| First Author | Lee W | Year | 2013 |
| Journal | Neurobiol Dis | Volume | 58 |
| Pages | 192-9 | PubMed ID | 23756199 |
| Mgi Jnum | J:201703 | Mgi Id | MGI:5515290 |
| Doi | 10.1016/j.nbd.2013.06.002 | Citation | Lee W, et al. (2013) Enhanced Ca(2+)-dependent glutamate release from astrocytes of the BACHD Huntington's disease mouse model. Neurobiol Dis 58:192-9 |
| abstractText | Huntington's disease (HD) causes preferential loss of a subset of neurons in the brain although the huntingtin protein is expressed broadly in various neural cell types, including astrocytes. Glutamate-mediated excitotoxicity is thought to cause selective neuronal injury, and brain astrocytes have a central role in regulating extracellular glutamate. To determine whether full-length mutant huntingtin expression causes a cell-autonomous phenotype and perturbs astrocyte gliotransmitter release, we studied cultured cortical astrocytes from BACHD mice. Here, we report augmented glutamate release through Ca(2+)-dependent exocytosis from BACHD astrocytes. Although such release is usually dependent on cytosolic Ca(2+) levels, surprisingly, we found that BACHD astrocytes displayed Ca(2+) dynamics comparable to those in wild type astrocytes. These results point to a possible involvement of other factors in regulating Ca(2+)-dependent/vesicular release of glutamate from astrocytes. We found a biochemical footprint that would lead to increased availability of cytosolic glutamate in BACHD astrocytes: i) augmented de novo glutamate synthesis due to an increase in the level of the astrocyte specific mitochondrial enzyme pyruvate carboxylase; and ii) unaltered conversion of glutamate to glutamine, as there were no changes in the expression level of the astrocyte specific enzyme glutamine synthetase. This work identifies a new mechanism in astrocytes that could lead to increased levels of extracellular glutamate in HD and thus may contribute to excitotoxicity in this devastating disease. |
