| First Author | He XP | Year | 2010 |
| Journal | J Neurosci | Volume | 30 |
| Issue | 18 | Pages | 6188-96 |
| PubMed ID | 20445044 | Mgi Jnum | J:160562 |
| Mgi Id | MGI:4454617 | Doi | 10.1523/JNEUROSCI.5821-09.2010 |
| Citation | He XP, et al. (2010) Disruption of TrkB-mediated phospholipase Cgamma signaling inhibits limbic epileptogenesis. J Neurosci 30(18):6188-96 |
| abstractText | The BDNF receptor, TrkB, is critical to limbic epileptogenesis, but the responsible downstream signaling pathways are unknown. We hypothesized that TrkB-dependent activation of phospholipase Cgamma1 (PLCgamma1) signaling is the key pathway and tested this in trkB(PLC/PLC) mice carrying a mutation (Y816F) that uncouples TrkB from PLCgamma1. Biochemical measures revealed activation of both TrkB and PLCgamma1 in hippocampi in the pilocarpine and kindling models in wild-type mice. PLCgamma1 activation was decreased in hippocampi isolated from trkB(PLC/PLC) compared with control mice. Epileptogenesis assessed by development of kindling was inhibited in trkB(PLC/PLC) compared with control mice. Long-term potentiation of the mossy fiber-CA3 pyramid synapse was impaired in slices of trkB(PLC/PLC) mice. We conclude that TrkB-dependent activation of PLCgamma1 signaling is an important molecular mechanism of limbic epileptogenesis. Elucidating signaling pathways activated by a cell membrane receptor in animal models of CNS disorders promises to reveal novel targets for specific and effective therapeutic intervention. |
