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Mechanism underlying the effects of doxepin on β-amyloid -induced memory impairment in rats

OBJECTIVE(S): In previous studies, researchers observed that doxepin could improve cognitive processes and has protective effects on the central nervous system. Thus, this study was designed to analyze the effects of doxepin on β-amyloid (Aβ)-induced memory impairment and neuronal toxicity in rat an...

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Autores principales: Bu, Jimei, Zu, Hengbing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Mashhad University of Medical Sciences 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5651458/
https://www.ncbi.nlm.nih.gov/pubmed/29085600
http://dx.doi.org/10.22038/IJBMS.2017.9274
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author Bu, Jimei
Zu, Hengbing
author_facet Bu, Jimei
Zu, Hengbing
author_sort Bu, Jimei
collection PubMed
description OBJECTIVE(S): In previous studies, researchers observed that doxepin could improve cognitive processes and has protective effects on the central nervous system. Thus, this study was designed to analyze the effects of doxepin on β-amyloid (Aβ)-induced memory impairment and neuronal toxicity in rat and to explore the underlying mechanism. MATERIALS AND METHODS: Rats were treated with Aβ1-42 and doxepin was injected to validate its effects on cognitive function. The Morris water maze test was performed to detect memory function. Aβ1-42-treated SH-SY5Y human neuroblastoma cell line was also used to detect the effects of doxepin and to explore the underlying mechanism. Western blotting analysis was used to detect the protein expression levels of PSD-95, synapsin 1, p-AKT and p-mTOR in rats. RESULTS: After treated with 1 mg/kg of doxepin, Aβ1-42-treated rats showed markedly lower escape latency and higher platform-finding strategy score. Low doses of doxepin significantly reversed the effects of Aβ1-42 on the protein expression levels of PSD-95, synapsin 1, p-AKT and p-mTOR in rats. In vitro experiment showed the consistent results. Besides, PI3K inhibitor (LY294002) treatment could markedly reversed the effects of doxepin on Aβ1-42-treated SH-SY5Y cells. CONCLUSION: Our results demonstrated that doxepin could protect against the Aβ1-42-induced memory impairment in rats. The protective effect of doxepin was associated with the enhancement of PSD-95 and synapsin 1 expression via PI3K/AKT/mTOR signaling pathway.
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spelling pubmed-56514582017-10-30 Mechanism underlying the effects of doxepin on β-amyloid -induced memory impairment in rats Bu, Jimei Zu, Hengbing Iran J Basic Med Sci Original Article OBJECTIVE(S): In previous studies, researchers observed that doxepin could improve cognitive processes and has protective effects on the central nervous system. Thus, this study was designed to analyze the effects of doxepin on β-amyloid (Aβ)-induced memory impairment and neuronal toxicity in rat and to explore the underlying mechanism. MATERIALS AND METHODS: Rats were treated with Aβ1-42 and doxepin was injected to validate its effects on cognitive function. The Morris water maze test was performed to detect memory function. Aβ1-42-treated SH-SY5Y human neuroblastoma cell line was also used to detect the effects of doxepin and to explore the underlying mechanism. Western blotting analysis was used to detect the protein expression levels of PSD-95, synapsin 1, p-AKT and p-mTOR in rats. RESULTS: After treated with 1 mg/kg of doxepin, Aβ1-42-treated rats showed markedly lower escape latency and higher platform-finding strategy score. Low doses of doxepin significantly reversed the effects of Aβ1-42 on the protein expression levels of PSD-95, synapsin 1, p-AKT and p-mTOR in rats. In vitro experiment showed the consistent results. Besides, PI3K inhibitor (LY294002) treatment could markedly reversed the effects of doxepin on Aβ1-42-treated SH-SY5Y cells. CONCLUSION: Our results demonstrated that doxepin could protect against the Aβ1-42-induced memory impairment in rats. The protective effect of doxepin was associated with the enhancement of PSD-95 and synapsin 1 expression via PI3K/AKT/mTOR signaling pathway. Mashhad University of Medical Sciences 2017-09 /pmc/articles/PMC5651458/ /pubmed/29085600 http://dx.doi.org/10.22038/IJBMS.2017.9274 Text en Copyright: © Iranian Journal of Basic Medical Sciences http://creativecommons.org/licenses/by-nc-sa/3.0 This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Bu, Jimei
Zu, Hengbing
Mechanism underlying the effects of doxepin on β-amyloid -induced memory impairment in rats
title Mechanism underlying the effects of doxepin on β-amyloid -induced memory impairment in rats
title_full Mechanism underlying the effects of doxepin on β-amyloid -induced memory impairment in rats
title_fullStr Mechanism underlying the effects of doxepin on β-amyloid -induced memory impairment in rats
title_full_unstemmed Mechanism underlying the effects of doxepin on β-amyloid -induced memory impairment in rats
title_short Mechanism underlying the effects of doxepin on β-amyloid -induced memory impairment in rats
title_sort mechanism underlying the effects of doxepin on β-amyloid -induced memory impairment in rats
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5651458/
https://www.ncbi.nlm.nih.gov/pubmed/29085600
http://dx.doi.org/10.22038/IJBMS.2017.9274
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