UROCORTIN1 NEURONS OF THE CENTRALLY PROJECTING EDINGER-WESTPHAL NUCLEUS CONTRIBUTE TO NON-MOTOR SYMPTOMS OF PARKINSON’S DISEASE IN THE RAT
01/29/2020
B.Ujvari1, N.Füredi1, T.Gaszner1, L.A.Kovács1, J.Farkas1, A.Kecskés1, V.Kormos1, A.Hunyady1, B.Gaszner1
Non-motor symptoms of Parkinson’s disease (PD) like depression and anxiety deteriorate the quality of life in a greater extent, than the well-known disabilities in motor control including, rigor, tremor and bradykinesia. The diagnosis of PD is based on cell loss in the dopaminergic substantia nigra (SN) and the presence of Lewy bodies. Morphological changes were found in numerous other nuclei of the brainstem including the Edinger-Westphal nucleus. Its centrally projecting cells (cpEW) expresses urocortin1 (Ucn1) that contributes to stress response and emotional reactions. We hypothesized that besides the well-known neurodegenerative alterations in the SN, morphological changes in the urocortinergic cpEW will occur, that contributes to mood disorders. To induce PD and to show the involvement of cpEW-Ucn1 in PD-associated mood disorders, six weeks subcutaneous rotenone treatment was used as a toxic model. Open field (OFT), sucrose preference (SPT) and rotarod tests were used to assess the mood status and motor performance. Morphological changes were assessed by multiple label immunofluorescence. Rotenone treated rats showed increased anhedonia and anxiety level and they showed motor dysfunction. The model’s validity was proven by the reduced dopaminergic cell count in the SN that correlated with the loss of the urocortinergic cells. Ucn1 immunoreactivity was elevated while the Ucn1 mRNA expression was reduced in cpEW. Activated microglia cells were found performing phagocytosis on Ucn1 cells upon rotenone treatment. The impairment of the Ucn1 neurons in the cpEW may contribute to the non-motor symptoms of PD. Supported by: NKFIH-FK124188