| First Author | Tadić V | Year | 2019 |
| Journal | Neurobiol Aging | Volume | 75 |
| Pages | 209-222 | PubMed ID | 30597405 |
| Mgi Jnum | J:276157 | Mgi Id | MGI:6313918 |
| Doi | 10.1016/j.neurobiolaging.2018.11.019 | Citation | Tadic V, et al. (2019) Investigation of mitochondrial calcium uniporter role in embryonic and adult motor neurons from G93A(hSOD1) mice. Neurobiol Aging 75:209-222 |
| abstractText | Amyotrophic lateral sclerosis is characterized by progressive death of motor neurons (MNs) with glutamate excitotoxicity and mitochondrial Ca(2+) overload as critical mechanisms in disease pathophysiology. We used MNs from G93A(hSOD1) and nontransgenic embryonic cultures and adult mice to analyze the expression of the main mitochondrial calcium uniporter (MCU). MCU was overexpressed in cultured embryonic G93A(hSOD1) MNs compared to nontransgenic MNs but downregulated in MNs from adult G93A(hSOD1) mice. Furthermore, cultured embryonic G93A(hSOD1) were rescued from kainate-induced excitotoxicity by the Ca(2+)/calmodulin-dependent protein kinase type II inhibitor; KN-62, which reduced MCU expression in G93A(hSOD1) MNs. MCU activation via kaempferol neither altered MCU expression nor influenced MN survival. However, its acute application served as a fine tool to study spontaneous Ca(2+) activity in cultured neurons which was significantly altered by the mutated hSOD1. Pharmacological manipulation of MCU expression might open new possibilities to fight excitotoxic damage in amyotrophic lateral sclerosis. |
