Abstract
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.
Funder
Ministry for Innovation and Technology in Hungary
nemzeti kutatási, fejlesztési és innovaciós alap
nemzeti kutatási és technológiai hivatal
általános orvostudományi kar, pécsi tudományegyetem
new national excellence program of the ministry for innovation and technology from the source of the national research, development and innovation fund
magyar tudományos akadémia
University of Pécs
Publisher
Springer Science and Business Media LLC
Subject
Cellular and Molecular Neuroscience,Neurology,Immunology,General Neuroscience
Cited by
13 articles.
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