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Olfactory Bulb Excitotoxicity as a Gap-Filling Mechanism Underlying the Link Between Traumatic Brain Injury-Induced Secondary Neuronal Degeneration and Parkinson’s Disease-Like Pathology

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Abstract

There is increasing preclinical and clinical data supporting a potential association between Traumatic Brain Injury (TBI) and Parkinson’s disease (PD). It has been suggested that the glutamate-induced excitotoxicity underlying TBI secondary neuronal degeneration (SND) might be associated with further development of PD. Interestingly, an accumulation of extracellular glutamate and olfactory dysfunction are both sharing pathological conditions in TBI and PD. The possible involvement of glutamate excitotoxicity in olfactory dysfunction has been recently described, however, the role of olfactory bulbs (OB) glutamate excitotoxicity as a possible mechanism involved in the association between TBI and PD-related neurodegeneration has not been investigated yet. We examined the number of nigral dopaminergic neurons (TH +), nigral α-synuclein expression, the striatal dopamine transporter (DAT) expression, and motor performance after bilateral OB N-Methyl-D-Aspartate (NMDA)-induced excitotoxic lesions in rodents. Bulbar NMDA administration induced a decrease in the number of correct choices in the discrimination tests one week after lesions (p < 0.01) and a significant decrease in the number of nigral DAergic neurons (p < 0.01) associated with an increase in α-synuclein expression (p < 0.01). No significant striatal changes in DAT expression or motor alterations were observed. Our results show an association between TBI-induced SND and PD-related neurodegeneration suggesting that the OB excitotoxicity occurring in TBI SND may be a filling gap mechanism underlying the link between TBI and PD-like pathology.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Funding

This work was partially supported by a research grant (110610) from Fundació La Marató TV3 and a grant from the Spanish Ministerio de Ciencia, Innovación y Universidades (PI19/00806).

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Authors and Affiliations

  1. INGENIO, IRCE, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), IDIBAPS-CELLEX, Department 2B, Rosselló 149-153, 08036, Barcelona, Catalonia, Spain

    Concepció Marin, Mireya Fuentes, Isam Alobid, Valeria Tubita, María Jesús Rojas-Lechuga & Joaquim Mullol

  2. Centre for Biomedical Investigation in Respiratory Diseases (CIBERES), Barcelona, Spain

    Concepció Marin, Mireya Fuentes, Isam Alobid, María Jesús Rojas-Lechuga & Joaquim Mullol

  3. Rhinology Unit and Smell Clinic, ENT Department, Hospital Clinic, Villarroel 170, 08036, Barcelona, Catalonia, Spain

    Isam Alobid, María Jesús Rojas-Lechuga & Joaquim Mullol

  4. Universitat de Barcelona, Barcelona, Catalonia, Spain

    Valeria Tubita

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  1. Concepció Marin
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Contributions

CM designed the project, performed the behavioral experiments, supervised the experiments, analyzed the data and wrote the manuscript; MF performed the laboratory experiments and technical assistance; IA, VT, MJR-L. performed partial data analysis and revised the manuscript; JM designed the project, supervised the experiments, performed partial data analysis, and revised the manuscript.

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Correspondence to Concepció Marin or Joaquim Mullol.

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All experiments were carried out following the European (2010/63/UE) and Spanish (RD 53/2013) regulation for the care and use of laboratory animals and approved by the local Government (Generalitat de Catalunya, #372/17, #373/17). The Ethics Committee from the Hospital Clinic de Barcelona approved this study.

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Marin, C., Fuentes, M., Alobid, I. et al. Olfactory Bulb Excitotoxicity as a Gap-Filling Mechanism Underlying the Link Between Traumatic Brain Injury-Induced Secondary Neuronal Degeneration and Parkinson’s Disease-Like Pathology. Neurochem Res 47, 1025–1036 (2022). https://doi.org/10.1007/s11064-021-03503-x

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