frequent neurological complication of the acquired immunodeficiency syndrome (AIDS). The pathogenesis of this syndrome implicates immunopathological and toxic events such as the production of cytokines. The HIV envelope glycoprotein gp120 seems also to play a major role in this process. Gp120 could produce a slow neuronal death probably via the release of neurotoxic factors by CNS macrophages/monocytes. NMDA antagonists and Ca2+ channel blockers in vitro have a powerful neuroprotective effect against gp120 neurotoxicity. The purpose of the present work is to determine whether gp120-induced neurotoxicity is associated with an abnormal neuronal depolarization induced by putative neurotoxins. We have compared in vitro the neuroprotective effects of Tetrodotoxin a Na+ channel blocker, the Ca2+ channel blocker nifedipine and the NMDA antagonist MK-801 in primary cortical neurons taken from embryonic rat and intoxicated with gp120. We observed comparable neuroprotective effects with the 3 precited compounds suggesting that gp120-induced neurotoxic factors act on Na+ channels, NMDA receptors and Ca2+ channels in a cascade of cellular events. We confirmed that the presence of macrophages is needed to trigger a marked gp120-induced neurotoxicity. These results underline the fact that depolarization is an important component of gp120 neurotoxicity in primary neuronal cultures.

Animals↗
PubMed1994

Prevention of HIV coat protein (gp120) toxicity in cortical cell cultures by riluzole.

Neurological complications observed in HIV-infected patients are very frequent. Neocortical lesions include reduced neuronal density due to neuronal degeneration. The HIV envelope protein gp120 has potent neurotoxic properties in cell cultures blocked either by NMDA antagonists or calcium channel antagonists. Moreover, human monocytoid cell lines infected by HIV release endogenous toxic factors with comparable cellular actions. We have analysed the effects of riluzole, a compound reducing the excitatory amino acid release on gp120-induced neurotoxicity in primary neuronal cultures. Riluzole, which blocks the release of glutamate and aspartate from nerve terminals, prevents (10(-7) M) the neuronal degeneration produced by 20 pM of gp120 in cortical cell cultures. This result could suggest that toxic factors produced by activated macrophages might increase glutamate release, and that this may be prevented by riluzole.

Animals↗
PubMed1994

Synaptophysin expression during in vitro neuronal differentiation. An immunocytochemical and a confocal laser microscopic study.

Primary neuronal cultures from mammalian fetal brains are widely used for morphological, biochemical and pharmacotoxicological studies. The usefulness of relatively pure neuronal cultures are now demonstrated for such studies. We have compared the neuronal survival and differentiation, the synaptophysin expression and the glial cell percentage in primary neuronal cultures using two different media: a M1 medium containing 10 % fetal calf serum and a M2 medium supplemented with hormones, ions and chemicals. Our study demonstrates that the M2 medium (a serum-free defined medium) is associated with an increased survival at 14 days of culture, an earlier neuronal differentiation and synaptophysin expression in cell bodies and neurites as it was confirmed by immunocytochemical and confocal laser microscopic studies.

Animals↗
PubMed1993

Cell culture evidence for neuronal degeneration in amyotrophic lateral sclerosis being linked to glutamate AMPA/kainate receptors.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting motor neurons. Glutamate, a potent central-nervous-system toxin, has been proposed as one possible factor in this motoneuron disease. Serum from patients with ALS is known to be toxic when added to neurons in culture. We report on the toxicity to rat neurons in culture of cerebrospinal fluid (CSF) from patients with ALS. CSF were obtained from 10 ALS patients, 10 neurological controls, and 10 other controls. ALS CSF was added at dilutions of 50%, 20%, or 10% and neuron survival was assessed after 24 h. The neuroprotective effects of antagonists to two glutamate receptors were also assessed. ALS CSF was significantly neurotoxic, with a neuronal survival rate of only 47% compared with 80% or so for control CSF. This neurotoxicity was blocked by CNQX, an antagonist to the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)/kainate receptor but not by two N-methyl-D-aspartate (NMDA) antagonists. ALS CSF contains a specific neurotoxic factor which is AMPA/kainate-like which could have a role in the neuronal degeneration of this disease.

2-Amino-5-phosphonovalerate↗
PubMed1993

[Antigenic changes of Tau protein induced by glutamate on primary cultures of neurons: immunocytochemistry study].

Degenerating neurons in Alzheimer's disease are characterized by the presence of neurofibrillary tangles constituted by paired helical filaments (PHF). Abnormally phosphorylated Tau protein, a microtubule associated protein is one of the major component of PHF. Abnormal phosphorylation seems to be located in the C-terminal domain but also in the N-terminal region of Tau proteins. Previous studies demonstrated that calcium-mediated glutamate toxicity produces a dose-dependent increase of Tau immunolabellings in neuronal cultures. Biochemical results revealed that these changes could be associated with abnormal Tau migrations on immunoblots. Using three anti-Tau antibodies the present study shows that glutamate toxicity induces in neuronal cultures, Tau modifications localized in the N- and C-terminal domains of the protein. These findings suggest the possibility that glutamate toxicity can induce Tau antigenic changes involving probably the whole molecule.

Animals↗
PubMed1992

Tau antigenic changes induced by glutamate in rat primary culture model: a biochemical approach.

Primary neuronal cultures were treated with glutamate to induce an increase of Tau immunoreactivity similar to that observed in Alzheimer's disease. The Tau profile of neurones in culture before and after exposure to glutamate was analyzed on immunoblots with anti-Tau, anti-paired helical filaments (PHF) and antibody specific for modified Tau. Differences were observed between treated and control cultures: glutamate induced a shift of immunodetection from the lowest to the highest molecular weight Tau isoform and an acidification of Tau proteins. However, these modifications are not exactly those observed in Alzheimer's disease since we were not able to detect 'Alzheimer-type' epitopes on Tau proteins after the glutamate exposure.

Alzheimer Disease↗
PubMed1992

A dose-dependent increase of Tau immunostaining is produced by glutamate toxicity in primary neuronal cultures.

Neuronal degeneration was produced in primary cultures by glutamate exposure and the modifications of Tau immunoreactivity were analysed in degenerating neurons. After 8-12 days of culture, glutamate was applied at different concentrations (50, 100, 200 and 500 mumol) in a Na(+)- and Mg(2+)-free solution containing calcium. Prior to and 12 hours after glutamate exposure cell death was defined by cell counting in each dish. After fixation, neurons were processed for immunocytochemistry using a Tau2 monoclonal antibody and a Tau polyclonal antibody (Sigma). Tau immunostaining was scored by a blind count of immunoreactive cells and a semi-quantitative evaluation. The results show that the number of labelled neurons and the magnitude of neuronal immunolabelling are both related to the glutamate concentration. Our findings indicate that glutamate induces a dose-dependent increase of Tau immunoreactivity directly related to its cellular action on neuronal cells.

Alzheimer Disease↗
PubMed1991

Survival of snails and characteristic lesions of Fasciola hepatica infection in four European species of Lymnaea.

The survival of snails and characteristic organ lesions were investigated in four different age categories (new-born, 1 and 2 mm shell height, adults) and in four species of Lymnaea (L. glabra, L. palustris, L. peregra ovata, L. truncatula) infected by Fasciola hepatica. Mortalities were higher in infected groups on Days 30 and 45 post-infection (+42% and +45%, respectively) than in controls. Lesions depended on the species and age of the Lymnaea. Epithelial necrosis of the kidney was recorded in L. glabra, L. palustris and L. p. ovata, whereas intralamellar deposits were found in the same organ of L. truncatula. All categories of L. truncatula had evolutive infections (snails with living parthenitae); the young snails of other species became infected, but the adults did not, as estimated at Day 45 post-infection. The lesions were related to the intensity of evolutive infections: necrosis of the digestive gland was found in moderate to low infections and, conversely, gonadal atrophy with epithelial necrosis was found in highly infected snails.

Animals↗