Endothelin-1 mediated vasoconstriction leads to memory impairment and synaptic dysfunction

Abstract Cerebrovascular lesions seen as white matter hyperintensity in MRI of elderly population caused due to micro-infracts and micro-bleeds contributes to vascular dementia. Such vascular insult caused by impairment in blood flow to specific area in brain involving small vessels can gradually wo...

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Autores principales:	Latha Diwakar, Ruturaj Gowaikar, Keerthana Chithanathan, Barathan Gnanabharathi, Deepika Singh Tomar, Vijayalakshmi Ravindranath
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/74d9ee203fc4469cbc7f42df2d7852c3
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spelling	oai:doaj.org-article:74d9ee203fc4469cbc7f42df2d7852c32021-12-02T11:37:19ZEndothelin-1 mediated vasoconstriction leads to memory impairment and synaptic dysfunction10.1038/s41598-021-84258-x2045-2322https://doaj.org/article/74d9ee203fc4469cbc7f42df2d7852c32021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84258-xhttps://doaj.org/toc/2045-2322Abstract Cerebrovascular lesions seen as white matter hyperintensity in MRI of elderly population caused due to micro-infracts and micro-bleeds contributes to vascular dementia. Such vascular insult caused by impairment in blood flow to specific area in brain involving small vessels can gradually worsen the pathology leading to cognitive deficits. In the present study we developed a transient model of vaso-constriction to study the impact of such pathology by bilateral injection of ET-1 (Endothelin-1; a 21 amino acid vasoconstricting peptide) into lateral ventricles of C57 mice. The impediment in cerebral blood flow decreased CD31 expression in endothelial cells lining the blood vessels around the hippocampal region, leading to memory deficits after 7 days. Activity dependent protein translation, critical for synaptic plasticity was absent in synaptoneurosomes prepared from hippocampal tissue. Further, Akt1- mTOR signaling cascade was downregulated indicating the possible cause for loss of activity dependent protein translation. However, these effects were reversed after 30 days indicating the ephemeral nature of deficits following a single vascular insult. Present study demonstrates that vasoconstriction leading to memory deficit and decline in activity dependent protein translation in hippocampus as a potential molecular mechanism impacting synaptic plasticity.Latha DiwakarRuturaj GowaikarKeerthana ChithanathanBarathan GnanabharathiDeepika Singh TomarVijayalakshmi RavindranathNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Latha Diwakar Ruturaj Gowaikar Keerthana Chithanathan Barathan Gnanabharathi Deepika Singh Tomar Vijayalakshmi Ravindranath Endothelin-1 mediated vasoconstriction leads to memory impairment and synaptic dysfunction
description	Abstract Cerebrovascular lesions seen as white matter hyperintensity in MRI of elderly population caused due to micro-infracts and micro-bleeds contributes to vascular dementia. Such vascular insult caused by impairment in blood flow to specific area in brain involving small vessels can gradually worsen the pathology leading to cognitive deficits. In the present study we developed a transient model of vaso-constriction to study the impact of such pathology by bilateral injection of ET-1 (Endothelin-1; a 21 amino acid vasoconstricting peptide) into lateral ventricles of C57 mice. The impediment in cerebral blood flow decreased CD31 expression in endothelial cells lining the blood vessels around the hippocampal region, leading to memory deficits after 7 days. Activity dependent protein translation, critical for synaptic plasticity was absent in synaptoneurosomes prepared from hippocampal tissue. Further, Akt1- mTOR signaling cascade was downregulated indicating the possible cause for loss of activity dependent protein translation. However, these effects were reversed after 30 days indicating the ephemeral nature of deficits following a single vascular insult. Present study demonstrates that vasoconstriction leading to memory deficit and decline in activity dependent protein translation in hippocampus as a potential molecular mechanism impacting synaptic plasticity.
format	article
author	Latha Diwakar Ruturaj Gowaikar Keerthana Chithanathan Barathan Gnanabharathi Deepika Singh Tomar Vijayalakshmi Ravindranath
author_facet	Latha Diwakar Ruturaj Gowaikar Keerthana Chithanathan Barathan Gnanabharathi Deepika Singh Tomar Vijayalakshmi Ravindranath
author_sort	Latha Diwakar
title	Endothelin-1 mediated vasoconstriction leads to memory impairment and synaptic dysfunction
title_short	Endothelin-1 mediated vasoconstriction leads to memory impairment and synaptic dysfunction
title_full	Endothelin-1 mediated vasoconstriction leads to memory impairment and synaptic dysfunction
title_fullStr	Endothelin-1 mediated vasoconstriction leads to memory impairment and synaptic dysfunction
title_full_unstemmed	Endothelin-1 mediated vasoconstriction leads to memory impairment and synaptic dysfunction
title_sort	endothelin-1 mediated vasoconstriction leads to memory impairment and synaptic dysfunction
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/74d9ee203fc4469cbc7f42df2d7852c3
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Endothelin-1 mediated vasoconstriction leads to memory impairment and synaptic dysfunction

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