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

• Published in: Molecular neurobiology 2019-02, Vol.56 (2), p.1082-1095
• Main Authors: Ilkiw, Jessica L., Kmita, Luana C., Targa, Adriano D. S., Noseda, Ana Carolina D., Rodrigues, Lais S., Dorieux, Flávia W. C., Fagotti, Juliane, dos Santos, Patrícia, Lima, Marcelo M. S.
• Format: Article
• Language: English
• Subjects: 6-Hydroxydopamine; Animal models; Animals; Behavior; Behavior, Animal - drug effects; Biomedical and Life Sciences; Biomedicine; Cell Biology; Depression - chemically induced; Disease Models, Animal; Dopamine - metabolism; Dopamine receptors; Dopaminergic Neurons - drug effects; Dopaminergic Neurons - metabolism; Interneurons; Lesions; Male; Mental depression; Movement disorders; Neurobiology; Neurodegenerative diseases; Neurology; Neurosciences; Neurotransmission; Olfaction; Olfaction disorders; Olfactory bulb; Olfactory Bulb - drug effects; Olfactory Bulb - injuries; Olfactory Bulb - pathology; Parkinson Disease - drug therapy; Parkinson Disease - pathology; Parkinson's disease; Rats, Wistar; Substantia nigra; Substantia Nigra - drug effects; Substantia Nigra - pathology
• ISSN: 0893-7648; 1559-1182
• DOI: 10.1007/s12035-018-1134-5

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.