CHF5074 is a non-steroidal anti-inflammatory derivative holding disease-modifying potential for thetreatment of Alzheimer’s disease. The aim of the present study was to characterize the electrophysio-logical and metabolic profile of CHF5074 in the hippocampus. Electrophysiological recordings show thatCHF5074 inhibits in a dose-dependent manner the current-evoked repetitive firing discharge in CA1 pyra-midal neurons. This result is paralleled by a dose-dependent reduction of field excitatory post-synapticpotentials with no effect on the paired-pulse ratio. The effects of CHF5074 were not mediated by AMPA orNMDA receptors, since the inward currents induced by local applications of AMPA and NMDA remainedconstant in the presence of this compound. We also suggest a possible activity of CHF5074 on ASIC1areceptor since ASIC1a-mediated current, evoked by application of a pH 5.5 solution, is reduced by pre-treatment with this compound. Moreover, we demonstrate that CHF5074 treatment is able to counteractin hippocampal slices the OGD-induced increase in alanine, lactate and acetate levels. Finally, CHF5074significantly reduced the apoptosis in hippocampal neurons exposed to OGD, as revealed by cleaved-caspase-3 immunoreactivity and TUNEL staining. Overall, the present work identifies novel mechanismsfor CHF5074 in reducing metabolic acidosis, rendering this compound potentially useful also in conditionsof brain ischemia.

Electrophysiological and metabolic effects of CHF5074 in the hippocampus : Protection against in vitro ischemia / D. Mango, G. Barbato, S. Piccirilli, M.B. Panico, M. Feligioni, C. Schepisi, M. Graziani, V. Porrini, M. Benarese, A. Lanzillotta, M. Pizzi, S. Pieraccini, M. Sironi, F. Blandini, F. Nicoletti, N.B. Mercuri, B.P. Imbimbo, R. Nisticò. - In: PHARMACOLOGICAL RESEARCH. - ISSN 1043-6618. - 81(2014), pp. 83-90.

Electrophysiological and metabolic effects of CHF5074 in the hippocampus : Protection against in vitro ischemia

S. Pieraccini;M. Sironi;
2014

Abstract

CHF5074 is a non-steroidal anti-inflammatory derivative holding disease-modifying potential for thetreatment of Alzheimer’s disease. The aim of the present study was to characterize the electrophysio-logical and metabolic profile of CHF5074 in the hippocampus. Electrophysiological recordings show thatCHF5074 inhibits in a dose-dependent manner the current-evoked repetitive firing discharge in CA1 pyra-midal neurons. This result is paralleled by a dose-dependent reduction of field excitatory post-synapticpotentials with no effect on the paired-pulse ratio. The effects of CHF5074 were not mediated by AMPA orNMDA receptors, since the inward currents induced by local applications of AMPA and NMDA remainedconstant in the presence of this compound. We also suggest a possible activity of CHF5074 on ASIC1areceptor since ASIC1a-mediated current, evoked by application of a pH 5.5 solution, is reduced by pre-treatment with this compound. Moreover, we demonstrate that CHF5074 treatment is able to counteractin hippocampal slices the OGD-induced increase in alanine, lactate and acetate levels. Finally, CHF5074significantly reduced the apoptosis in hippocampal neurons exposed to OGD, as revealed by cleaved-caspase-3 immunoreactivity and TUNEL staining. Overall, the present work identifies novel mechanismsfor CHF5074 in reducing metabolic acidosis, rendering this compound potentially useful also in conditionsof brain ischemia.
ASICs; CHF5074; Electrophysiology; Hippocampus; Neuroprotection
Settore BIO/15 - Biologia Farmaceutica
Settore CHIM/02 - Chimica Fisica
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/236722
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