Deficits in glutamate neurotransmission and mitochondrial functions were detected in the frontal cortex (FC) and hippopcampus (HIPP) of aged 3 X Tg-Alzheimer's disease (AD) mice, compared with their wild type littermates (non-Tg). In particular, basal levels of glutamate and vesicular glutamate transporter 1 (VGLUT1) expression were reduced in both areas. Cortical glutamate release responded to K+ stimulation, whereas no peak release was observed in the HIPP of mutant mice. Synaptosomal-associated protein 25 (SNAP-25), glutamate/aspartate transporter (GLAST), glutamate transporter 1 (GLT1) and excitatory amino acid carrier 1 (EAAC1) were reduced in HIPP homogenates, where the adenosine triphosphate (ATP) content was lower. In contrast, glutamate transporter 1 and glial fibrillary acidic protein (GFAP) were found to be higher in the frontal cortex. The respiration rates of complex-I, II, IV, and the membrane potential were reduced in cortical mitochondria, where unaltered proton leak, F0F1-ATPase activity and ATP content, with increased hydrogen peroxide production (H2O2), were also observed. In contrast, complex-I respiration rate was significantly increased in hippocampal mitochondria, together with increased proton leak and H2O2 production. Moreover, loss of complex-IV and F0F1-ATPase activities were observed. These data suggest that impairments of mitochondrial bioenergetics might sustain the failure in the energy-requiring glutamatergic transmission. (C) 2012 Elsevier Inc. All rights reserved.
Glutamatergic alterations and mitochondrial impairment in a murine model of Alzheimer disease / Tommaso, Cassano; Gaetano, Serviddio; Gaetani, Silvana; Romano, Adele; Dipasquale, Pasqua; Cianci, Silvia; Francesco, Bellanti; Leonardo, Laconca; Antonino Davide, Romano; Iolanda, Padalino; Frank M., Laferla; Nicoletti, Ferdinando; Cuomo, Vincenzo; V., Vendemiale; Gianluigi, Vendemiale. - In: NEUROBIOLOGY OF AGING. - ISSN 0197-4580. - ELETTRONICO. - 33:6(2012), pp. 1121e1-1121e12. [10.1016/j.neurobiolaging.2011.09.021]
Glutamatergic alterations and mitochondrial impairment in a murine model of Alzheimer disease
GAETANI, SILVANA;ROMANO, ADELE;DIPASQUALE, PASQUA;CIANCI, SILVIA;NICOLETTI, Ferdinando;CUOMO, VINCENZO;
2012
Abstract
Deficits in glutamate neurotransmission and mitochondrial functions were detected in the frontal cortex (FC) and hippopcampus (HIPP) of aged 3 X Tg-Alzheimer's disease (AD) mice, compared with their wild type littermates (non-Tg). In particular, basal levels of glutamate and vesicular glutamate transporter 1 (VGLUT1) expression were reduced in both areas. Cortical glutamate release responded to K+ stimulation, whereas no peak release was observed in the HIPP of mutant mice. Synaptosomal-associated protein 25 (SNAP-25), glutamate/aspartate transporter (GLAST), glutamate transporter 1 (GLT1) and excitatory amino acid carrier 1 (EAAC1) were reduced in HIPP homogenates, where the adenosine triphosphate (ATP) content was lower. In contrast, glutamate transporter 1 and glial fibrillary acidic protein (GFAP) were found to be higher in the frontal cortex. The respiration rates of complex-I, II, IV, and the membrane potential were reduced in cortical mitochondria, where unaltered proton leak, F0F1-ATPase activity and ATP content, with increased hydrogen peroxide production (H2O2), were also observed. In contrast, complex-I respiration rate was significantly increased in hippocampal mitochondria, together with increased proton leak and H2O2 production. Moreover, loss of complex-IV and F0F1-ATPase activities were observed. These data suggest that impairments of mitochondrial bioenergetics might sustain the failure in the energy-requiring glutamatergic transmission. (C) 2012 Elsevier Inc. All rights reserved.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.