Unilateral Intrastriatal 6-Hydroxydopamine Lesion in Mice: A Closer Look into Non-Motor Phenotype and Glial Response

Parkinson’s disease (PD) is a prevalent movement disorder characterized by the progressive loss of dopaminergic neurons in substantia nigra pars compacta (SNpc). The 6-hydroxydopamine (6-OHDA) lesion is still one of the most widely used techniques for modeling Parkinson’s disease (PD) in rodents. De...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Bárbara Mendes-Pinheiro, Carina Soares-Cunha, Ana Marote, Eduardo Loureiro-Campos, Jonas Campos, Sandra Barata-Antunes, Daniela Monteiro-Fernandes, Diogo Santos, Sara Duarte-Silva, Luísa Pinto, António José Salgado
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	Parkinson’s disease 6-OHDA unilateral striatum dopaminergic degeneration motor behavior Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/5b7bfaea66c64604aa2a882f0e19aabe
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:5b7bfaea66c64604aa2a882f0e19aabe
record_format	dspace
spelling	oai:doaj.org-article:5b7bfaea66c64604aa2a882f0e19aabe2021-11-11T16:59:37ZUnilateral Intrastriatal 6-Hydroxydopamine Lesion in Mice: A Closer Look into Non-Motor Phenotype and Glial Response10.3390/ijms2221115301422-00671661-6596https://doaj.org/article/5b7bfaea66c64604aa2a882f0e19aabe2021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11530https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Parkinson’s disease (PD) is a prevalent movement disorder characterized by the progressive loss of dopaminergic neurons in substantia nigra pars compacta (SNpc). The 6-hydroxydopamine (6-OHDA) lesion is still one of the most widely used techniques for modeling Parkinson’s disease (PD) in rodents. Despite commonly used in rats, it can be challenging to reproduce a similar lesion in mice. Moreover, there is a lack of characterization of the extent of behavioral deficits and of the neuronal loss/neurotransmitter system in unilateral lesion mouse models. In this study, we present an extensive behavioral and histological characterization of a unilateral intrastriatal 6-OHDA mouse model. Our results indicate significant alterations in balance and fine motor coordination, voluntary locomotion, and in the asymmetry’s degree of forelimb use in 6-OHDA lesioned animals, accompanied by a decrease in self-care and motivational behavior, common features of depressive-like symptomatology. These results were accompanied by a decrease in tyrosine hydroxylase (TH)-labelling and dopamine levels within the nigrostriatal pathway. Additionally, we also identify a marked astrocytic reaction, as well as proliferative and reactive microglia in lesioned areas. These results confirm the use of unilateral intrastriatal 6-OHDA mice for the generation of a mild model of nigrostriatal degeneration and further evidences the recapitulation of key aspects of PD, thereby being suitable for future studies beholding new therapeutical interventions for this disease.Bárbara Mendes-PinheiroCarina Soares-CunhaAna MaroteEduardo Loureiro-CamposJonas CamposSandra Barata-AntunesDaniela Monteiro-FernandesDiogo SantosSara Duarte-SilvaLuísa PintoAntónio José SalgadoMDPI AGarticleParkinson’s disease6-OHDAunilateralstriatumdopaminergic degenerationmotor behaviorBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11530, p 11530 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Parkinson’s disease 6-OHDA unilateral striatum dopaminergic degeneration motor behavior Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	Parkinson’s disease 6-OHDA unilateral striatum dopaminergic degeneration motor behavior Biology (General) QH301-705.5 Chemistry QD1-999 Bárbara Mendes-Pinheiro Carina Soares-Cunha Ana Marote Eduardo Loureiro-Campos Jonas Campos Sandra Barata-Antunes Daniela Monteiro-Fernandes Diogo Santos Sara Duarte-Silva Luísa Pinto António José Salgado Unilateral Intrastriatal 6-Hydroxydopamine Lesion in Mice: A Closer Look into Non-Motor Phenotype and Glial Response
description	Parkinson’s disease (PD) is a prevalent movement disorder characterized by the progressive loss of dopaminergic neurons in substantia nigra pars compacta (SNpc). The 6-hydroxydopamine (6-OHDA) lesion is still one of the most widely used techniques for modeling Parkinson’s disease (PD) in rodents. Despite commonly used in rats, it can be challenging to reproduce a similar lesion in mice. Moreover, there is a lack of characterization of the extent of behavioral deficits and of the neuronal loss/neurotransmitter system in unilateral lesion mouse models. In this study, we present an extensive behavioral and histological characterization of a unilateral intrastriatal 6-OHDA mouse model. Our results indicate significant alterations in balance and fine motor coordination, voluntary locomotion, and in the asymmetry’s degree of forelimb use in 6-OHDA lesioned animals, accompanied by a decrease in self-care and motivational behavior, common features of depressive-like symptomatology. These results were accompanied by a decrease in tyrosine hydroxylase (TH)-labelling and dopamine levels within the nigrostriatal pathway. Additionally, we also identify a marked astrocytic reaction, as well as proliferative and reactive microglia in lesioned areas. These results confirm the use of unilateral intrastriatal 6-OHDA mice for the generation of a mild model of nigrostriatal degeneration and further evidences the recapitulation of key aspects of PD, thereby being suitable for future studies beholding new therapeutical interventions for this disease.
format	article
author	Bárbara Mendes-Pinheiro Carina Soares-Cunha Ana Marote Eduardo Loureiro-Campos Jonas Campos Sandra Barata-Antunes Daniela Monteiro-Fernandes Diogo Santos Sara Duarte-Silva Luísa Pinto António José Salgado
author_facet	Bárbara Mendes-Pinheiro Carina Soares-Cunha Ana Marote Eduardo Loureiro-Campos Jonas Campos Sandra Barata-Antunes Daniela Monteiro-Fernandes Diogo Santos Sara Duarte-Silva Luísa Pinto António José Salgado
author_sort	Bárbara Mendes-Pinheiro
title	Unilateral Intrastriatal 6-Hydroxydopamine Lesion in Mice: A Closer Look into Non-Motor Phenotype and Glial Response
title_short	Unilateral Intrastriatal 6-Hydroxydopamine Lesion in Mice: A Closer Look into Non-Motor Phenotype and Glial Response
title_full	Unilateral Intrastriatal 6-Hydroxydopamine Lesion in Mice: A Closer Look into Non-Motor Phenotype and Glial Response
title_fullStr	Unilateral Intrastriatal 6-Hydroxydopamine Lesion in Mice: A Closer Look into Non-Motor Phenotype and Glial Response
title_full_unstemmed	Unilateral Intrastriatal 6-Hydroxydopamine Lesion in Mice: A Closer Look into Non-Motor Phenotype and Glial Response
title_sort	unilateral intrastriatal 6-hydroxydopamine lesion in mice: a closer look into non-motor phenotype and glial response
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/5b7bfaea66c64604aa2a882f0e19aabe
work_keys_str_mv	AT barbaramendespinheiro unilateralintrastriatal6hydroxydopaminelesioninmiceacloserlookintononmotorphenotypeandglialresponse AT carinasoarescunha unilateralintrastriatal6hydroxydopaminelesioninmiceacloserlookintononmotorphenotypeandglialresponse AT anamarote unilateralintrastriatal6hydroxydopaminelesioninmiceacloserlookintononmotorphenotypeandglialresponse AT eduardoloureirocampos unilateralintrastriatal6hydroxydopaminelesioninmiceacloserlookintononmotorphenotypeandglialresponse AT jonascampos unilateralintrastriatal6hydroxydopaminelesioninmiceacloserlookintononmotorphenotypeandglialresponse AT sandrabarataantunes unilateralintrastriatal6hydroxydopaminelesioninmiceacloserlookintononmotorphenotypeandglialresponse AT danielamonteirofernandes unilateralintrastriatal6hydroxydopaminelesioninmiceacloserlookintononmotorphenotypeandglialresponse AT diogosantos unilateralintrastriatal6hydroxydopaminelesioninmiceacloserlookintononmotorphenotypeandglialresponse AT saraduartesilva unilateralintrastriatal6hydroxydopaminelesioninmiceacloserlookintononmotorphenotypeandglialresponse AT luisapinto unilateralintrastriatal6hydroxydopaminelesioninmiceacloserlookintononmotorphenotypeandglialresponse AT antoniojosesalgado unilateralintrastriatal6hydroxydopaminelesioninmiceacloserlookintononmotorphenotypeandglialresponse
_version_	1718432178039160832

Unilateral Intrastriatal 6-Hydroxydopamine Lesion in Mice: A Closer Look into Non-Motor Phenotype and Glial Response

Ejemplares similares