CSF from amyotrophic lateral sclerosis patients produces glutamate independent death of rat motor brain cortical neurons: Protection by resveratrol but not riluzole

Yáñez, Matilde; Galán, Lucía; Matías‐Guiu, Jorge; Vela, A.; Guerrero, Antonio; Garcı́a, Antonio G.

doi:10.1016/j.brainres.2011.09.025

Cited by 55 publications

(52 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…After 24 h incubation in this medium, the neuronal viability decreased in a range of 15-30% with ALS/CSF from different patients, a figure similar to that recently reported by our laboratories [29]. Because of this variability in the extent of ALS/CSF-elicited toxicity, in each individual experiment we normalized this value to 100% and calculated the protection exerted by a given compound as the fraction of recovery of neuronal viability (percent protection in the ordinates of fig.…”

Section: Resultssupporting

confidence: 78%

“…We followed the optimized protocol used to monitor the neurotoxic effects of individual ALS/CSF from each patient, diluted in neurobasal medium to the final concentration of 10% [29]. After 24 h incubation in this medium, the neuronal viability decreased in a range of 15-30% with ALS/CSF from different patients, a figure similar to that recently reported by our laboratories [29].…”

Section: Resultssupporting

confidence: 59%

“…1a) that compares well with the neuronal loss elicited by riluzole also at 30 µ M (28 ± 7.6%). At the 10% dilution used in our previous study [29], ALS/CSF produced 19.8 ± 2.6% neuronal loss (fig. 1a).…”

Section: Resultsmentioning

confidence: 99%

“…We also found that the polyphenolic anti-oxidant resveratrol [28] afforded protection against ALS/CSF toxicity but riluzole did not. Surprisingly, we also observed that when MCNs were incubated with both compounds, riluzole antagonized the neuroprotective effects of resveratrol [29]. Thus, the question arises whether this negative interaction is specific for riluzole and resveratrol or if it extends to other neuroprotective compounds such as memantine, minocycline and lithium, referred to above.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Resultssupporting

confidence: 78%

Section: Resultssupporting

confidence: 59%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Self Cite

View full text Add to dashboard Cite

show abstract

“…In this sense, resveratrol has been also reported to exert neuroprotection on in vitro models of ALS. Thus, Kim et al [26] showed that resveratrol reduces cell death on primary cultures of neurons overexpressing the SOD1 G93A mutant protein, and Yáñez et al [52] demonstrated that this compound protects from neuronal death triggered by CSF of ALS patients. There is some controversy about the in vivo effect of resveratrol administration in SOD1 G93A mice.…”

Section: Discussionmentioning

confidence: 99%

Resveratrol Improves Motoneuron Function and Extends Survival in SOD1G93A ALS Mice

et al. 2014

View full text Add to dashboard Cite

Amyotrophic lateral sclerosis (ALS) is an adult onset neurodegenerative disease that causes progressive paralysis and death due to degeneration of motoneurons in spinal cord, brainstem and motor cortex. Nowadays, there is no effective therapy and patients die 2-5 years after diagnosis. Resveratrol (trans-3,4′,5-trihydroxystilbene) is a natural polyphenol found in grapes, with promising neuroprotective effects since it induces expression and activation of several neuroprotective pathways involving Sirtuin1 and AMPK. The objective of this work was to assess the effect of resveratrol administration on SOD1 G93A ALS mice. We determined the onset of symptoms by rotarod test and evaluated upper and lower motoneuron function using electrophysiological tests.We assessed the survival of the animals and determined the number of spinal motoneurons. Finally, we further investigated resveratrol mechanism of action by means of western blot and immunohistochemical analysis. Resveratrol treatment from 8 weeks of age significantly delayed disease onset and preserved lower and upper motoneuron function in female and male animals. Moreover, resveratrol significantly extended SOD1 G93A mice lifespan and promoted survival of spinal motoneurons. Delayed resveratrol administration from 12 weeks of age also improved spinal motoneuron function preservation and survival. Further experiments revealed that resveratrol protective effects were associated with increased expression and activation of Sirtuin 1 and AMPK in the ventral spinal cord. Both mediators promoted normalization of the autophagic flux and, more importantly, increased mitochondrial biogenesis in the SOD1 G93A spinal cord. Taken together, our findings suggest that resveratrol may represent a promising therapy for ALS.

show abstract

Therapeutic potential of stilbenes in neuropsychiatric and neurological disorders: A comprehensive review of preclinical and clinical evidence

Socała,

Żmudzka,

Lustyk

et al. 2024

Phytotherapy Research

View full text Add to dashboard Cite

Neuropsychiatric disorders are anticipated to be a leading health concern in the near future, emphasizing an outstanding need for the development of new effective therapeutics to treat them. Stilbenes, with resveratrol attracting the most attention, are an example of multi‐target compounds with promising therapeutic potential for a broad array of neuropsychiatric and neurological conditions. This review is a comprehensive summary of the current state of research on stilbenes in several neuropsychiatric and neurological disorders such as depression, anxiety, schizophrenia, autism spectrum disorders, epilepsy, traumatic brain injury, and neurodegenerative disorders. We describe and discuss the results of both in vitro and in vivo studies. The majority of studies concentrate on resveratrol, with limited findings exploring other stilbenes such as pterostilbene, piceatannol, polydatin, tetrahydroxystilbene glucoside, or synthetic resveratrol derivatives. Overall, although extensive preclinical studies show the potential benefits of stilbenes in various central nervous system disorders, clinical evidence on their therapeutic efficacy is largely missing.

show abstract

CSF from amyotrophic lateral sclerosis patients produces glutamate independent death of rat motor brain cortical neurons: Protection by resveratrol but not riluzole

Cited by 55 publications

References 48 publications

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

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

Resveratrol Improves Motoneuron Function and Extends Survival in SOD1G93A ALS Mice

Therapeutic potential of stilbenes in neuropsychiatric and neurological disorders: A comprehensive review of preclinical and clinical evidence

Contact Info

Product

Resources

About