Neurodegeneration in the centrally-projecting Edinger–Westphal nucleus contributes to the non-motor symptoms of Parkinson’s disease in the rat
Abstract Background The neuropathological background of major depression and anxiety as non-motor symptoms of Parkinson’s disease is much less understood than classical motor symptoms. Although, neurodegeneration of the Edinger–Westphal nucleus in human Parkinson’s disease is a known phenomenon, its...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-02-01
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| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12974-022-02399-w |
| _version_ | 1818486351584034816 |
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| author | Balázs Ujvári Bence Pytel Zsombor Márton Máté Bognár László Ákos Kovács József Farkas Tamás Gaszner Gergely Berta Angéla Kecskés Viktória Kormos Boglárka Farkas Nóra Füredi Balázs Gaszner |
| author_facet | Balázs Ujvári Bence Pytel Zsombor Márton Máté Bognár László Ákos Kovács József Farkas Tamás Gaszner Gergely Berta Angéla Kecskés Viktória Kormos Boglárka Farkas Nóra Füredi Balázs Gaszner |
| author_sort | Balázs Ujvári |
| collection | DOAJ |
| description | Abstract Background The neuropathological background of major depression and anxiety as non-motor symptoms of Parkinson’s disease is much less understood than classical motor symptoms. Although, neurodegeneration of the Edinger–Westphal nucleus in human Parkinson’s disease is a known phenomenon, its possible significance in mood status has never been elucidated. In this work we aimed at investigating whether neuron loss and alpha-synuclein accumulation in the urocortin 1 containing (UCN1) cells of the centrally-projecting Edinger–Westphal (EWcp) nucleus is associated with anxiety and depression-like state in the rat. Methods Systemic chronic rotenone administration as well as targeted leptin–saporin-induced lesions of EWcp/UCN1 neurons were conducted. Rotarod, open field and sucrose preference tests were performed to assess motor performance and mood status. Multiple immunofluorescence combined with RNAscope were used to reveal the functional–morphological changes. Two-sample Student’s t test, Spearman’s rank correlation analysis and Mann–Whitney U tests were used for statistics. Results In the rotenone model, besides motor deficit, an anxious and depression-like phenotype was detected. Well-comparable neuron loss, cytoplasmic alpha-synuclein accumulation as well as astro- and microglial activation were observed both in the substantia nigra pars compacta and EWcp. Occasionally, UCN1-immunoreactive neuronal debris was observed in phagocytotic microglia. UCN1 peptide content of viable EWcp cells correlated with dopaminergic substantia nigra cell count. Importantly, other mood status-related dopaminergic (ventral tegmental area), serotonergic (dorsal and median raphe) and noradrenergic (locus ceruleus and A5 area) brainstem centers did not show remarkable morphological changes. Targeted partial selective EWcp/UCN1 neuron ablation induced similar mood status without motor symptoms. Conclusions Our findings collectively suggest that neurodegeneration of urocortinergic EWcp contributes to the mood-related non-motor symptoms in toxic models of Parkinson’s disease in the rat. |
| first_indexed | 2024-12-10T16:21:47Z |
| format | Article |
| id | doaj.art-749adc7e269846f8b223552ae1b54b24 |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-12-10T16:21:47Z |
| publishDate | 2022-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-749adc7e269846f8b223552ae1b54b242022-12-22T01:41:47ZengBMCJournal of Neuroinflammation1742-20942022-02-0119111710.1186/s12974-022-02399-wNeurodegeneration in the centrally-projecting Edinger–Westphal nucleus contributes to the non-motor symptoms of Parkinson’s disease in the ratBalázs Ujvári0Bence Pytel1Zsombor Márton2Máté Bognár3László Ákos Kovács4József Farkas5Tamás Gaszner6Gergely Berta7Angéla Kecskés8Viktória Kormos9Boglárka Farkas10Nóra Füredi11Balázs Gaszner12Department of Anatomy, Research Group for Mood Disorders, Medical School, University of PécsDepartment of Anatomy, Research Group for Mood Disorders, Medical School, University of PécsDepartment of Anatomy, Research Group for Mood Disorders, Medical School, University of PécsDepartment of Anatomy, Research Group for Mood Disorders, Medical School, University of PécsDepartment of Anatomy, Research Group for Mood Disorders, Medical School, University of PécsDepartment of Anatomy, Research Group for Mood Disorders, Medical School, University of PécsDepartment of Anatomy, Research Group for Mood Disorders, Medical School, University of PécsDepartment of Medical Biology, Medical School, University of PécsDepartment of Pharmacology and Pharmacotherapy, Medical School & Szentágothai Research Centre, Molecular Pharmacology Research Group, University of PécsDepartment of Pharmacology and Pharmacotherapy, Medical School & Szentágothai Research Centre, Molecular Pharmacology Research Group, University of PécsDepartment of Anatomy, Research Group for Mood Disorders, Medical School, University of PécsDepartment of Anatomy, Research Group for Mood Disorders, Medical School, University of PécsDepartment of Anatomy, Research Group for Mood Disorders, Medical School, University of PécsAbstract Background The neuropathological background of major depression and anxiety as non-motor symptoms of Parkinson’s disease is much less understood than classical motor symptoms. Although, neurodegeneration of the Edinger–Westphal nucleus in human Parkinson’s disease is a known phenomenon, its possible significance in mood status has never been elucidated. In this work we aimed at investigating whether neuron loss and alpha-synuclein accumulation in the urocortin 1 containing (UCN1) cells of the centrally-projecting Edinger–Westphal (EWcp) nucleus is associated with anxiety and depression-like state in the rat. Methods Systemic chronic rotenone administration as well as targeted leptin–saporin-induced lesions of EWcp/UCN1 neurons were conducted. Rotarod, open field and sucrose preference tests were performed to assess motor performance and mood status. Multiple immunofluorescence combined with RNAscope were used to reveal the functional–morphological changes. Two-sample Student’s t test, Spearman’s rank correlation analysis and Mann–Whitney U tests were used for statistics. Results In the rotenone model, besides motor deficit, an anxious and depression-like phenotype was detected. Well-comparable neuron loss, cytoplasmic alpha-synuclein accumulation as well as astro- and microglial activation were observed both in the substantia nigra pars compacta and EWcp. Occasionally, UCN1-immunoreactive neuronal debris was observed in phagocytotic microglia. UCN1 peptide content of viable EWcp cells correlated with dopaminergic substantia nigra cell count. Importantly, other mood status-related dopaminergic (ventral tegmental area), serotonergic (dorsal and median raphe) and noradrenergic (locus ceruleus and A5 area) brainstem centers did not show remarkable morphological changes. Targeted partial selective EWcp/UCN1 neuron ablation induced similar mood status without motor symptoms. Conclusions Our findings collectively suggest that neurodegeneration of urocortinergic EWcp contributes to the mood-related non-motor symptoms in toxic models of Parkinson’s disease in the rat.https://doi.org/10.1186/s12974-022-02399-wRotenoneSaporinUrocortin 1DepressionAnxietyRat |
| spellingShingle | Balázs Ujvári Bence Pytel Zsombor Márton Máté Bognár László Ákos Kovács József Farkas Tamás Gaszner Gergely Berta Angéla Kecskés Viktória Kormos Boglárka Farkas Nóra Füredi Balázs Gaszner Neurodegeneration in the centrally-projecting Edinger–Westphal nucleus contributes to the non-motor symptoms of Parkinson’s disease in the rat Journal of Neuroinflammation Rotenone Saporin Urocortin 1 Depression Anxiety Rat |
| title | Neurodegeneration in the centrally-projecting Edinger–Westphal nucleus contributes to the non-motor symptoms of Parkinson’s disease in the rat |
| title_full | Neurodegeneration in the centrally-projecting Edinger–Westphal nucleus contributes to the non-motor symptoms of Parkinson’s disease in the rat |
| title_fullStr | Neurodegeneration in the centrally-projecting Edinger–Westphal nucleus contributes to the non-motor symptoms of Parkinson’s disease in the rat |
| title_full_unstemmed | Neurodegeneration in the centrally-projecting Edinger–Westphal nucleus contributes to the non-motor symptoms of Parkinson’s disease in the rat |
| title_short | Neurodegeneration in the centrally-projecting Edinger–Westphal nucleus contributes to the non-motor symptoms of Parkinson’s disease in the rat |
| title_sort | neurodegeneration in the centrally projecting edinger westphal nucleus contributes to the non motor symptoms of parkinson s disease in the rat |
| topic | Rotenone Saporin Urocortin 1 Depression Anxiety Rat |
| url | https://doi.org/10.1186/s12974-022-02399-w |
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