Presenilin 1 mutation decreases both calcium and contractile responses in cerebral arteries
Neurobiology of Aging. 2017-10-01; 58: 201-212
DOI: 10.1016/j.neurobiolaging.2017.06.015
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1. Neurobiol Aging. 2017 Oct;58:201-212. doi: 10.1016/j.neurobiolaging.2017.06.015.
Epub 2017 Jun 24.
Presenilin 1 mutation decreases both calcium and contractile responses in
cerebral arteries.
Toussay X(1), Morel JL(2), Biendon N(2), Rotureau L(1), Legeron FP(2), Boutonnet
MC(2), Cho YH(3), Macrez N(4).
Author information:
(1)University Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293,
Bordeaux, France; CNRS, Centre de Neurosciences Intégratives et Cognitives, UMR
5228, Bordeaux, France.
(2)University Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293,
Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293,
Bordeaux, France.
(3)CNRS, Institut de Neurosciences Cognitives et Intégratives d’Aquitaine, UMR
5287, Bordeaux, France.
(4)University Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293,
Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293,
Bordeaux, France. Electronic address: .
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.
Copyright © 2017 Elsevier Inc. All rights reserved.
DOI: 10.1016/j.neurobiolaging.2017.06.015
PMID: 28753475 [Indexed for MEDLINE]