Dopaminergic dysfunction in the 3xTg-AD mice model of Alzheimer’s disease

Abstract Alzheimer’s disease (AD) is characterized by amyloid (Aβ) protein aggregation and neurofibrillary tangles accumulation, accompanied by neuroinflammation. With all the therapeutic attempts targeting these biomarkers having been unsuccessful, the understanding of early mechanisms involved in...

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Autores principales:	Yesica Gloria, Kelly Ceyzériat, Stergios Tsartsalis, Philippe Millet, Benjamin B. Tournier
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1fd7e2b173d64bf296cc67fcccdb9cd1
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spelling	oai:doaj.org-article:1fd7e2b173d64bf296cc67fcccdb9cd12021-12-02T17:37:29ZDopaminergic dysfunction in the 3xTg-AD mice model of Alzheimer’s disease10.1038/s41598-021-99025-12045-2322https://doaj.org/article/1fd7e2b173d64bf296cc67fcccdb9cd12021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-99025-1https://doaj.org/toc/2045-2322Abstract Alzheimer’s disease (AD) is characterized by amyloid (Aβ) protein aggregation and neurofibrillary tangles accumulation, accompanied by neuroinflammation. With all the therapeutic attempts targeting these biomarkers having been unsuccessful, the understanding of early mechanisms involved in the pathology is of paramount importance. Dopaminergic system involvement in AD has been suggested, particularly through the appearance of dopaminergic dysfunction-related neuropsychiatric symptoms and an overall worsening of cognitive and behavioral symptoms. In this study, we reported an early dopaminergic dysfunction in a mouse model presenting both amyloid and Tau pathology. 3xTg-AD mice showed an increase of postsynaptic D2/3R receptors density in the striatum and D2/3-autoreceptors in SN/VTA cell bodies. Functionally, a reduction of anxiety-like behavior, an increase in locomotor activity and D2R hyper-sensitivity to quinpirole stimulation have been observed. In addition, microglial cells in the striatum showed an early inflammatory response, suggesting its participation in dopaminergic alterations. These events are observed at an age when tau accumulation and Aβ deposits in the hippocampus are low. Thus, our results suggest that early dopaminergic dysfunction could have consequences in behavior and cognitive function, and may shed light on future therapeutic pathways of AD.Yesica GloriaKelly CeyzériatStergios TsartsalisPhilippe MilletBenjamin B. TournierNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yesica Gloria Kelly Ceyzériat Stergios Tsartsalis Philippe Millet Benjamin B. Tournier Dopaminergic dysfunction in the 3xTg-AD mice model of Alzheimer’s disease
description	Abstract Alzheimer’s disease (AD) is characterized by amyloid (Aβ) protein aggregation and neurofibrillary tangles accumulation, accompanied by neuroinflammation. With all the therapeutic attempts targeting these biomarkers having been unsuccessful, the understanding of early mechanisms involved in the pathology is of paramount importance. Dopaminergic system involvement in AD has been suggested, particularly through the appearance of dopaminergic dysfunction-related neuropsychiatric symptoms and an overall worsening of cognitive and behavioral symptoms. In this study, we reported an early dopaminergic dysfunction in a mouse model presenting both amyloid and Tau pathology. 3xTg-AD mice showed an increase of postsynaptic D2/3R receptors density in the striatum and D2/3-autoreceptors in SN/VTA cell bodies. Functionally, a reduction of anxiety-like behavior, an increase in locomotor activity and D2R hyper-sensitivity to quinpirole stimulation have been observed. In addition, microglial cells in the striatum showed an early inflammatory response, suggesting its participation in dopaminergic alterations. These events are observed at an age when tau accumulation and Aβ deposits in the hippocampus are low. Thus, our results suggest that early dopaminergic dysfunction could have consequences in behavior and cognitive function, and may shed light on future therapeutic pathways of AD.
format	article
author	Yesica Gloria Kelly Ceyzériat Stergios Tsartsalis Philippe Millet Benjamin B. Tournier
author_facet	Yesica Gloria Kelly Ceyzériat Stergios Tsartsalis Philippe Millet Benjamin B. Tournier
author_sort	Yesica Gloria
title	Dopaminergic dysfunction in the 3xTg-AD mice model of Alzheimer’s disease
title_short	Dopaminergic dysfunction in the 3xTg-AD mice model of Alzheimer’s disease
title_full	Dopaminergic dysfunction in the 3xTg-AD mice model of Alzheimer’s disease
title_fullStr	Dopaminergic dysfunction in the 3xTg-AD mice model of Alzheimer’s disease
title_full_unstemmed	Dopaminergic dysfunction in the 3xTg-AD mice model of Alzheimer’s disease
title_sort	dopaminergic dysfunction in the 3xtg-ad mice model of alzheimer’s disease
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/1fd7e2b173d64bf296cc67fcccdb9cd1
work_keys_str_mv	AT yesicagloria dopaminergicdysfunctioninthe3xtgadmicemodelofalzheimersdisease AT kellyceyzeriat dopaminergicdysfunctioninthe3xtgadmicemodelofalzheimersdisease AT stergiostsartsalis dopaminergicdysfunctioninthe3xtgadmicemodelofalzheimersdisease AT philippemillet dopaminergicdysfunctioninthe3xtgadmicemodelofalzheimersdisease AT benjaminbtournier dopaminergicdysfunctioninthe3xtgadmicemodelofalzheimersdisease
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Dopaminergic dysfunction in the 3xTg-AD mice model of Alzheimer’s disease

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