Riluzole promotes survival of rat motoneurons in vitro by stimulating trophic activity produced by spinal astrocyte monolayers

Peluffo, Hugo; Estévez, Álvaro G.; Barbeito, Luis; Stutzmann, Jean‐Marie

doi:10.1016/s0304-3940(97)00384-4

Cited by 58 publications

(56 citation statements)

References 24 publications

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“…At the same time, the evidence indicates that a soluble factor released by astrocytes in response to physiological concentrations of 17b-estradiol was likely involved. Riluzole slows the progression and symptoms of ALS [Bensimon et al, 1994], and it has been demonstrated to promote motor neuron survival also by stimulating the production of trophic factors by astrocytes [Peluffo et al, 1997;Mizuta et al, 2001]. As possible candidates, insulin-like growth factor I (IGF-I) and vascular endothelial growth factor (VEGF) have been shown to antagonize motor neuron degeneration [Van Den Bosch et al, 2004;Vincent et al, 2004].…”

Section: Amyotrophic Lateral Sclerosis (Als)mentioning

confidence: 99%

A major role for astrocytes in the neuroprotective effect of estrogen

Sortino

Platania

Chisari

et al. 2005

Drug Development Research

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Estrogen exerts neurotrophic and neuroprotective activity as suggested by both in vitro and in vivo evidence. Expression of estrogen receptors has been demonstrated in neurons and also in glial cells. Glia, and in particular astrocytes, represent a target for estrogen and contribute to the neuroprotective effect of the steroid hormone. Particular emphasis is given here to the role of astrocytes in mediating some of the protective effects of estrogen in models of neuronal damage. Estrogen receptors are up-regulated in different brain areas during neurodegeneration, a phenomenon that may potentiate neuroprotective mechanisms, and estrogen appears effective in modulating the uptake of the excitotoxin glutamate. In addition, following neuronal insults, astrocytes may represent a source of estrogen through overexpression of the estrogen-synthesizing enzyme, aromatase. The contribution of astrocytes as a source of growth factors is also discussed in terms of the neuroprotection obtained in different in vitro models of neurodegenerative conditions. Drug Dev. Res. 66:126-135, 2006.

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Section: Amyotrophic Lateral Sclerosis (Als)mentioning

confidence: 99%

A major role for astrocytes in the neuroprotective effect of estrogen

Sortino

Platania

Chisari

et al. 2005

Drug Development Research

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“…In its dual neuroprotective [45] and neurotoxic actions (this study), riluzole seems to belong to a class of compounds that elicit neuroprotection at their lower concentrations; however, at their higher concentrations the neuroprotection diminishes or even disappears, as the case is for compounds derived from the glutamic acid moiety [46]. This dual action has also been found with galantamine and donepezil [47,48], two drugs that are being clinically used to treat Alzheimer's disease [49].…”

Section: Discussionmentioning

confidence: 99%

“…For instance, riluzole has been shown to distort the intracellular Ca 2+ homeostasis [50,51,52]; this may be linked to its reported apoptotic and cytotoxic effects in human prostate cancer cells [53] and in Madin-Darby canine kidney cells [52]. On the opposite side are the findings that riluzole regulates the expression of neurotrophic factor genes in C6 glioma cells [54], stimulates the synthesis of nerve growth factor and brain-derived neurotrophic factor in cultured mouse astrocytes [55], and augments brain-derived neurotrophic factor production with consequent proliferation of granule precursor cells in the rat hippocampus [56] and promotion of survival of rat MCNs through stimulation of trophic activity produced by spinal astrocyte monolayers [45]. These paradoxical and complex responses suggest that riluzole could exert different neuroprotective or neurotoxic actions by activating different signalling pathways at lower or higher concentrations.…”

Section: Discussionmentioning

confidence: 99%

The Neuroprotection Exerted by Memantine, Minocycline and Lithium, against Neurotoxicity of CSF from Patients with Amyotrophic Lateral Sclerosis, Is Antagonized by Riluzole

Yáñez¹,

Matías‐Guiu²,

Arranz-Tagarro³

et al. 2013

Neurodegener Dis

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In a recent study we found that cerebrospinal fluids (CSFs) from amyotrophic lateral sclerosis (ALS) patients caused 20-30% loss of cell viability in primary cultures of rat embryo motor cortex neurons. We also found that the antioxidant resveratrol protected against such damaging effects and that, surprisingly, riluzole antagonized its protecting effects. Here we have extended this study to the interactions of riluzole with 3 other recognized neuroprotective agents, namely memantine, minocycline and lithium. We found: (1) by itself riluzole exerted neurotoxic effects at concentrations of 3-30 µM; this cell damage was similar to that elicited by 30 µM glutamate and a 10% dilution of ALS/CSF; (2) memantine (0.1-30 µM), minocycline (0.03-1 µM) and lithium (1-80 µg/ml) afforded 10-30% protection against ALS/CSF-elicited neurotoxicity, and (3) at 1-10 µM, riluzole antagonized the protection afforded by the 3 agents. These results strongly support the view that at the riluzole concentrations reached in the brain of patients, the neurotoxic effects of this drug could be masking the potential neuroprotective actions of new compounds being tested in clinical trials. Therefore, in the light of the present results, the inclusion of a group of patients free of riluzole treatment may be mandatory in future clinical trials performed in ALS patients with novel neuroprotective compounds.

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“…It had also demonstrated that it produced a marked increase in the striatal glial fibrillary acidic protein (GFAP) [27]. And riluzole may stimulate the production of trophic activities for motoneurons by spinal astrocyte cultures [28].…”

Section: Discussionmentioning

confidence: 99%

G0/G1 Phase Arrest and Apoptosis Induced by Manganese Chloride on Cultured Rat Astrocytes and Protective Effects of Riluzole

Deng

et al. 2011

Biol Trace Elem Res

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Occupational or environmental exposure to excessive Mn would cause manganism, which is resembled Parkinson disease. However, the mechanism underlying manganism is still unknown. It had been documented that astrocytes play important roles in physiological function in brain. Therefore, in the present study, the cultured astrocytes were exposed to 0, 125, 250, and 500 μM MnCl(2), and cell viability, lactate dehydrogenase (LDH) leakage, morphological change, cell cycle progression, and apoptosis were determined. In addition, 100 μM riluzole (a glutamatergic modulator) was pretreated for 6 h before no MnCl(2) exposure or 500 μM MnCl(2) exposure. The results showed that cell viability inhibited, LDH leakage elevated, morphology injured, G(0)/G(1) phase cell cycle arrested, and apoptosis rate increased in a concentration-dependent manner. Further investigation indicated that riluzole pretreatment reversed cytotoxicity, cell cycle aberration, and apoptosis on astrocytes caused by MnCl(2). These results suggested that MnCl(2) could cause cytotoxicity, cell cycle arrest, and apoptosis concentration-dependently; riluzole might antagonize Mn toxicity on astrocytes.

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Riluzole promotes survival of rat motoneurons in vitro by stimulating trophic activity produced by spinal astrocyte monolayers

Cited by 58 publications

References 24 publications

A major role for astrocytes in the neuroprotective effect of estrogen

A major role for astrocytes in the neuroprotective effect of estrogen

The Neuroprotection Exerted by Memantine, Minocycline and Lithium, against Neurotoxicity of CSF from Patients with Amyotrophic Lateral Sclerosis, Is Antagonized by Riluzole

G0/G1 Phase Arrest and Apoptosis Induced by Manganese Chloride on Cultured Rat Astrocytes and Protective Effects of Riluzole

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