| First Author | Calkins MJ | Year | 2011 |
| Journal | Biochim Biophys Acta | Volume | 1812 |
| Issue | 9 | Pages | 1182-9 |
| PubMed ID | 21549836 | Mgi Jnum | J:177294 |
| Mgi Id | MGI:5294708 | Doi | 10.1016/j.bbadis.2011.04.006 |
| Citation | Calkins MJ, et al. (2011) Assessment of newly synthesized mitochondrial DNA using BrdU labeling in primary neurons from Alzheimer's disease mice: Implications for impaired mitochondrial biogenesis and synaptic damage. Biochim Biophys Acta 1812(9):1182-9 |
| abstractText | The purpose of our study was to assess mitochondrial biogenesis and distribution in murine primary neurons. Using 5-bromo-2-deoxyuridine (BrdU) incorporation and primary neurons, we studied the mitochondrial biogenesis and mitochondrial distribution in hippocampal neurons from amyloid beta precursor protein (AbetaPP) transgenic mice and wild-type (WT) neurons treated with oxidative stressors, rotenone and H(2)O(2). We found that after 20h of labeling, BrdU incorporation was specific to porin-positive mitochondria. The proportion of mitochondrial area labeled with BrdU was 40.3+/-6.3% at 20h. The number of mitochondria with newly synthesized DNA was higher in AbetaPP neuronal cell bodies than in the cell bodies of WT neurons (AbetaPP, 45.23+/-2.67 BrdU-positive/cell body; WT, 32.92+/-2.49 BrdU-positive/cell body; p=0.005). In neurites, the number of BrdU-positive mitochondria decreased in AbetaPP cultures compared to WT neurons (AbetaPP, 0.105+/-0.008 BrdU-positive/mum neurite; WT, 0.220+/-0.036 BrdU-positive/mum neurite; p=0.010). Further, BrdU in the cell body increased when neurons were treated with low doses of H(2)O(2) (49.6+/-2.7 BrdU-positive/cell body, p=0.0002 compared to untreated cells), while the neurites showed decreased BrdU staining (0.122+/-0.010 BrdU-positive/mum neurite, p=0.005 compared to the untreated). BrdU labeling was increased in the cell body under rotenone treatment. Additionally, under rotenone treatment, the content of BrdU labeling decreased in neurites. These findings suggest that Abeta and mitochondrial toxins enhance mitochondrial fragmentation in the cell body, and may cause impaired axonal transport of mitochondria leading to synaptic degeneration. |
