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Ibuprofen inhibits the synaptic failure induced by the amyloid-ß peptide in hippocampal neurons.
Zurita, Maria Paz; Muñoz, Gonzalo; Sepúlveda, Fernando J; Gómez, Paulina; Castillo, Carolina; Burgos, Carlos F; Fuentealba, Jorge; Opazo, Carlos; Aguayo, Luis G.
Affiliation
  • Zurita MP; Laboratory of Neurophysiology, Department of Physiology, Faculty of Biological Sciences, University of Concepción, Concepción, Chile.
J Alzheimers Dis ; 35(3): 463-73, 2013.
Article in En | MEDLINE | ID: mdl-23455989
ABSTRACT
Epidemiological studies have reported a decrease in the prevalence of Alzheimer's disease in individuals who chronically use non-steroidal anti-inflammatory drugs (NSAIDs). Clinical trials, on the other hand, have been less positive. Nevertheless, it has been proposed that NSAIDs exert part of their effects by reducing long-term cerebral neuroinflammation, although this mechanism has not been proven. In this study, we report that ibuprofen, one of the more widely used non-steroidal anti-inflammatory drugs, was able to alter the ultrastructure of amyloidpeptide (Aß) and significantly decrease its association to neuronal membranes, and consequently, its synaptotoxic effect in rat primary hippocampal and cortical cultures at 24 h incubation. In agreement with these results, we found that the decrease in the frequency of calcium transients with Aß was partly recovered by addition of ibuprofen (8.0 × 10-2 Hz in control; 3.4 × 10-2 Hz in 5 µM Aß, and 5.9 × 10-2 Hz in the presence of Aß and 200 µM ibuprofen). Additionally, this effect correlated well with the increment and recovery of miniature spontaneous currents (47 ± 5% of control in 1 µM Aß alone and 104 ± 14% in the presence of Aß and ibuprofen). Our results suggest that ibuprofen could be exerting its neuroprotective effect by directly interacting with Aß and altering its toxic aggregated forms. We postulate that other ibuprofen analogs with better pharmacological properties might have a higher efficacy in AD.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Serum Amyloid A Protein / Anti-Inflammatory Agents, Non-Steroidal / Ibuprofen / Synaptic Transmission / Neuroprotective Agents / Neurons Type of study: Risk_factors_studies Limits: Animals Language: En Journal: J Alzheimers Dis Journal subject: GERIATRIA / NEUROLOGIA Year: 2013 Document type: Article Affiliation country:

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Serum Amyloid A Protein / Anti-Inflammatory Agents, Non-Steroidal / Ibuprofen / Synaptic Transmission / Neuroprotective Agents / Neurons Type of study: Risk_factors_studies Limits: Animals Language: En Journal: J Alzheimers Dis Journal subject: GERIATRIA / NEUROLOGIA Year: 2013 Document type: Article Affiliation country: