title: CHF5074 and LY450139 sub-acute treatments differently affect cortical extracellular glutamate levels in pre-plaque Tg2576 mice.
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 (AD). In the present in vivo study we used pre-plaque Tg2576 mice showing cognitive impairments to investigate the effects of a sub-acute treatment with CHF5074 on prefrontal cortex dialysate glutamate levels. Furthermore, the effects of CHF5074 have been compared with those induced, under the same experimental conditions, by LY450139, a potent γ-secretase inhibitor, that has been shown to inhibit brain β-amyloid production. No differences in prefrontal cortex dialysate glutamate levels were observed between control Tg2576 and wild-type animals. A sub-acute (8days) treatment with CHF5074 (30mg/kg, s.c.), LY450139 (3mg/kg, s.c.) or their respective vehicles did not modify prefrontal cortex dialysate glutamate levels. After these treatments, 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 AD.
authors: Department of Medical Sciences, University of Ferrara, Via Fossato di Mortara 17-19, 44121 Ferrara, Italy.
authors: S
authors: S
authors: Beggiato
authors: Department of Veterinary Medical Sciences, University of Bologna, Via Tolara di Sopra 50, 40064 Ozzano Emilia, Bologna, Italy.
authors: A
authors: A
authors: Giuliani
authors: Department of Veterinary Medical Sciences, University of Bologna, Via Tolara di Sopra 50, 40064 Ozzano Emilia, Bologna, Italy.
authors: S
authors: S
authors: Sivilia
authors: Health Science and Technologies, Interdepartmental Center for Industrial Research (HST-ICIR), University of Bologna, Via Tolara di Sopra 41/E, 40064 Ozzano Emilia, Bologna, Italy.
authors: L
authors: L
authors: Lorenzini
authors: Department of Medical Sciences, University of Ferrara, Via Fossato di Mortara 17-19, 44121 Ferrara, Italy; IRET Foundation, Via Tolara di Sopra 41/E, 40064 Ozzano Emilia, Bologna, Italy.
authors: T
authors: T
authors: Antonelli
authors: Research & Development, Chiesi Farmaceutici, Via Palermo 26/A, 43100 Parma, Italy.
authors: B P
authors: BP
authors: Imbimbo
authors: Department of Veterinary Medical Sciences, University of Bologna, Via Tolara di Sopra 50, 40064 Ozzano Emilia, Bologna, Italy; Health Science and Technologies, Interdepartmental Center for Industrial Research (HST-ICIR), University of Bologna, Via Tolara di Sopra 41/E, 40064 Ozzano Emilia, Bologna, Italy; IRET Foundation, Via Tolara di Sopra 41/E, 40064 Ozzano Emilia, Bologna, Italy.
authors: L
authors: L
authors: Giardino
authors: Department of Veterinary Medical Sciences, University of Bologna, Via Tolara di Sopra 50, 40064 Ozzano Emilia, Bologna, Italy; Health Science and Technologies, Interdepartmental Center for Industrial Research (HST-ICIR), University of Bologna, Via Tolara di Sopra 41/E, 40064 Ozzano Emilia, Bologna, Italy; IRET Foundation, Via Tolara di Sopra 41/E, 40064 Ozzano Emilia, Bologna, Italy.
authors: L
authors: L
authors: Calzà
authors: IRET Foundation, Via Tolara di Sopra 41/E, 40064 Ozzano Emilia, Bologna, Italy; Department of Life Sciences and Biotechnology, University of Ferrara, Via L. Borsari 46, 44121 Ferrara, Italy. Electronic address: frl@unife.it.
authors: L
authors: L
authors: Ferraro
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D003521:Cyclopropanes / Q000494:pharmacology*; D004195:Disease Models, Animal; D005110:Extracellular Space / Q000737:chemistry; D005260:Female; D005480:Flurbiprofen / Q000031:analogs & derivatives* / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D017551:Microdialysis; D018696:Neuroprotective Agents / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects*
chemical_list: C522246:1-(3',4'-dichloro-2-fluoro(1,1'-biphenyl)-4-yl)cyclopropanecarboxylic acid; D001381:Azepines; D003521:Cyclopropanes; C484278:N2-((2S)-2-(3,5-difluorophenyl)-2-hydroxyethanoyl)-N1-((7S)-5-methyl-6-oxo-6,7-dihydro-5H-dibenzo(b,d)azepin-7-yl)-L-alaninamide; D018696:Neuroprotective Agents; D018698:Glutamic Acid; D005480:Flurbiprofen; D000409:Alanine
keywords: Alzheimer’s disease; in vivo microdialysis; novel object recognition and contextual fear conditioning; β-amyloid targeting drugs; γ-secretase