Presenilin 1 mutation decreases both calcium and contractile responses in cerebral arteries

NEUROBIOLOGY OF AGING

卷:58

Article

Toussay, Xavier^1,2,5  Morel, Jean-Luc^1,3  Biendon, Nathalie^1,3  Rotureau, Lolita^1,2  Legeron, Francois-Pierre^1,3  Boutonnet, Marie-Charlotte^1,3  Cho, Yoon H.⁴  Macrez, Nathalie^1,3 

[1] Univ Bordeaux, Inst Malad Neurodegenerat, UMR 5293, Bordeaux, France

[2] CNRS, Ctr Neurosci Integrat & Cognit, UMR 5228, Bordeaux, France

[3] CNRS, Inst Malad Neurodegenerat, UMR 5293, Bordeaux, France

[4] CNRS, Inst Neurosci Cognit & Integrat Aquitaine, UMR 5287, Bordeaux, France

[5] Univ Ottawa, Ottawa Hosp Res Inst, Fac Med, Dept Cellular & Mol Med, Ottawa, ON, Canada

关键词: Presenilin;    Calcium;    Smooth muscle cells;    Contraction;    Cerebral arteries;    Alzheimer's disease;   

DOI  :  10.1016/j.neurobiolaging.2017.06.015

来源: Elsevier

【 摘 要 】

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 (Ca2+) 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 Ca2+ 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 Ca2+ sparks through ryanodine-sensitive channels (RyR) was unchanged, whereas the RyR-mediated Ca2+-release activated by caffeine was shorter in PS1dE9 SMC when compared with control. Moreover, PS1dE9 mutation decreased the caffeine-activated capacitive Ca2+ entry, and inhibitors of SERCA pumps reversed the effects of PS1dE9 on Ca2+ 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 Ca2+ signals in PS1dE9 mutant mice. (C) 2017 Elsevier Inc. All rights reserved.

【 授权许可】

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