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

Abstract

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