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

First Author  Beggiato S Year  2014
Journal  Neuroscience Volume  266
Pages  13-22 PubMed ID  24530449
Mgi Jnum  J:210338 Mgi Id  MGI:5570508
Doi  10.1016/j.neuroscience.2014.01.065 Citation  Beggiato S, et al. (2014) CHF5074 and LY450139 sub-acute treatments differently affect cortical extracellular glutamate levels in pre-plaque Tg2576 mice. Neuroscience 266:13-22
abstractText  CHF5074 is a nonsteroidal anti-inflammatory derivative that has been shown to inhibit beta-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 gamma-secretase inhibitor, that has been shown to inhibit brain beta-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.
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