Glutamatergic alterations and mitochondrial impairment in a murine model of Alzheimer disease
| Autor: | Adele Romano, Gianluigi Vendemiale, Francesco Bellanti, Antonino Davide Romano, Tommaso Cassano, Gaetano Serviddio, Silvia Cianci, Frank M. LaFerla, Vincenzo Cuomo, Leonardo Laconca, Silvana Gaetani, Pasqua Dipasquale, Iolanda Padalino, Ferdinando Nicoletti |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Male
Aging medicine.medical_specialty Synaptosomal-Associated Protein 25 hippocampus microdialysis Vesicular glutamate transporter 1 3 x tg-ad mice Glutamic Acid Mice Transgenic glutamate 3tg-ad mice 3×tg-ad mice Mitochondrion frontal cortex mitochondria alzheimer’s disease alzheimer's disease Glutamatergic chemistry.chemical_compound Mice Alzheimer Disease Internal medicine medicine Glutamate aspartate transporter Animals biology Glial fibrillary acidic protein General Neuroscience Glutamate receptor Glutamic acid Excitatory Amino Acid Transporter 1 Disease Models Animal Endocrinology Biochemistry chemistry Excitatory Amino Acid Transporter 2 Vesicular Glutamate Transport Protein 1 biology.protein Neurology (clinical) Geriatrics and Gerontology Adenosine triphosphate Developmental Biology |
| Popis: | Deficits in glutamate neurotransmission and mitochondrial functions were detected in the frontal cortex (FC) and hippopcampus (HIPP) of aged 3×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, F(0)F(1)-ATPase activity and ATP content, with increased hydrogen peroxide production (H(2)O(2)), were also observed. In contrast, complex-I respiration rate was significantly increased in hippocampal mitochondria, together with increased proton leak and H(2)O(2) production. Moreover, loss of complex-IV and F(0)F(1)-ATPase activities were observed. These data suggest that impairments of mitochondrial bioenergetics might sustain the failure in the energy-requiring glutamatergic transmission. |
| Databáze: | OpenAIRE |
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