| First Author | Cassano T | Year | 2012 |
| Journal | Neurobiol Aging | Volume | 33 |
| Issue | 6 | Pages | 1121.e1-12 |
| PubMed ID | 22035587 | Mgi Jnum | J:188184 |
| Mgi Id | MGI:5439671 | Doi | 10.1016/j.neurobiolaging.2011.09.021 |
| Citation | Cassano T, et al. (2012) Glutamatergic alterations and mitochondrial impairment in a murine model of Alzheimer disease. Neurobiol Aging 33(6):1121.e1-12 |
| abstractText | Deficits in glutamate neurotransmission and mitochondrial functions were detected in the frontal cortex (FC) and hippopcampus (HIPP) of aged 3xTg-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. |
