α7 Nicotinic receptor-mediated astrocytic gliotransmitter release: Aβ effects in a preclinical Alzheimer's mouse model.

It is now recognized that astrocytes participate in synaptic communication through intimate interactions with neurons. A principal mechanism is through the release of gliotransmitters (GTs) such as ATP, D-serine and most notably, glutamate, in response to astrocytic calcium elevations. We and others...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Tiina Maria Pirttimaki, Neela Krushna Codadu, Alia Awni, Pandey Pratik, David Andrew Nagel, Eric James Hill, Kelly Tennyson Dineley, H Rheinallt Parri
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/12a024508b614209a9d942692f6b1074
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:12a024508b614209a9d942692f6b1074
record_format	dspace
spelling	oai:doaj.org-article:12a024508b614209a9d942692f6b10742021-11-18T08:44:15Zα7 Nicotinic receptor-mediated astrocytic gliotransmitter release: Aβ effects in a preclinical Alzheimer's mouse model.1932-620310.1371/journal.pone.0081828https://doaj.org/article/12a024508b614209a9d942692f6b10742013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24312364/?tool=EBIhttps://doaj.org/toc/1932-6203It is now recognized that astrocytes participate in synaptic communication through intimate interactions with neurons. A principal mechanism is through the release of gliotransmitters (GTs) such as ATP, D-serine and most notably, glutamate, in response to astrocytic calcium elevations. We and others have shown that amyloid-β (Aβ), the toxic trigger for Alzheimer's disease (AD), interacts with hippocampal α7 nicotinic acetylcholine receptors (nAChRs). Since α7nAChRs are highly permeable to calcium and are expressed on hippocampal astrocytes, we investigated whether Aβ could activate astrocytic α7nAChRs in hippocampal slices and induce GT glutamate release. We found that biologically-relevant concentrations of Aβ1-42 elicited α7nAChR-dependent calcium elevations in hippocampal CA1 astrocytes and induced NMDAR-mediated slow inward currents (SICs) in CA1 neurons. In the Tg2576 AD mouse model for Aβ over-production and accumulation, we found that spontaneous astrocytic calcium elevations were of higher frequency compared to wildtype (WT). The frequency and kinetic parameters of AD mice SICs indicated enhanced gliotransmission, possibly due to increased endogenous Aβ observed in this model. Activation of α7nAChRs on WT astrocytes increased spontaneous inward currents on pyramidal neurons while α7nAChRs on astrocytes of AD mice were abrogated. These findings suggest that, at an age that far precedes the emergence of cognitive deficits and plaque deposition, this mouse model for AD-like amyloidosis exhibits augmented astrocytic activity and glutamate GT release suggesting possible repercussions for preclinical AD hippocampal neural networks that contribute to subsequent cognitive decline.Tiina Maria PirttimakiNeela Krushna CodaduAlia AwniPandey PratikDavid Andrew NagelEric James HillKelly Tennyson DineleyH Rheinallt ParriPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 11, p e81828 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tiina Maria Pirttimaki Neela Krushna Codadu Alia Awni Pandey Pratik David Andrew Nagel Eric James Hill Kelly Tennyson Dineley H Rheinallt Parri α7 Nicotinic receptor-mediated astrocytic gliotransmitter release: Aβ effects in a preclinical Alzheimer's mouse model.
description	It is now recognized that astrocytes participate in synaptic communication through intimate interactions with neurons. A principal mechanism is through the release of gliotransmitters (GTs) such as ATP, D-serine and most notably, glutamate, in response to astrocytic calcium elevations. We and others have shown that amyloid-β (Aβ), the toxic trigger for Alzheimer's disease (AD), interacts with hippocampal α7 nicotinic acetylcholine receptors (nAChRs). Since α7nAChRs are highly permeable to calcium and are expressed on hippocampal astrocytes, we investigated whether Aβ could activate astrocytic α7nAChRs in hippocampal slices and induce GT glutamate release. We found that biologically-relevant concentrations of Aβ1-42 elicited α7nAChR-dependent calcium elevations in hippocampal CA1 astrocytes and induced NMDAR-mediated slow inward currents (SICs) in CA1 neurons. In the Tg2576 AD mouse model for Aβ over-production and accumulation, we found that spontaneous astrocytic calcium elevations were of higher frequency compared to wildtype (WT). The frequency and kinetic parameters of AD mice SICs indicated enhanced gliotransmission, possibly due to increased endogenous Aβ observed in this model. Activation of α7nAChRs on WT astrocytes increased spontaneous inward currents on pyramidal neurons while α7nAChRs on astrocytes of AD mice were abrogated. These findings suggest that, at an age that far precedes the emergence of cognitive deficits and plaque deposition, this mouse model for AD-like amyloidosis exhibits augmented astrocytic activity and glutamate GT release suggesting possible repercussions for preclinical AD hippocampal neural networks that contribute to subsequent cognitive decline.
format	article
author	Tiina Maria Pirttimaki Neela Krushna Codadu Alia Awni Pandey Pratik David Andrew Nagel Eric James Hill Kelly Tennyson Dineley H Rheinallt Parri
author_facet	Tiina Maria Pirttimaki Neela Krushna Codadu Alia Awni Pandey Pratik David Andrew Nagel Eric James Hill Kelly Tennyson Dineley H Rheinallt Parri
author_sort	Tiina Maria Pirttimaki
title	α7 Nicotinic receptor-mediated astrocytic gliotransmitter release: Aβ effects in a preclinical Alzheimer's mouse model.
title_short	α7 Nicotinic receptor-mediated astrocytic gliotransmitter release: Aβ effects in a preclinical Alzheimer's mouse model.
title_full	α7 Nicotinic receptor-mediated astrocytic gliotransmitter release: Aβ effects in a preclinical Alzheimer's mouse model.
title_fullStr	α7 Nicotinic receptor-mediated astrocytic gliotransmitter release: Aβ effects in a preclinical Alzheimer's mouse model.
title_full_unstemmed	α7 Nicotinic receptor-mediated astrocytic gliotransmitter release: Aβ effects in a preclinical Alzheimer's mouse model.
title_sort	α7 nicotinic receptor-mediated astrocytic gliotransmitter release: aβ effects in a preclinical alzheimer's mouse model.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/12a024508b614209a9d942692f6b1074
work_keys_str_mv	AT tiinamariapirttimaki a7nicotinicreceptormediatedastrocyticgliotransmitterreleaseabeffectsinapreclinicalalzheimersmousemodel AT neelakrushnacodadu a7nicotinicreceptormediatedastrocyticgliotransmitterreleaseabeffectsinapreclinicalalzheimersmousemodel AT aliaawni a7nicotinicreceptormediatedastrocyticgliotransmitterreleaseabeffectsinapreclinicalalzheimersmousemodel AT pandeypratik a7nicotinicreceptormediatedastrocyticgliotransmitterreleaseabeffectsinapreclinicalalzheimersmousemodel AT davidandrewnagel a7nicotinicreceptormediatedastrocyticgliotransmitterreleaseabeffectsinapreclinicalalzheimersmousemodel AT ericjameshill a7nicotinicreceptormediatedastrocyticgliotransmitterreleaseabeffectsinapreclinicalalzheimersmousemodel AT kellytennysondineley a7nicotinicreceptormediatedastrocyticgliotransmitterreleaseabeffectsinapreclinicalalzheimersmousemodel AT hrheinalltparri a7nicotinicreceptormediatedastrocyticgliotransmitterreleaseabeffectsinapreclinicalalzheimersmousemodel
_version_	1718421365952872448

α7 Nicotinic receptor-mediated astrocytic gliotransmitter release: Aβ effects in a preclinical Alzheimer's mouse model.

Ejemplares similares