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Article

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

by
Bárbara Mendes-Pinheiro
1,2,
Carina Soares-Cunha
1,2,
Ana Marote
1,2,
Eduardo Loureiro-Campos
1,2,
Jonas Campos
1,2,
Sandra Barata-Antunes
1,2,
Daniela Monteiro-Fernandes
1,2,
Diogo Santos
1,2,
Sara Duarte-Silva
1,2,
Luísa Pinto
1,2 and
António José Salgado
1,2,*
1
Life and Health Sciences Research Institute (ICVS), School of Medicine, Campus de Gualtar, University of Minho, 4710-057 Braga, Portugal
2
ICVS/3B’s—PT Government Associate Laboratory, 4805-017 Guimarães, Portugal
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2021, 22(21), 11530; https://doi.org/10.3390/ijms222111530
Submission received: 23 September 2021 / Revised: 14 October 2021 / Accepted: 19 October 2021 / Published: 26 October 2021
(This article belongs to the Special Issue Dissecting Neurological and Neuropsychiatric Diseases: Neurodegeneration and Neuroprotection)
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Abstract

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.
Keywords: Parkinson’s disease; 6-OHDA; unilateral; striatum; dopaminergic degeneration; motor behavior; non-motor behavior; glial response Parkinson’s disease; 6-OHDA; unilateral; striatum; dopaminergic degeneration; motor behavior; non-motor behavior; glial response

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MDPI and ACS Style

Mendes-Pinheiro, B.; Soares-Cunha, C.; Marote, A.; Loureiro-Campos, E.; Campos, J.; Barata-Antunes, S.; Monteiro-Fernandes, D.; Santos, D.; Duarte-Silva, S.; Pinto, L.; et al. Unilateral Intrastriatal 6-Hydroxydopamine Lesion in Mice: A Closer Look into Non-Motor Phenotype and Glial Response. Int. J. Mol. Sci. 2021, 22, 11530. https://doi.org/10.3390/ijms222111530

AMA Style

Mendes-Pinheiro B, Soares-Cunha C, Marote A, Loureiro-Campos E, Campos J, Barata-Antunes S, Monteiro-Fernandes D, Santos D, Duarte-Silva S, Pinto L, et al. Unilateral Intrastriatal 6-Hydroxydopamine Lesion in Mice: A Closer Look into Non-Motor Phenotype and Glial Response. International Journal of Molecular Sciences. 2021; 22(21):11530. https://doi.org/10.3390/ijms222111530

Chicago/Turabian Style

Mendes-Pinheiro, Bárbara, Carina Soares-Cunha, Ana Marote, Eduardo Loureiro-Campos, Jonas Campos, Sandra Barata-Antunes, Daniela Monteiro-Fernandes, Diogo Santos, Sara Duarte-Silva, Luísa Pinto, and et al. 2021. "Unilateral Intrastriatal 6-Hydroxydopamine Lesion in Mice: A Closer Look into Non-Motor Phenotype and Glial Response" International Journal of Molecular Sciences 22, no. 21: 11530. https://doi.org/10.3390/ijms222111530

APA Style

Mendes-Pinheiro, B., Soares-Cunha, C., Marote, A., Loureiro-Campos, E., Campos, J., Barata-Antunes, S., Monteiro-Fernandes, D., Santos, D., Duarte-Silva, S., Pinto, L., & José Salgado, A. (2021). Unilateral Intrastriatal 6-Hydroxydopamine Lesion in Mice: A Closer Look into Non-Motor Phenotype and Glial Response. International Journal of Molecular Sciences, 22(21), 11530. https://doi.org/10.3390/ijms222111530

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