| First Author | Orem BC | Year | 2020 |
| Journal | Neurobiol Dis | Volume | 146 |
| Pages | 105123 | PubMed ID | 33011333 |
| Mgi Jnum | J:305148 | Mgi Id | MGI:6503616 |
| Doi | 10.1016/j.nbd.2020.105123 | Citation | Orem BC, et al. (2020) IP3R-mediated intra-axonal Ca(2+) release contributes to secondary axonal degeneration following contusive spinal cord injury. Neurobiol Dis 146:105123 |
| abstractText | Secondary axonal loss contributes to the persistent functional disability following trauma. Consequently, preserving axons following spinal cord injury (SCI) is a major therapeutic goal to improve neurological outcome; however, the complex molecular mechanisms that mediate secondary axonal degeneration remain unclear. We previously showed that IP3R-mediated Ca(2+) release contributes to axonal dieback and axonal loss following an ex vivo laser-induced SCI. Nevertheless, targeting IP3R in a clinically relevant in vivo model of SCI and determining its contribution to secondary axonal degeneration has yet to be explored. Here we used intravital two-photon excitation microscopy to assess the role of IP3R in secondary axonal degeneration in real-time after a contusive-SCI in vivo. To visualize Ca(2+) changes specifically in spinal axons over time, adult 6-8 week-old triple transgenic Avil-Cre:Ai9:Ai95 (sensory neuron-specific expression of tdTomato and the genetic calcium indicator GCaMP6f) mice were subjected to a mild (30 kdyn) T12 contusive-SCI and received delayed treatment with the IP3R blocker 2-APB (100 muM, intrathecal delivery at 3, and 24 h following injury) or vehicle control. To determine the IP3R subtype involved, we knocked-down IP3R3 using capped phosphodiester oligonucleotides. Delayed treatment with 2-APB significantly reduced axonal spheroids, increased axonal survival, and reduced intra-axonal Ca(2+) accumulation within dorsal column axons at 24 h following SCI in vivo. Additionally, knockdown of IP3R3 yielded increased axon survival 24 h post-SCI. These results suggest that IP3R-mediated Ca(2+) release contributes to secondary axonal degeneration in vivo following SCI. |
