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

Neurobiology of aging | 2017

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.

Pubmed ID: 28753475 RIS Download

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Anti-NeuN, clone A60, Alexa Fluor 488 conjugated (antibody)

RRID:AB_2149209

This monoclonal targets NeuN clone A60 Alexa Fluor 488 conjugated

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smoothelin (H-300) (antibody)

RRID:AB_2193677

This polyclonal targets SMTN

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MRCL3/MRLC2/MYL9 (FL-172) (antibody)

RRID:AB_2148039

This polyclonal targets MYL9, LOC391722, MRCL3, MRLC2

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Anti-GAPDH (antibody)

RRID:AB_10615768

This polyclonal targets GAPDH

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Anti-NeuN (antibody)

RRID:AB_2298772

This monoclonal targets NeuN

View all literature mentions

IRDye 800CW Goat anti-Rabbit IgG (antibody)

RRID:AB_621843

This polyclonal secondary targets IgG

View all literature mentions

Presenilin 1 (D39D1) Rabbit mAb (antibody)

RRID:AB_10706356

This monoclonal targets Presenilin 1 (D39D1) Rabbit mAb

View all literature mentions

Anti-NeuN, clone A60, Alexa Fluor 488 conjugated (antibody)

RRID:AB_2149209

This monoclonal targets NeuN clone A60 Alexa Fluor 488 conjugated

View all literature mentions

smoothelin (H-300) (antibody)

RRID:AB_2193677

This polyclonal targets SMTN

View all literature mentions

MRCL3/MRLC2/MYL9 (FL-172) (antibody)

RRID:AB_2148039

This polyclonal targets MYL9, LOC391722, MRCL3, MRLC2

View all literature mentions

Anti-GAPDH (antibody)

RRID:AB_10615768

This polyclonal targets GAPDH

View all literature mentions

Anti-NeuN (antibody)

RRID:AB_2298772

This monoclonal targets NeuN

View all literature mentions

IRDye 800CW Goat anti-Rabbit IgG (antibody)

RRID:AB_621843

This polyclonal secondary targets IgG

View all literature mentions

Presenilin 1 (D39D1) Rabbit mAb (antibody)

RRID:AB_10706356

This monoclonal targets Presenilin 1 (D39D1) Rabbit mAb

View all literature mentions