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The histamine H3 receptor antagonist thioperamide rescues circadian rhythm and memory function in experimental parkinsonism

Parkinson's disease (PD) is a common neurodegenerative disorder, characterized by motor impairment and a wide range of non-motor symptoms, including sleep disorders and cognitive and affective deficits. In this study, we used a mouse model of PD based on 6-hydroxydopamine (6-OHDA) to examine th...

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Autores principales: Masini, D, Lopes-Aguiar, C, Bonito-Oliva, A, Papadia, D, Andersson, R, Fisahn, A, Fisone, G
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5416699/
https://www.ncbi.nlm.nih.gov/pubmed/28398338
http://dx.doi.org/10.1038/tp.2017.58
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author Masini, D
Lopes-Aguiar, C
Bonito-Oliva, A
Papadia, D
Andersson, R
Fisahn, A
Fisone, G
author_facet Masini, D
Lopes-Aguiar, C
Bonito-Oliva, A
Papadia, D
Andersson, R
Fisahn, A
Fisone, G
author_sort Masini, D
collection PubMed
description Parkinson's disease (PD) is a common neurodegenerative disorder, characterized by motor impairment and a wide range of non-motor symptoms, including sleep disorders and cognitive and affective deficits. In this study, we used a mouse model of PD based on 6-hydroxydopamine (6-OHDA) to examine the effect of thioperamide, a histamine H3 receptor antagonist, on circadian activity, recognition memory and anxiety. A partial, bilateral 6-OHDA lesion of the striatum reduces motor activity during the active phase of the 24 h cycle. In addition, the lesion disrupts the endogenous circadian rhythm observed when mice are maintained in constant darkness. Administration of thioperamide to 6-OHDA-lesion mice rescues the normal rest/activity cycle. Moreover, thioperamide counteracts the deficit of novel object recognition produced by 6-OHDA. Our experiments show that this memory impairment is accompanied by disrupted gamma oscillations in the hippocampus, which are also rescued by thioperamide. In contrast, we do not observe any modification of the anxiogenic effect of 6-OHDA in response to administration of thioperamide. Our results indicate that thioperamide may act as a multifunctional drug, able to counteract disruptions of circadian rhythm and cognitive deficits associated with PD.
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spelling pubmed-54166992017-05-16 The histamine H3 receptor antagonist thioperamide rescues circadian rhythm and memory function in experimental parkinsonism Masini, D Lopes-Aguiar, C Bonito-Oliva, A Papadia, D Andersson, R Fisahn, A Fisone, G Transl Psychiatry Original Article Parkinson's disease (PD) is a common neurodegenerative disorder, characterized by motor impairment and a wide range of non-motor symptoms, including sleep disorders and cognitive and affective deficits. In this study, we used a mouse model of PD based on 6-hydroxydopamine (6-OHDA) to examine the effect of thioperamide, a histamine H3 receptor antagonist, on circadian activity, recognition memory and anxiety. A partial, bilateral 6-OHDA lesion of the striatum reduces motor activity during the active phase of the 24 h cycle. In addition, the lesion disrupts the endogenous circadian rhythm observed when mice are maintained in constant darkness. Administration of thioperamide to 6-OHDA-lesion mice rescues the normal rest/activity cycle. Moreover, thioperamide counteracts the deficit of novel object recognition produced by 6-OHDA. Our experiments show that this memory impairment is accompanied by disrupted gamma oscillations in the hippocampus, which are also rescued by thioperamide. In contrast, we do not observe any modification of the anxiogenic effect of 6-OHDA in response to administration of thioperamide. Our results indicate that thioperamide may act as a multifunctional drug, able to counteract disruptions of circadian rhythm and cognitive deficits associated with PD. Nature Publishing Group 2017-04 2017-04-11 /pmc/articles/PMC5416699/ /pubmed/28398338 http://dx.doi.org/10.1038/tp.2017.58 Text en Copyright © 2017 The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Original Article
Masini, D
Lopes-Aguiar, C
Bonito-Oliva, A
Papadia, D
Andersson, R
Fisahn, A
Fisone, G
The histamine H3 receptor antagonist thioperamide rescues circadian rhythm and memory function in experimental parkinsonism
title The histamine H3 receptor antagonist thioperamide rescues circadian rhythm and memory function in experimental parkinsonism
title_full The histamine H3 receptor antagonist thioperamide rescues circadian rhythm and memory function in experimental parkinsonism
title_fullStr The histamine H3 receptor antagonist thioperamide rescues circadian rhythm and memory function in experimental parkinsonism
title_full_unstemmed The histamine H3 receptor antagonist thioperamide rescues circadian rhythm and memory function in experimental parkinsonism
title_short The histamine H3 receptor antagonist thioperamide rescues circadian rhythm and memory function in experimental parkinsonism
title_sort histamine h3 receptor antagonist thioperamide rescues circadian rhythm and memory function in experimental parkinsonism
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5416699/
https://www.ncbi.nlm.nih.gov/pubmed/28398338
http://dx.doi.org/10.1038/tp.2017.58
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