IGF-1 deficiency impairs neurovascular coupling in mice implications for cerebromicrovascular aging /

Aging is associated with marked deficiency in circulating IGF-1, which has been shown to contribute to age-related cognitive decline. Impairment of moment-to-moment adjustment of cerebral blood flow (CBF) via neurovascular coupling is thought to play a critical role in the genesis of age-related cog...

Teljes leírás

Elmentve itt :
Bibliográfiai részletek
Szerzők: Tóth Péter József
Tarantini Stefano
Ashpole Nicole M.
Tucsek Zsuzsanna
Milne Ginger L.
Valcarcel-Ares Noa M.
Menyhárt Ákos
Farkas Eszter
Sonntag William E.
Csiszár Anna
Ungvári Zoltán István
Dokumentumtípus: Cikk
Megjelent: Wiley-Blackwell Publishing Ltd. 2015
Sorozat:AGING CELL 14 No. 6
doi:10.1111/acel.12372

mtmt:2920558
Online Access:http://publicatio.bibl.u-szeged.hu/7947
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520 3 |a Aging is associated with marked deficiency in circulating IGF-1, which has been shown to contribute to age-related cognitive decline. Impairment of moment-to-moment adjustment of cerebral blood flow (CBF) via neurovascular coupling is thought to play a critical role in the genesis of age-related cognitive impairment. To establish the link between IGF-1 deficiency and cerebromicrovascular impairment, neurovascular coupling mechanisms were studied in a novel mouse model of IGF-1 deficiency (Igf1f/f -TBG-Cre-AAV8) and accelerated vascular aging. We found that IGF-1-deficient mice exhibit neurovascular uncoupling and show a deficit in hippocampal-dependent spatial memory test, mimicking the aging phenotype. IGF-1 deficiency significantly impaired cerebromicrovascular endothelial function decreasing NO mediation of neurovascular coupling. IGF-1 deficiency also impaired glutamate-mediated CBF responses, likely due to dysregulation of astrocytic expression of metabotropic glutamate receptors and impairing mediation of CBF responses by eicosanoid gliotransmitters. Collectively, we demonstrate that IGF-1 deficiency promotes cerebromicrovascular dysfunction and neurovascular uncoupling mimicking the aging phenotype, which are likely to contribute to cognitive impairment. 
700 0 1 |a Tarantini Stefano  |e aut 
700 0 1 |a Ashpole Nicole M.  |e aut 
700 0 1 |a Tucsek Zsuzsanna  |e aut 
700 0 1 |a Milne Ginger L.  |e aut 
700 0 2 |a Valcarcel-Ares Noa M.  |e aut 
700 0 2 |a Menyhárt Ákos  |e aut 
700 0 2 |a Farkas Eszter  |e aut 
700 0 2 |a Sonntag William E.  |e aut 
700 0 2 |a Csiszár Anna  |e aut 
700 0 2 |a Ungvári Zoltán István  |e aut 
856 4 0 |u http://publicatio.bibl.u-szeged.hu/7947/1/Toth_et_al_2015_Aging_Cell_u.pdf  |z Dokumentum-elérés