CHF5074 and LY450139 sub-acute treatments differently affect cortical extracellular glutamate levels in pre-plaque Tg2576 mice

• Published in: Neuroscience 2014-04, Vol.266, p.13-22
• Main Authors: Beggiato, S, Giuliani, A, Sivilia, S, Lorenzini, L, Antonelli, T, Imbimbo, B.P, Giardino, L, Calzà, L, Ferraro, L
• Format: Article
• Language: English
• Subjects: Alanine - analogs & derivatives; Alanine - pharmacology; Alzheimer Disease - metabolism; Alzheimer’s disease; Animals; Azepines - pharmacology; Cyclopropanes - pharmacology; Disease Models, Animal; Extracellular Space - chemistry; Female; Flurbiprofen - analogs & derivatives; Flurbiprofen - pharmacology; Glutamic Acid - metabolism; Humans; in vivo microdialysis; Mice; Mice, Transgenic; Microdialysis; Neurology; Neuroprotective Agents - pharmacology; novel object recognition and contextual fear conditioning; Prefrontal Cortex - drug effects; Prefrontal Cortex - metabolism; Synaptic Transmission - drug effects; β-amyloid targeting drugs; γ-secretase
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2014.01.065

Graphical abstract CHF5074 is a nonsteroidal anti-inflammatory derivative that has been shown to inhibit β-amyloid plaque deposition and to reverse memory deficit in vivo in transgenic mouse models of Alzheimer’s disease. In the present in vivo study we used pre-plaque Tg2576 mice to investigate the effects of a sub-acute treatment with CHF5074 or LY450139 (a potent γ-secretase inhibitor) on prefrontal cortex dialysate glutamate levels. The injection of CHF5074 reduced, while LY450139 increased, prefrontal cortex dialysate glutamate levels in Tg2576 mice, but not in wild-type animals. These results suggest that at the dose tested CHF5074 and LY450139 differently affect cortical glutamate transmission in pre-plaque Tg2576 mice. This different neurochemical profile could be involved in the different ability of the two drugs in improving early cognitive performance in this animal model of Alzheimer’s disease.