Changes in Day/Night Activity in the 6-OHDA-Induced Experimental Model of Parkinson's Disease: Exploring Prodromal Biomarkers

The search for experimental models mimicking an early stage of Parkinson's disease (PD) before motor manifestations is fundamental in order to explore early signs and get a better prognosis. Interestingly, our previous studies have indicated that 6-hydroxydopamine (6-OHDA) is a suitable model t...

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Published inFrontiers in neuroscience Vol. 14; p. 590029
Main Authors Requejo, Catalina, López-de-Ipiña, Karmele, Ruiz-Ortega, José Ángel, Fernández, Elsa, Calvo, Pilar M, Morera-Herreras, Teresa, Miguelez, Cristina, Cardona-Grifoll, Laura, Cepeda, Hodei, Ugedo, Luisa, Lafuente, José Vicente
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Research Foundation 14.10.2020
Frontiers Media S.A
Subjects
6-Hydroxydopamine
Amphetamines
Apoptosis
behavior
Biomarkers
Circadian rhythm
Circadian rhythms
Degeneration
Dopamine
Enrichment
home-cage monitoring system
Hydroxylase
Hyperactivity
Immunohistochemistry
Laboratory animals
Mimicry
Movement disorders
Neostriatum
Neurodegenerative diseases
Neuroprotection
Neuroscience
Parkinson's disease
prodromal biomarkers
prodromal Parkinson’s disease symptoms
Rodents
Sleep
Tyrosine 3-monooxygenase
United Kingdom > UK
United States > US
Spain
home-cage monitoring system
6-hydroxydopamine
rat
prodromal biomarkers
non-motor deficits
prodromal Parkinson’s disease symptoms
behavior
circadian rhythms
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Abstract The search for experimental models mimicking an early stage of Parkinson's disease (PD) before motor manifestations is fundamental in order to explore early signs and get a better prognosis. Interestingly, our previous studies have indicated that 6-hydroxydopamine (6-OHDA) is a suitable model to induce an early degeneration of the nigrostriatal system without any gross motor impairment. Considering our previous findings, we aim to implement a novel system to monitor rats after intrastriatal injection of 6-OHDA to detect and analyze physiological changes underlying prodromal PD. Twenty male Sprague-Dawley rats were unilaterally injected with 6-OHDA ( = 10) or saline solution ( = 10) into the right striatum and placed in enriched environment cages where the activity was monitored. After 2 weeks, the amphetamine test was performed before the sacrifice. Immunohistochemistry was developed for the morphological evaluation and western blot analysis to assess molecular changes. Home-cage monitoring revealed behavioral changes in response to 6-OHDA administration including significant hyperactivity and hypoactivity during the light and dark phase, respectively, turning out in a change of the circadian timing. A preclinical stage of PD was functionally confirmed with the amphetamine test. Moreover, the loss of tyrosine hydroxylase expression was significantly correlated with the motor results, and 6-OHDA induced early proapoptotic events. Our findings provide evidence for a novel prodromal 6-OHDA model following a customized monitoring system that could give insights to detect non-motor deficits and molecular targets to test neuroprotective/neurorestorative agents.
AbstractList The search for experimental models mimicking an early stage of Parkinson's disease (PD) before motor manifestations is fundamental in order to explore early signs and get a better prognosis. Interestingly, our previous studies have indicated that 6-hydroxydopamine (6-OHDA) is a suitable model to induce an early degeneration of the nigrostriatal system without any gross motor impairment. Considering our previous findings, we aim to implement a novel system to monitor rats after intrastriatal injection of 6-OHDA to detect and analyze physiological changes underlying prodromal PD. Twenty male Sprague-Dawley rats were unilaterally injected with 6-OHDA ( = 10) or saline solution ( = 10) into the right striatum and placed in enriched environment cages where the activity was monitored. After 2 weeks, the amphetamine test was performed before the sacrifice. Immunohistochemistry was developed for the morphological evaluation and western blot analysis to assess molecular changes. Home-cage monitoring revealed behavioral changes in response to 6-OHDA administration including significant hyperactivity and hypoactivity during the light and dark phase, respectively, turning out in a change of the circadian timing. A preclinical stage of PD was functionally confirmed with the amphetamine test. Moreover, the loss of tyrosine hydroxylase expression was significantly correlated with the motor results, and 6-OHDA induced early proapoptotic events. Our findings provide evidence for a novel prodromal 6-OHDA model following a customized monitoring system that could give insights to detect non-motor deficits and molecular targets to test neuroprotective/neurorestorative agents.
The search for experimental models mimicking an early stage of Parkinson’s disease (PD) before motor manifestations is fundamental in order to explore early signs and get a better prognosis. Interestingly, our previous studies have indicated that 6-hydroxydopamine (6-OHDA) is a suitable model to induce an early degeneration of the nigrostriatal system without any gross motor impairment. Considering our previous findings, we aim to implement a novel system to monitor rats after intrastriatal injection of 6-OHDA to detect and analyze physiological changes underlying prodromal PD. Twenty male Sprague-Dawley rats were unilaterally injected with 6-OHDA (n = 10) or saline solution (n = 10) into the right striatum and placed in enriched environment cages where the activity was monitored. After 2 weeks, the amphetamine test was performed before the sacrifice. Immunohistochemistry was developed for the morphological evaluation and western blot analysis to assess molecular changes. Home-cage monitoring revealed behavioral changes in response to 6-OHDA administration including significant hyperactivity and hypoactivity during the light and dark phase, respectively, turning out in a change of the circadian timing. A preclinical stage of PD was functionally confirmed with the amphetamine test. Moreover, the loss of tyrosine hydroxylase expression was significantly correlated with the motor results, and 6-OHDA induced early proapoptotic events. Our findings provide evidence for a novel prodromal 6-OHDA model following a customized monitoring system that could give insights to detect non-motor deficits and molecular targets to test neuroprotective/neurorestorative agents.
The search for experimental models mimicking an early stage of Parkinson’s disease (PD) before motor manifestations is fundamental in order to explore early signs and get a better prognosis. Interestingly, our previous studies have indicated that 6-hydroxydopamine (6-OHDA) is a suitable model to induce an early degeneration of the nigrostriatal system without any gross motor impairment. Considering our previous findings, we aim to implement a novel system to monitor rats after intrastriatal injection of 6-OHDA to detect and analyze physiological changes underlying prodromal PD. Twenty male Sprague-Dawley rats were unilaterally injected with 6-OHDA ( n = 10) or saline solution ( n = 10) into the right striatum and placed in enriched environment cages where the activity was monitored. After 2 weeks, the amphetamine test was performed before the sacrifice. Immunohistochemistry was developed for the morphological evaluation and western blot analysis to assess molecular changes. Home-cage monitoring revealed behavioral changes in response to 6-OHDA administration including significant hyperactivity and hypoactivity during the light and dark phase, respectively, turning out in a change of the circadian timing. A preclinical stage of PD was functionally confirmed with the amphetamine test. Moreover, the loss of tyrosine hydroxylase expression was significantly correlated with the motor results, and 6-OHDA induced early proapoptotic events. Our findings provide evidence for a novel prodromal 6-OHDA model following a customized monitoring system that could give insights to detect non-motor deficits and molecular targets to test neuroprotective/neurorestorative agents.
The search for experimental models mimicking an early stage of Parkinson´s disease (PD) before motor manifestations is fundamental in order to explore early signs and get a better prognosis. Interestingly, our previous studies have indicated that 6-hydroxydopamine (6-OHDA) is a suitable model to induce an early degeneration of the nigrostriatal system without any gross motor impairment. Considering our previous findings, we aim to implement a novel system to monitor rats after intrastriatal injection of 6-OHDA to detect and analyze physiological changes underlying prodromal PD. Twenty male Sprague-Dawley rats were unilaterally injected with 6-OHDA (n=10) or saline solution (n=10) into the right striatum and placed in enriched environment cages where the activity was monitored. After two weeks, the amphetamine test was performed before the sacrifice. Immunohistochemistry was developed for the morphological evaluation and western blot analysis to assess molecular changes. Home-cage monitoring revealed behavioral changes in response to 6-OHDA administration including significant hyperactivity and hypoactivity during the light and dark phase respectively turning out in a change of the circadian timing. A preclinical stage of PD was functionally confirmed with the amphetamine test. Moreover, the loss of tyrosine hydroxylase expression was significantly correlated with the motor results, and 6-OHDA induced early proapoptotic events. Our findings provide evidence for a novel prodromal 6-OHDA model following a customized monitoring system that could give insights to detect non-motor deficits and molecular targets to test neuroprotective/neurorestorative agents.
Author Morera-Herreras, Teresa
Miguelez, Cristina
Cepeda, Hodei
Ugedo, Luisa
Requejo, Catalina
Lafuente, José Vicente
Ruiz-Ortega, José Ángel
Fernández, Elsa
Calvo, Pilar M
López-de-Ipiña, Karmele
Cardona-Grifoll, Laura
AuthorAffiliation 3 EleKin Research Group, Department of Systems Engineering and Automation, University of the Basque Country (UPV/EHU) , Donostia , Spain
6 Autonomic and Movement Disorders Unit, Neurodegenerative diseases, Biocruces Health Research Institute , Barakaldo , Spain
1 LaNCE, Department of Neuroscience, University of the Basque Country (UPV/EHU) , Leioa , Spain
5 Department of Pharmacology, University of the Basque Country (UPV/EHU) , Leioa , Spain
2 Department of Neurology, Icahn School of Medicine at Mount Sinai, The Friedman Brain Institute, New York , NY , United States
4 Department of Psychiatry, University of Cambridge , Cambridge , United Kingdom
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Copyright Copyright © 2020 Requejo, López-de-Ipiña, Ruiz-Ortega, Fernández, Calvo, Morera-Herreras, Miguelez, Cardona-Grifoll, Cepeda, Ugedo and Lafuente.
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Copyright © 2020 Requejo, López-de-Ipiña, Ruiz-Ortega, Fernández, Calvo, Morera-Herreras, Miguelez, Cardona-Grifoll, Cepeda, Ugedo and Lafuente. 2020 Requejo, López-de-Ipiña, Ruiz-Ortega, Fernández, Calvo, Morera-Herreras, Miguelez, Cardona-Grifoll, Cepeda, Ugedo and Lafuente
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Keywords home-cage monitoring system
6-hydroxydopamine
rat
prodromal biomarkers
non-motor deficits
prodromal Parkinson’s disease symptoms
behavior
circadian rhythms
Language English
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Reviewed by: Andreas Wree, University of Rostock, Germany; Veronica Alexandra Antipova, Medical University of Graz, Austria; Alexander Hawlitschka, University Hospital Rostock, Germany
Edited by: Martin Witt, Centre of Transdisciplinary Neuroscience Rostock, Germany
This article was submitted to Neurodegeneration, a section of the journal Frontiers in Neuroscience
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Snippet The search for experimental models mimicking an early stage of Parkinson's disease (PD) before motor manifestations is fundamental in order to explore early...
The search for experimental models mimicking an early stage of Parkinson´s disease (PD) before motor manifestations is fundamental in order to explore early...
The search for experimental models mimicking an early stage of Parkinson’s disease (PD) before motor manifestations is fundamental in order to explore early...
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StartPage 590029
SubjectTerms 6-Hydroxydopamine
Amphetamines
Apoptosis
behavior
Biomarkers
Circadian rhythm
Circadian rhythms
Degeneration
Dopamine
Enrichment
home-cage monitoring system
Hydroxylase
Hyperactivity
Immunohistochemistry
Laboratory animals
Mimicry
Movement disorders
Neostriatum
Neurodegenerative diseases
Neuroprotection
Neuroscience
Parkinson's disease
prodromal biomarkers
prodromal Parkinson’s disease symptoms
Rodents
Sleep
Tyrosine 3-monooxygenase
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Title Changes in Day/Night Activity in the 6-OHDA-Induced Experimental Model of Parkinson's Disease: Exploring Prodromal Biomarkers
URI https://www.ncbi.nlm.nih.gov/pubmed/33154717
https://www.proquest.com/docview/2450874863
https://search.proquest.com/docview/2458036875
https://pubmed.ncbi.nlm.nih.gov/PMC7591774
https://doaj.org/article/4b743bd7fcb74f268e9906b6ad7a308a
Volume 14
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