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...
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Dokumentumtípus: | Cikk |
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Wiley-Blackwell Publishing Ltd.
2015
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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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040 | |a SZTE Publicatio Repozitórium |b hun | ||
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100 | 1 | |a Tóth Péter József | |
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260 | |a Wiley-Blackwell Publishing Ltd. |c 2015 | ||
300 | |a 1034-1044 | ||
490 | 0 | |a AGING CELL |v 14 No. 6 | |
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 |