Cargando…
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...
Autores principales: | , , , , , |
---|---|
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 |
_version_ | 1784740480522649600 |
---|---|
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. |
format | Online Article Text |
id | pubmed-9253406 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT podlachamagdalena behavioralandbloodbasedbiomarkersforhuntingtonsdiseasestudiesonther61mousemodelwithprospectsforearlydiagnosisandmonitoringofthedisease AT pierzynowskakarolina behavioralandbloodbasedbiomarkersforhuntingtonsdiseasestudiesonther61mousemodelwithprospectsforearlydiagnosisandmonitoringofthedisease AT gaffkelidia behavioralandbloodbasedbiomarkersforhuntingtonsdiseasestudiesonther61mousemodelwithprospectsforearlydiagnosisandmonitoringofthedisease AT jerzemowskagrazyna behavioralandbloodbasedbiomarkersforhuntingtonsdiseasestudiesonther61mousemodelwithprospectsforearlydiagnosisandmonitoringofthedisease AT piotrowskaewa behavioralandbloodbasedbiomarkersforhuntingtonsdiseasestudiesonther61mousemodelwithprospectsforearlydiagnosisandmonitoringofthedisease AT wegrzyngrzegorz behavioralandbloodbasedbiomarkersforhuntingtonsdiseasestudiesonther61mousemodelwithprospectsforearlydiagnosisandmonitoringofthedisease |