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Atorvastatin and Fluoxetine Prevent Oxidative Stress and Mitochondrial Dysfunction Evoked by Glutamate Toxicity in Hippocampal Slices.
Mol Neurobiol. 2017 07; 54(5):3149-3161.MN

Abstract

Atorvastatin has been shown to exert a neuroprotective action by counteracting glutamatergic toxicity. Recently, we have shown atorvastatin also exerts an antidepressant-like effect that depends on both glutamatergic and serotonergic systems modulation. Excitotoxicity is involved in several brain disorders including depression; thus, it is suggested that antidepressants may target glutamatergic system as a final common pathway. In this study, a comparison of the mechanisms involved in the putative neuroprotective effect of a repetitive atorvastatin or fluoxetine treatment against glutamate toxicity in hippocampal slices was performed. Adult Swiss mice were treated with atorvastatin (10 mg/kg, p.o.) or fluoxetine (10 mg/kg, p.o.), once a day during seven consecutive days. On the eighth day, animals were killed and hippocampal slices were obtained and subjected to an in vitro protocol of glutamate toxicity. An acute treatment of atorvastatin or fluoxetine was not neuroprotective; however, the repeated atorvastatin or fluoxetine treatment prevented the decrease in cellular viability induced by glutamate in hippocampal slices. The loss of cellular viability induced by glutamate was accompanied by increased D-aspartate release, increased reactive oxygen species (ROS) and nitric oxide (NO) production, and impaired mitochondrial membrane potential. Atorvastatin or fluoxetine repeated treatment also presented an antidepressant-like effect in the tail suspension test. Atorvastatin or fluoxetine treatment was effective in protecting mice hippocampal slices from glutamate toxicity by preventing the oxidative stress and mitochondrial dysfunction.

Authors+Show Affiliations

Programa de Pós-graduação em Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade, 88040-900, Florianópolis, SC, Brazil. fabianakalyne@hotmail.com. Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade, 88040-900, Florianópolis, SC, Brazil. fabianakalyne@hotmail.com. Curso de Farmácia, Universidade do Contestado, 89460-000, Canoinhas, SC, Brazil. fabianakalyne@hotmail.com.Programa de Pós-graduação em Neurociências, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade, 88040-900, Florianópolis, SC, Brazil.Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade, 88040-900, Florianópolis, SC, Brazil.Programa de Pós-graduação em Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade, 88040-900, Florianópolis, SC, Brazil.Programa de Pós-graduação em Neurociências, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade, 88040-900, Florianópolis, SC, Brazil.Programa de Pós-graduação em Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade, 88040-900, Florianópolis, SC, Brazil. Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade, 88040-900, Florianópolis, SC, Brazil. Programa de Pós-graduação em Neurociências, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade, 88040-900, Florianópolis, SC, Brazil.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27052955

Citation

Ludka, Fabiana K., et al. "Atorvastatin and Fluoxetine Prevent Oxidative Stress and Mitochondrial Dysfunction Evoked By Glutamate Toxicity in Hippocampal Slices." Molecular Neurobiology, vol. 54, no. 5, 2017, pp. 3149-3161.
Ludka FK, Dal-Cim T, Binder LB, et al. Atorvastatin and Fluoxetine Prevent Oxidative Stress and Mitochondrial Dysfunction Evoked by Glutamate Toxicity in Hippocampal Slices. Mol Neurobiol. 2017;54(5):3149-3161.
Ludka, F. K., Dal-Cim, T., Binder, L. B., Constantino, L. C., Massari, C., & Tasca, C. I. (2017). Atorvastatin and Fluoxetine Prevent Oxidative Stress and Mitochondrial Dysfunction Evoked by Glutamate Toxicity in Hippocampal Slices. Molecular Neurobiology, 54(5), 3149-3161. https://doi.org/10.1007/s12035-016-9882-6
Ludka FK, et al. Atorvastatin and Fluoxetine Prevent Oxidative Stress and Mitochondrial Dysfunction Evoked By Glutamate Toxicity in Hippocampal Slices. Mol Neurobiol. 2017;54(5):3149-3161. PubMed PMID: 27052955.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Atorvastatin and Fluoxetine Prevent Oxidative Stress and Mitochondrial Dysfunction Evoked by Glutamate Toxicity in Hippocampal Slices. AU - Ludka,Fabiana K, AU - Dal-Cim,Tharine, AU - Binder,Luisa Bandeira, AU - Constantino,Leandra Celso, AU - Massari,Caio, AU - Tasca,Carla I, Y1 - 2016/04/06/ PY - 2015/12/26/received PY - 2016/03/21/accepted PY - 2016/4/8/pubmed PY - 2018/3/10/medline PY - 2016/4/8/entrez KW - Atorvastatin KW - Fluoxetine KW - Glutamate toxicity KW - Hippocampal slices KW - Neuroprotection SP - 3149 EP - 3161 JF - Molecular neurobiology JO - Mol Neurobiol VL - 54 IS - 5 N2 - Atorvastatin has been shown to exert a neuroprotective action by counteracting glutamatergic toxicity. Recently, we have shown atorvastatin also exerts an antidepressant-like effect that depends on both glutamatergic and serotonergic systems modulation. Excitotoxicity is involved in several brain disorders including depression; thus, it is suggested that antidepressants may target glutamatergic system as a final common pathway. In this study, a comparison of the mechanisms involved in the putative neuroprotective effect of a repetitive atorvastatin or fluoxetine treatment against glutamate toxicity in hippocampal slices was performed. Adult Swiss mice were treated with atorvastatin (10 mg/kg, p.o.) or fluoxetine (10 mg/kg, p.o.), once a day during seven consecutive days. On the eighth day, animals were killed and hippocampal slices were obtained and subjected to an in vitro protocol of glutamate toxicity. An acute treatment of atorvastatin or fluoxetine was not neuroprotective; however, the repeated atorvastatin or fluoxetine treatment prevented the decrease in cellular viability induced by glutamate in hippocampal slices. The loss of cellular viability induced by glutamate was accompanied by increased D-aspartate release, increased reactive oxygen species (ROS) and nitric oxide (NO) production, and impaired mitochondrial membrane potential. Atorvastatin or fluoxetine repeated treatment also presented an antidepressant-like effect in the tail suspension test. Atorvastatin or fluoxetine treatment was effective in protecting mice hippocampal slices from glutamate toxicity by preventing the oxidative stress and mitochondrial dysfunction. SN - 1559-1182 UR - https://www.unboundmedicine.com/medline/citation/27052955/Atorvastatin_and_Fluoxetine_Prevent_Oxidative_Stress_and_Mitochondrial_Dysfunction_Evoked_by_Glutamate_Toxicity_in_Hippocampal_Slices_ L2 - https://dx.doi.org/10.1007/s12035-016-9882-6 DB - PRIME DP - Unbound Medicine ER -