Specific serotonergic denervation affects tau pathology and cognition without altering senile plaques deposition in APP/PS1 mice.

Senile plaques and neurofibrillary tangles are major neuropathological features of Alzheimer's Disease (AD), however neuronal loss is the alteration that best correlates with cognitive impairment in AD patients. Underlying neurotoxic mechanisms are not completely understood although specific ne...

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Autores principales:	Juan Jose Ramos-Rodriguez, Sara Molina-Gil, Raquel Rey-Brea, Esther Berrocoso, Monica Garcia-Alloza
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/aabe188cf7b946d3a9571c46294d97b0
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spelling	oai:doaj.org-article:aabe188cf7b946d3a9571c46294d97b02021-11-18T08:45:16ZSpecific serotonergic denervation affects tau pathology and cognition without altering senile plaques deposition in APP/PS1 mice.1932-620310.1371/journal.pone.0079947https://doaj.org/article/aabe188cf7b946d3a9571c46294d97b02013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24278223/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Senile plaques and neurofibrillary tangles are major neuropathological features of Alzheimer's Disease (AD), however neuronal loss is the alteration that best correlates with cognitive impairment in AD patients. Underlying neurotoxic mechanisms are not completely understood although specific neurotransmission deficiencies have been observed in AD patients and, in animal models, cholinergic and noradrenergic denervation may increase amyloid-beta deposition and tau phosphorylation in denervated areas. On the other hand brainstem neurodegeneration has been suggested as an initial event in AD, and serotonergic dysfunction, as well as reductions in raphe neurones density, have been reported in AD patients. In this study we addressed whether specific serotonergic denervation, by administering 5,7-dihydroxitriptamine (5,7-DHT) in the raphe nuclei, could also worsen central pathology in APPswe/PS1dE9 mice or interfere with learning and memory activities. In our hands specific serotonergic denervation increased tau phosphorylation in denervated cortex, without affecting amyloid-beta (Aβ) pathology. We also observed that APPswe/PS1dE9 mice lesioned with 5,7-DHT were impaired in the Morris water maze test, supporting a synergistic effect of the serotonergic denervation and the presence of APP/PS1 transgenes on learning and memory impairment. Altogether our data suggest that serotonergic denervation may interfere with some pathological aspects observed in AD, including tau phosphorylation or cognitive impairment, without affecting Aβ pathology, supporting a differential role of specific neurotransmitter systems in AD.Juan Jose Ramos-RodriguezSara Molina-GilRaquel Rey-BreaEsther BerrocosoMonica Garcia-AllozaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 11, p e79947 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Juan Jose Ramos-Rodriguez Sara Molina-Gil Raquel Rey-Brea Esther Berrocoso Monica Garcia-Alloza Specific serotonergic denervation affects tau pathology and cognition without altering senile plaques deposition in APP/PS1 mice.
description	Senile plaques and neurofibrillary tangles are major neuropathological features of Alzheimer's Disease (AD), however neuronal loss is the alteration that best correlates with cognitive impairment in AD patients. Underlying neurotoxic mechanisms are not completely understood although specific neurotransmission deficiencies have been observed in AD patients and, in animal models, cholinergic and noradrenergic denervation may increase amyloid-beta deposition and tau phosphorylation in denervated areas. On the other hand brainstem neurodegeneration has been suggested as an initial event in AD, and serotonergic dysfunction, as well as reductions in raphe neurones density, have been reported in AD patients. In this study we addressed whether specific serotonergic denervation, by administering 5,7-dihydroxitriptamine (5,7-DHT) in the raphe nuclei, could also worsen central pathology in APPswe/PS1dE9 mice or interfere with learning and memory activities. In our hands specific serotonergic denervation increased tau phosphorylation in denervated cortex, without affecting amyloid-beta (Aβ) pathology. We also observed that APPswe/PS1dE9 mice lesioned with 5,7-DHT were impaired in the Morris water maze test, supporting a synergistic effect of the serotonergic denervation and the presence of APP/PS1 transgenes on learning and memory impairment. Altogether our data suggest that serotonergic denervation may interfere with some pathological aspects observed in AD, including tau phosphorylation or cognitive impairment, without affecting Aβ pathology, supporting a differential role of specific neurotransmitter systems in AD.
format	article
author	Juan Jose Ramos-Rodriguez Sara Molina-Gil Raquel Rey-Brea Esther Berrocoso Monica Garcia-Alloza
author_facet	Juan Jose Ramos-Rodriguez Sara Molina-Gil Raquel Rey-Brea Esther Berrocoso Monica Garcia-Alloza
author_sort	Juan Jose Ramos-Rodriguez
title	Specific serotonergic denervation affects tau pathology and cognition without altering senile plaques deposition in APP/PS1 mice.
title_short	Specific serotonergic denervation affects tau pathology and cognition without altering senile plaques deposition in APP/PS1 mice.
title_full	Specific serotonergic denervation affects tau pathology and cognition without altering senile plaques deposition in APP/PS1 mice.
title_fullStr	Specific serotonergic denervation affects tau pathology and cognition without altering senile plaques deposition in APP/PS1 mice.
title_full_unstemmed	Specific serotonergic denervation affects tau pathology and cognition without altering senile plaques deposition in APP/PS1 mice.
title_sort	specific serotonergic denervation affects tau pathology and cognition without altering senile plaques deposition in app/ps1 mice.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/aabe188cf7b946d3a9571c46294d97b0
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Specific serotonergic denervation affects tau pathology and cognition without altering senile plaques deposition in APP/PS1 mice.

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