| First Author | Liu X | Year | 2012 |
| Journal | Cell | Volume | 150 |
| Issue | 5 | Pages | 1055-67 |
| PubMed ID | 22939628 | Mgi Jnum | J:187976 |
| Mgi Id | MGI:5438859 | Doi | 10.1016/j.cell.2012.06.052 |
| Citation | Liu X, et al. (2012) Role of leaky neuronal ryanodine receptors in stress- induced cognitive dysfunction. Cell 150(5):1055-67 |
| abstractText | The type 2 ryanodine receptor/calcium release channel (RyR2), required for excitation-contraction coupling in the heart, is abundant in the brain. Chronic stress induces catecholamine biosynthesis and release, stimulating beta-adrenergic receptors and activating cAMP signaling pathways in neurons. In a murine chronic restraint stress model, neuronal RyR2 were phosphorylated by protein kinase A (PKA), oxidized, and nitrosylated, resulting in depletion of the stabilizing subunit calstabin2 (FKBP12.6) from the channel complex and intracellular calcium leak. Stress-induced cognitive dysfunction, including deficits in learning and memory, and reduced long-term potentiation (LTP) at the hippocampal CA3-CA1 connection were rescued by oral administration of S107, a compound developed in our laboratory that stabilizes RyR2-calstabin2 interaction, or by genetic ablation of the RyR2 PKA phosphorylation site at serine 2808. Thus, neuronal RyR2 remodeling contributes to stress-induced cognitive dysfunction. Leaky RyR2 could be a therapeutic target for treatment of stress-induced cognitive dysfunction. |
