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Dopaminergic Lesion in the Olfactory Bulb Restores Olfaction and Induces Depressive-Like Behaviors in a 6-OHDA Model of Parkinson’s Disease

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Abstract

Olfactory impairments and depressive behavior are commonly reported by individuals with Parkinson’s disease (PD) being observed before motor symptoms. The mechanisms underlying these clinical manifestations are not fully elucidated. However, the imbalance in dopaminergic neurotransmission seems to play an important role in this context. In patients and animal models of PD, an increase in the dopaminergic interneurons of the glomerular layer in olfactory bulb (OB-gl) is observed, which may contribute to the olfactory impairment. In addition, neuronal imbalance in OB is related to depressive symptoms, as demonstrated by chemical olfactory bulbectomy. In view of that, we hypothesized that a reduction in the number or density of dopaminergic neurons present in OB could promote an olfactory improvement and, in contrast, would accentuate the depressive-like behaviors in the 6-hydroxydopamine (6-OHDA) model of PD. Therefore, we performed single or double injections of 6-OHDA within the substantia nigra pars compacta (SNpc) and/or in the OB-gl. We observed that, after 7 days, the group with nigral lesion exhibited olfactory impairment, as well as the group with the lesion in the OB-gl. However, the combination of the lesions prevented the occurrence of hyposmia. In relation to depressive-like behaviors, we observed that the SNpc injury promoted depressive-like behavior, being accentuated after a double injury. Our results demonstrated the importance of the dopaminergic neurons of the OB-gl in different non-motor features of PD, since the selective reduction of these periglomerular neurons was able to induce olfactory impairment and depressive-like behaviors.

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Acknowledgements

The authors wish to express their sincere gratitude to Fabio Roberto Caetano from Physiology Department of UFPR for the technical assistance.

Funding

This paper was supported by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Fundação Araucária (Programa de Apoio a Núcleos de Excelência—PRONEX), and the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) (research grant 431279/2016-0) Brazil. MMSL is recipient of CNPq fellowship (research grant 305986/2016-3).

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  1. Laboratório de Neurofisiologia. Departamento de Fisiologia, Universidade Federal do Paraná, Av. Francisco H. dos Santos s/n,, Curitiba, PR, 81531-990, Brazil

    Jessica L. Ilkiw, Luana C. Kmita, Adriano D. S. Targa, Ana Carolina D. Noseda, Lais S. Rodrigues, Flávia W. C. Dorieux, Juliane Fagotti, Patrícia dos Santos & Marcelo M. S. Lima

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  1. Jessica L. Ilkiw
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Correspondence to Marcelo M. S. Lima.

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All the experiments were carried out in accordance with the guidelines of the Committee for the Care and Use of Laboratory Animals, United States National Institutes of Health. In addition, the protocol complies with the recommendations of Federal University of Paraná and was approved by the institutional ethics committee (approval ID no. 910).

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Ilkiw, J.L., Kmita, L.C., Targa, A.D.S. et al. Dopaminergic Lesion in the Olfactory Bulb Restores Olfaction and Induces Depressive-Like Behaviors in a 6-OHDA Model of Parkinson’s Disease. Mol Neurobiol 56, 1082–1095 (2019). https://doi.org/10.1007/s12035-018-1134-5

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