Andrographolide promotes hippocampal neurogenesis and spatial memory in the APPswe/PS1ΔE9 mouse model of Alzheimer’s disease

Abstract In Alzheimer´s disease (AD) there is a reduction in hippocampal neurogenesis that has been associated to cognitive deficits. Previously we showed that Andrographolide (ANDRO), the main bioactive component of Andrographis paniculate, induces proliferation in the hippocampus of the APPswe/PSE...

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Autores principales:	Sebastian B. Arredondo, Daniel T. Reyes, Andrea Herrera-Soto, Muriel D. Mardones, Nibaldo C. Inestrosa, Lorena Varela-Nallar
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ca4b966c21c9405888f78dead9baf1c9
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spelling	oai:doaj.org-article:ca4b966c21c9405888f78dead9baf1c92021-11-28T12:16:22ZAndrographolide promotes hippocampal neurogenesis and spatial memory in the APPswe/PS1ΔE9 mouse model of Alzheimer’s disease10.1038/s41598-021-01977-x2045-2322https://doaj.org/article/ca4b966c21c9405888f78dead9baf1c92021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-01977-xhttps://doaj.org/toc/2045-2322Abstract In Alzheimer´s disease (AD) there is a reduction in hippocampal neurogenesis that has been associated to cognitive deficits. Previously we showed that Andrographolide (ANDRO), the main bioactive component of Andrographis paniculate, induces proliferation in the hippocampus of the APPswe/PSEN1ΔE9 (APP/PS1) mouse model of AD as assessed by staining with the mitotic marker Ki67. Here, we further characterized the effect of ANDRO on hippocampal neurogenesis in APP/PS1 mice and evaluated the contribution of this process to the cognitive effect of ANDRO. Treatment of 8-month-old APP/PS1 mice with ANDRO for 4 weeks increased proliferation in the dentate gyrus as evaluated by BrdU incorporation. Although ANDRO had no effect on neuronal differentiation of newborn cells, it strongly increased neural progenitors, neuroblasts and newborn immature neurons, cell populations that were decreased in APP/PS1 mice compared to age-matched wild-type mice. ANDRO had no effect on migration or in total dendritic length, arborization and orientation of immature neurons, suggesting no effects on early morphological development of newborn neurons. Finally, ANDRO treatment improved the performance of APP/PS1 mice in the object location memory task. This effect was not completely prevented by co-treatment with the anti-mitotic drug TMZ, suggesting that other effects of ANDRO in addition to the increase in neurogenesis might underlie the observed cognitive improvement. Altogether, our data indicate that in APP/PS1 mice ANDRO stimulates neurogenesis in the hippocampus by inducing proliferation of neural precursor cells and improves spatial memory performance.Sebastian B. ArredondoDaniel T. ReyesAndrea Herrera-SotoMuriel D. MardonesNibaldo C. InestrosaLorena Varela-NallarNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sebastian B. Arredondo Daniel T. Reyes Andrea Herrera-Soto Muriel D. Mardones Nibaldo C. Inestrosa Lorena Varela-Nallar Andrographolide promotes hippocampal neurogenesis and spatial memory in the APPswe/PS1ΔE9 mouse model of Alzheimer’s disease
description	Abstract In Alzheimer´s disease (AD) there is a reduction in hippocampal neurogenesis that has been associated to cognitive deficits. Previously we showed that Andrographolide (ANDRO), the main bioactive component of Andrographis paniculate, induces proliferation in the hippocampus of the APPswe/PSEN1ΔE9 (APP/PS1) mouse model of AD as assessed by staining with the mitotic marker Ki67. Here, we further characterized the effect of ANDRO on hippocampal neurogenesis in APP/PS1 mice and evaluated the contribution of this process to the cognitive effect of ANDRO. Treatment of 8-month-old APP/PS1 mice with ANDRO for 4 weeks increased proliferation in the dentate gyrus as evaluated by BrdU incorporation. Although ANDRO had no effect on neuronal differentiation of newborn cells, it strongly increased neural progenitors, neuroblasts and newborn immature neurons, cell populations that were decreased in APP/PS1 mice compared to age-matched wild-type mice. ANDRO had no effect on migration or in total dendritic length, arborization and orientation of immature neurons, suggesting no effects on early morphological development of newborn neurons. Finally, ANDRO treatment improved the performance of APP/PS1 mice in the object location memory task. This effect was not completely prevented by co-treatment with the anti-mitotic drug TMZ, suggesting that other effects of ANDRO in addition to the increase in neurogenesis might underlie the observed cognitive improvement. Altogether, our data indicate that in APP/PS1 mice ANDRO stimulates neurogenesis in the hippocampus by inducing proliferation of neural precursor cells and improves spatial memory performance.
format	article
author	Sebastian B. Arredondo Daniel T. Reyes Andrea Herrera-Soto Muriel D. Mardones Nibaldo C. Inestrosa Lorena Varela-Nallar
author_facet	Sebastian B. Arredondo Daniel T. Reyes Andrea Herrera-Soto Muriel D. Mardones Nibaldo C. Inestrosa Lorena Varela-Nallar
author_sort	Sebastian B. Arredondo
title	Andrographolide promotes hippocampal neurogenesis and spatial memory in the APPswe/PS1ΔE9 mouse model of Alzheimer’s disease
title_short	Andrographolide promotes hippocampal neurogenesis and spatial memory in the APPswe/PS1ΔE9 mouse model of Alzheimer’s disease
title_full	Andrographolide promotes hippocampal neurogenesis and spatial memory in the APPswe/PS1ΔE9 mouse model of Alzheimer’s disease
title_fullStr	Andrographolide promotes hippocampal neurogenesis and spatial memory in the APPswe/PS1ΔE9 mouse model of Alzheimer’s disease
title_full_unstemmed	Andrographolide promotes hippocampal neurogenesis and spatial memory in the APPswe/PS1ΔE9 mouse model of Alzheimer’s disease
title_sort	andrographolide promotes hippocampal neurogenesis and spatial memory in the appswe/ps1δe9 mouse model of alzheimer’s disease
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/ca4b966c21c9405888f78dead9baf1c9
work_keys_str_mv	AT sebastianbarredondo andrographolidepromoteshippocampalneurogenesisandspatialmemoryintheappsweps1de9mousemodelofalzheimersdisease AT danieltreyes andrographolidepromoteshippocampalneurogenesisandspatialmemoryintheappsweps1de9mousemodelofalzheimersdisease AT andreaherrerasoto andrographolidepromoteshippocampalneurogenesisandspatialmemoryintheappsweps1de9mousemodelofalzheimersdisease AT murieldmardones andrographolidepromoteshippocampalneurogenesisandspatialmemoryintheappsweps1de9mousemodelofalzheimersdisease AT nibaldocinestrosa andrographolidepromoteshippocampalneurogenesisandspatialmemoryintheappsweps1de9mousemodelofalzheimersdisease AT lorenavarelanallar andrographolidepromoteshippocampalneurogenesisandspatialmemoryintheappsweps1de9mousemodelofalzheimersdisease
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Andrographolide promotes hippocampal neurogenesis and spatial memory in the APPswe/PS1ΔE9 mouse model of Alzheimer’s disease

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