| First Author | Toussay X | Year | 2017 |
| Journal | Neurobiol Aging | Volume | 58 |
| Pages | 201-212 | PubMed ID | 28753475 |
| Mgi Jnum | J:249747 | Mgi Id | MGI:6092621 |
| Doi | 10.1016/j.neurobiolaging.2017.06.015 | Citation | Toussay X, et al. (2017) Presenilin 1 mutation decreases both calcium and contractile responses in cerebral arteries. Neurobiol Aging 58:201-212 |
| abstractText | Mutations or upregulation in presenilin 1 (PS1) gene are found in familial early-onset Alzheimer's disease or sporadic late-onset Alzheimer's disease, respectively. PS1 has been essentially studied in neurons and its mutation was shown to alter intracellular calcium (Ca(2+)) signals. Here, we showed that PS1 is expressed in smooth muscle cells (SMCs) of mouse cerebral arteries, and we assessed the effects of the deletion of exon 9 of PS1 (PS1dE9) on Ca(2+) signals and contractile responses of vascular SMC. Agonist-induced contraction of cerebral vessels was significantly decreased in PS1dE9 both in vivo and ex vivo. Spontaneous activity of Ca(2+) sparks through ryanodine-sensitive channels (RyR) was unchanged, whereas the RyR-mediated Ca(2+)-release activated by caffeine was shorter in PS1dE9 SMC when compared with control. Moreover, PS1dE9 mutation decreased the caffeine-activated capacitive Ca(2+) entry, and inhibitors of SERCA pumps reversed the effects of PS1dE9 on Ca(2+) signals. PS1dE9 mutation also leads to the increased expression of SERCA3, phospholamban, and RyR3. These results show that PS1 plays a crucial role in the cerebrovascular system and the vascular reactivity is decreased through altered Ca(2+) signals in PS1dE9 mutant mice. |
