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Behavioral- and blood-based biomarkers for Huntington's disease: Studies on the R6/1 mouse model with prospects for early diagnosis and monitoring of the disease

BACKGROUND: Huntington's disease (HD) is a genetic neurodegenerative disorder characterized by a triad of cognitive, psychiatric and motor symptoms. One of the main mechanisms of the disease, besides the aggregation of mutant proteins, is the chronic inflammation that occurs in patients long be...

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Autores principales: Podlacha, Magdalena, Pierzynowska, Karolina, Gaffke, Lidia, Jerzemowska, Grażyna, Piotrowska, Ewa, Węgrzyn, Grzegorz
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9253406/
https://www.ncbi.nlm.nih.gov/pubmed/35799674
http://dx.doi.org/10.1016/j.bbih.2022.100482
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author Podlacha, Magdalena
Pierzynowska, Karolina
Gaffke, Lidia
Jerzemowska, Grażyna
Piotrowska, Ewa
Węgrzyn, Grzegorz
author_facet Podlacha, Magdalena
Pierzynowska, Karolina
Gaffke, Lidia
Jerzemowska, Grażyna
Piotrowska, Ewa
Węgrzyn, Grzegorz
author_sort Podlacha, Magdalena
collection PubMed
description BACKGROUND: Huntington's disease (HD) is a genetic neurodegenerative disorder characterized by a triad of cognitive, psychiatric and motor symptoms. One of the main mechanisms of the disease, besides the aggregation of mutant proteins, is the chronic inflammation that occurs in patients long before the onset of motor dysfunction. Currently, no effective therapy is available for HD. As the progression of HD is usually slow and its first clinical manifestations are non-specific, a correct diagnosis is difficult. Moreover, any attempts to develop therapies for HD require monitoring of unequivocal markers of the disease which are also hardly available. OBJECTIVE: Using a mouse model of HD, we aimed to determine a battery of biomarkers in peripheral blood, as well as those related to cognitive or anxiety disturbances, corresponding to the most characteristic breakpoints in HD. METHODS: The R6/1 mouse line was used as an animal HD model. Levels of cytokines and hormones in blood were estimated by ELISA. A series of behavioral and movement tests was applied. RESULTS: Significant elevation of levels of specific inflammatory markers (IL-6, TNF-α, IL-1β, IL-12) was observed in the course of HD. At early stages of the disease, an impairment of anti-inflammatory defense mechanisms was evident, expressed by a significant decrease in IL-10 levels. The disturbances were faster in females than in males which might also translate into a potentially worse response to any administered drugs. Impaired memory and anxiety could be detected. CONCLUSION: A set of simple behavioral- and blood-based biomarkers for HD has been detected.
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spelling pubmed-92534062022-07-06 Behavioral- and blood-based biomarkers for Huntington's disease: Studies on the R6/1 mouse model with prospects for early diagnosis and monitoring of the disease Podlacha, Magdalena Pierzynowska, Karolina Gaffke, Lidia Jerzemowska, Grażyna Piotrowska, Ewa Węgrzyn, Grzegorz Brain Behav Immun Health Full Length Article BACKGROUND: Huntington's disease (HD) is a genetic neurodegenerative disorder characterized by a triad of cognitive, psychiatric and motor symptoms. One of the main mechanisms of the disease, besides the aggregation of mutant proteins, is the chronic inflammation that occurs in patients long before the onset of motor dysfunction. Currently, no effective therapy is available for HD. As the progression of HD is usually slow and its first clinical manifestations are non-specific, a correct diagnosis is difficult. Moreover, any attempts to develop therapies for HD require monitoring of unequivocal markers of the disease which are also hardly available. OBJECTIVE: Using a mouse model of HD, we aimed to determine a battery of biomarkers in peripheral blood, as well as those related to cognitive or anxiety disturbances, corresponding to the most characteristic breakpoints in HD. METHODS: The R6/1 mouse line was used as an animal HD model. Levels of cytokines and hormones in blood were estimated by ELISA. A series of behavioral and movement tests was applied. RESULTS: Significant elevation of levels of specific inflammatory markers (IL-6, TNF-α, IL-1β, IL-12) was observed in the course of HD. At early stages of the disease, an impairment of anti-inflammatory defense mechanisms was evident, expressed by a significant decrease in IL-10 levels. The disturbances were faster in females than in males which might also translate into a potentially worse response to any administered drugs. Impaired memory and anxiety could be detected. CONCLUSION: A set of simple behavioral- and blood-based biomarkers for HD has been detected. Elsevier 2022-06-23 /pmc/articles/PMC9253406/ /pubmed/35799674 http://dx.doi.org/10.1016/j.bbih.2022.100482 Text en © 2022 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Full Length Article
Podlacha, Magdalena
Pierzynowska, Karolina
Gaffke, Lidia
Jerzemowska, Grażyna
Piotrowska, Ewa
Węgrzyn, Grzegorz
Behavioral- and blood-based biomarkers for Huntington's disease: Studies on the R6/1 mouse model with prospects for early diagnosis and monitoring of the disease
title Behavioral- and blood-based biomarkers for Huntington's disease: Studies on the R6/1 mouse model with prospects for early diagnosis and monitoring of the disease
title_full Behavioral- and blood-based biomarkers for Huntington's disease: Studies on the R6/1 mouse model with prospects for early diagnosis and monitoring of the disease
title_fullStr Behavioral- and blood-based biomarkers for Huntington's disease: Studies on the R6/1 mouse model with prospects for early diagnosis and monitoring of the disease
title_full_unstemmed Behavioral- and blood-based biomarkers for Huntington's disease: Studies on the R6/1 mouse model with prospects for early diagnosis and monitoring of the disease
title_short Behavioral- and blood-based biomarkers for Huntington's disease: Studies on the R6/1 mouse model with prospects for early diagnosis and monitoring of the disease
title_sort behavioral- and blood-based biomarkers for huntington's disease: studies on the r6/1 mouse model with prospects for early diagnosis and monitoring of the disease
topic Full Length Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9253406/
https://www.ncbi.nlm.nih.gov/pubmed/35799674
http://dx.doi.org/10.1016/j.bbih.2022.100482
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