High levels of 27-hydroxycholesterol results in synaptic plasticity alterations in the hippocampus

Abstract Alterations in brain cholesterol homeostasis in midlife are correlated with a higher risk of developing Alzheimer’s disease (AD). However, global cholesterol-lowering therapies have yielded mixed results when it comes to slowing down or preventing cognitive decline in AD. We used the transg...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Raul Loera-Valencia, Erika Vazquez-Juarez, Alberto Muñoz, Gorka Gerenu, Marta Gómez-Galán, Maria Lindskog, Javier DeFelipe, Angel Cedazo-Minguez, Paula Merino-Serrais
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0b049b45ec844c18afc7850c0fa00835
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:0b049b45ec844c18afc7850c0fa00835
record_format	dspace
spelling	oai:doaj.org-article:0b049b45ec844c18afc7850c0fa008352021-12-02T14:11:31ZHigh levels of 27-hydroxycholesterol results in synaptic plasticity alterations in the hippocampus10.1038/s41598-021-83008-32045-2322https://doaj.org/article/0b049b45ec844c18afc7850c0fa008352021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-83008-3https://doaj.org/toc/2045-2322Abstract Alterations in brain cholesterol homeostasis in midlife are correlated with a higher risk of developing Alzheimer’s disease (AD). However, global cholesterol-lowering therapies have yielded mixed results when it comes to slowing down or preventing cognitive decline in AD. We used the transgenic mouse model Cyp27Tg, with systemically high levels of 27-hydroxycholesterol (27-OH) to examine long-term potentiation (LTP) in the hippocampal CA1 region, combined with dendritic spine reconstruction of CA1 pyramidal neurons to detect morphological and functional synaptic alterations induced by 27-OH high levels. Our results show that elevated 27-OH levels lead to enhanced LTP in the Schaffer collateral-CA1 synapses. This increase is correlated with abnormally large dendritic spines in the stratum radiatum. Using immunohistochemistry for synaptopodin (actin-binding protein involved in the recruitment of the spine apparatus), we found a significantly higher density of synaptopodin-positive puncta in CA1 in Cyp27Tg mice. We hypothesize that high 27-OH levels alter synaptic potentiation and could lead to dysfunction of fine-tuned processing of information in hippocampal circuits resulting in cognitive impairment. We suggest that these alterations could be detrimental for synaptic function and cognition later in life, representing a potential mechanism by which hypercholesterolemia could lead to alterations in memory function in neurodegenerative diseases.Raul Loera-ValenciaErika Vazquez-JuarezAlberto MuñozGorka GerenuMarta Gómez-GalánMaria LindskogJavier DeFelipeAngel Cedazo-MinguezPaula Merino-SerraisNature 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 Raul Loera-Valencia Erika Vazquez-Juarez Alberto Muñoz Gorka Gerenu Marta Gómez-Galán Maria Lindskog Javier DeFelipe Angel Cedazo-Minguez Paula Merino-Serrais High levels of 27-hydroxycholesterol results in synaptic plasticity alterations in the hippocampus
description	Abstract Alterations in brain cholesterol homeostasis in midlife are correlated with a higher risk of developing Alzheimer’s disease (AD). However, global cholesterol-lowering therapies have yielded mixed results when it comes to slowing down or preventing cognitive decline in AD. We used the transgenic mouse model Cyp27Tg, with systemically high levels of 27-hydroxycholesterol (27-OH) to examine long-term potentiation (LTP) in the hippocampal CA1 region, combined with dendritic spine reconstruction of CA1 pyramidal neurons to detect morphological and functional synaptic alterations induced by 27-OH high levels. Our results show that elevated 27-OH levels lead to enhanced LTP in the Schaffer collateral-CA1 synapses. This increase is correlated with abnormally large dendritic spines in the stratum radiatum. Using immunohistochemistry for synaptopodin (actin-binding protein involved in the recruitment of the spine apparatus), we found a significantly higher density of synaptopodin-positive puncta in CA1 in Cyp27Tg mice. We hypothesize that high 27-OH levels alter synaptic potentiation and could lead to dysfunction of fine-tuned processing of information in hippocampal circuits resulting in cognitive impairment. We suggest that these alterations could be detrimental for synaptic function and cognition later in life, representing a potential mechanism by which hypercholesterolemia could lead to alterations in memory function in neurodegenerative diseases.
format	article
author	Raul Loera-Valencia Erika Vazquez-Juarez Alberto Muñoz Gorka Gerenu Marta Gómez-Galán Maria Lindskog Javier DeFelipe Angel Cedazo-Minguez Paula Merino-Serrais
author_facet	Raul Loera-Valencia Erika Vazquez-Juarez Alberto Muñoz Gorka Gerenu Marta Gómez-Galán Maria Lindskog Javier DeFelipe Angel Cedazo-Minguez Paula Merino-Serrais
author_sort	Raul Loera-Valencia
title	High levels of 27-hydroxycholesterol results in synaptic plasticity alterations in the hippocampus
title_short	High levels of 27-hydroxycholesterol results in synaptic plasticity alterations in the hippocampus
title_full	High levels of 27-hydroxycholesterol results in synaptic plasticity alterations in the hippocampus
title_fullStr	High levels of 27-hydroxycholesterol results in synaptic plasticity alterations in the hippocampus
title_full_unstemmed	High levels of 27-hydroxycholesterol results in synaptic plasticity alterations in the hippocampus
title_sort	high levels of 27-hydroxycholesterol results in synaptic plasticity alterations in the hippocampus
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/0b049b45ec844c18afc7850c0fa00835
work_keys_str_mv	AT raulloeravalencia highlevelsof27hydroxycholesterolresultsinsynapticplasticityalterationsinthehippocampus AT erikavazquezjuarez highlevelsof27hydroxycholesterolresultsinsynapticplasticityalterationsinthehippocampus AT albertomunoz highlevelsof27hydroxycholesterolresultsinsynapticplasticityalterationsinthehippocampus AT gorkagerenu highlevelsof27hydroxycholesterolresultsinsynapticplasticityalterationsinthehippocampus AT martagomezgalan highlevelsof27hydroxycholesterolresultsinsynapticplasticityalterationsinthehippocampus AT marialindskog highlevelsof27hydroxycholesterolresultsinsynapticplasticityalterationsinthehippocampus AT javierdefelipe highlevelsof27hydroxycholesterolresultsinsynapticplasticityalterationsinthehippocampus AT angelcedazominguez highlevelsof27hydroxycholesterolresultsinsynapticplasticityalterationsinthehippocampus AT paulamerinoserrais highlevelsof27hydroxycholesterolresultsinsynapticplasticityalterationsinthehippocampus
_version_	1718391827034275840

High levels of 27-hydroxycholesterol results in synaptic plasticity alterations in the hippocampus

Ejemplares similares