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  Modelling Non-motor Symptoms of Parkinson’s Disease: AAV Mediated Overexpression of Alpha-synuclein in Rat Hippocampus and Basal Ganglia [Turk J Neurol]
Turk J Neurol. 2020; 26(4): 322-329 | DOI: 10.4274/tnd.2020.22308  

Modelling Non-motor Symptoms of Parkinson’s Disease: AAV Mediated Overexpression of Alpha-synuclein in Rat Hippocampus and Basal Ganglia

Sevgi Uğur Mutluay1, Elif Çınar1, Gül Yalçın Çakmaklı2, Ayşe Ulusoy3, Bülent Elibol2, Banu Cahide Tel1
1Hacettepe University Faculty of Pharmacy, Department of Pharmacology, Ankara, Turkey
2Hacettepe University Faculty of Medicine, Department of Neurology, Ankara, Turkey
3German Center for Neurodegenerative Diseases (DZNE) Bonn, Germany

Objective: Our aim was to investigate the relation between unilateral hippocampal and/or nigral alpha-synucleinopathy and cognitive dysfunction, anxiety and anhedonia.
Materials and Methods: Female Sprague-Dawley rats were stereotactically injected adeno-associated viruses carrying alpha-synuclein (α-syn) into unilateral dentate gyrus (DG), substantia nigra (SN) or both SN + DG. The animals were tested for motor functions and memory, spatial learning, anxiety and hedony. Levels of α-syn and synaptophysin were evaluated by Western blot (WB) analysis.
Results: In apomorphine-induced rotation test, a mild motor dysfunction was found in SN-α-syn group compared to control. DG- α-syn group showed memory impairment in novel object recognition test. All the α-syn injected groups spent more time to find the platform compared to controls in Morris water maze but this difference did not reach statistical significance. DG-α-syn group consumed more sucrose solution in sucrose consumption test and spent more time on the open arm in elevated plus maze, while the opposite was observed in SN-α-syn group compared to controls. We showed α-syn protein expression in the injected areas of all α-syn groups by WB and immunohistochemical staining. In WB analysis, both hippocampal and striatal synaptophysin expression levels were lower in the α-syn groups compared to controls.
Conclusion: Parkinson’s disease (PD) is characterized by both motor and non-motor symptoms (NMS). However, an animal model recapitulating NMS with the background of dopaminergic denervation is still lacking. This model may help to investigate hippocampal α-syn pathology correlated especially with cognitive dysfunction and other NMS of PD.

Keywords: Parkinson’s disease, adeno-associated viral vector, behavioral tests, hippocampus, substantia nigra


Sevgi Uğur Mutluay, Elif Çınar, Gül Yalçın Çakmaklı, Ayşe Ulusoy, Bülent Elibol, Banu Cahide Tel. Modelling Non-motor Symptoms of Parkinson’s Disease: AAV Mediated Overexpression of Alpha-synuclein in Rat Hippocampus and Basal Ganglia. Turk J Neurol. 2020; 26(4): 322-329

Corresponding Author: Sevgi Uğur Mutluay, Türkiye


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