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Administration of NaHS Attenuates Footshock-Induced Pathologies and Emotional and Cognitive Dysfunction in Triple Transgenic Alzheimer’s Mice

Alzheimer’s disease (AD) is characterized by progressive cognitive decline and neuropsychiatric symptoms. Increasing evidence indicates that environmental risk factors in young adults may accelerate cognitive loss in AD and that Hydrogen Sulfide (H(2)S) may represent an innovative treatment to slow...

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Autores principales: Huang, Hei-Jen, Chen, Shu-Ling, Hsieh-Li, Hsiu Mei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4658416/
https://www.ncbi.nlm.nih.gov/pubmed/26635562
http://dx.doi.org/10.3389/fnbeh.2015.00312
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author Huang, Hei-Jen
Chen, Shu-Ling
Hsieh-Li, Hsiu Mei
author_facet Huang, Hei-Jen
Chen, Shu-Ling
Hsieh-Li, Hsiu Mei
author_sort Huang, Hei-Jen
collection PubMed
description Alzheimer’s disease (AD) is characterized by progressive cognitive decline and neuropsychiatric symptoms. Increasing evidence indicates that environmental risk factors in young adults may accelerate cognitive loss in AD and that Hydrogen Sulfide (H(2)S) may represent an innovative treatment to slow the progression of AD. Therefore, the aim of this study was to evaluate the effects of NaHS, an H(2)S donor, in a triple transgenic AD mouse model (3×Tg-AD) under footshock with situational reminders (SRs). Inescapable footshock with SRs induced anxiety and cognitive dysfunction as well as a decrease in the levels of plasma H(2)S and GSH and an increase in IL-6 levels in 3×Tg-AD mice. Under footshock with SR stimulus, amyloid deposition, tau protein hyperphosphorylation, and microgliosis were highly increased in the stress-responsive brain structures, including the hippocampus and amygdala, of the AD mice. Oxidative stress, inflammatory response, and β-site APP cleaving enzyme 1 (BACE1) levels were also increased, and the level of inactivated glycogen synthase kinase-3β (GSK3β) (pSer9) was decreased in the hippocampi of AD mice subjected to footshock with SRs. Furthermore, the numbers of cholinergic neurons in the medial septum/diagonal band of Broca (MS/DB) and noradrenergic neurons in the locus coeruleus (LC) were also decreased in the 3×Tg-AD mice under footshock with SRs. These biochemical hallmarks and pathological presentations were all alleviated by the semi-acute administration of NaHS in the AD mice. Together, these findings suggest that footshock with SRs induces the impairment of spatial cognition and emotion, which involve pathological changes in the peripheral and central systems, including the hippocampus, MS/DB, LC, and BLA, and that the administration of NaHS may be a candidate strategy to ameliorate the progression of neurodegeneration.
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spelling pubmed-46584162015-12-03 Administration of NaHS Attenuates Footshock-Induced Pathologies and Emotional and Cognitive Dysfunction in Triple Transgenic Alzheimer’s Mice Huang, Hei-Jen Chen, Shu-Ling Hsieh-Li, Hsiu Mei Front Behav Neurosci Neuroscience Alzheimer’s disease (AD) is characterized by progressive cognitive decline and neuropsychiatric symptoms. Increasing evidence indicates that environmental risk factors in young adults may accelerate cognitive loss in AD and that Hydrogen Sulfide (H(2)S) may represent an innovative treatment to slow the progression of AD. Therefore, the aim of this study was to evaluate the effects of NaHS, an H(2)S donor, in a triple transgenic AD mouse model (3×Tg-AD) under footshock with situational reminders (SRs). Inescapable footshock with SRs induced anxiety and cognitive dysfunction as well as a decrease in the levels of plasma H(2)S and GSH and an increase in IL-6 levels in 3×Tg-AD mice. Under footshock with SR stimulus, amyloid deposition, tau protein hyperphosphorylation, and microgliosis were highly increased in the stress-responsive brain structures, including the hippocampus and amygdala, of the AD mice. Oxidative stress, inflammatory response, and β-site APP cleaving enzyme 1 (BACE1) levels were also increased, and the level of inactivated glycogen synthase kinase-3β (GSK3β) (pSer9) was decreased in the hippocampi of AD mice subjected to footshock with SRs. Furthermore, the numbers of cholinergic neurons in the medial septum/diagonal band of Broca (MS/DB) and noradrenergic neurons in the locus coeruleus (LC) were also decreased in the 3×Tg-AD mice under footshock with SRs. These biochemical hallmarks and pathological presentations were all alleviated by the semi-acute administration of NaHS in the AD mice. Together, these findings suggest that footshock with SRs induces the impairment of spatial cognition and emotion, which involve pathological changes in the peripheral and central systems, including the hippocampus, MS/DB, LC, and BLA, and that the administration of NaHS may be a candidate strategy to ameliorate the progression of neurodegeneration. Frontiers Media S.A. 2015-11-25 /pmc/articles/PMC4658416/ /pubmed/26635562 http://dx.doi.org/10.3389/fnbeh.2015.00312 Text en Copyright © 2015 Huang, Chen and Hsieh-Li. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution and reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Huang, Hei-Jen
Chen, Shu-Ling
Hsieh-Li, Hsiu Mei
Administration of NaHS Attenuates Footshock-Induced Pathologies and Emotional and Cognitive Dysfunction in Triple Transgenic Alzheimer’s Mice
title Administration of NaHS Attenuates Footshock-Induced Pathologies and Emotional and Cognitive Dysfunction in Triple Transgenic Alzheimer’s Mice
title_full Administration of NaHS Attenuates Footshock-Induced Pathologies and Emotional and Cognitive Dysfunction in Triple Transgenic Alzheimer’s Mice
title_fullStr Administration of NaHS Attenuates Footshock-Induced Pathologies and Emotional and Cognitive Dysfunction in Triple Transgenic Alzheimer’s Mice
title_full_unstemmed Administration of NaHS Attenuates Footshock-Induced Pathologies and Emotional and Cognitive Dysfunction in Triple Transgenic Alzheimer’s Mice
title_short Administration of NaHS Attenuates Footshock-Induced Pathologies and Emotional and Cognitive Dysfunction in Triple Transgenic Alzheimer’s Mice
title_sort administration of nahs attenuates footshock-induced pathologies and emotional and cognitive dysfunction in triple transgenic alzheimer’s mice
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4658416/
https://www.ncbi.nlm.nih.gov/pubmed/26635562
http://dx.doi.org/10.3389/fnbeh.2015.00312
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