Session Information
Date: Tuesday, June 21, 2016
Session Title: Parkinson's disease: Pathophysiology
Session Time: 12:30pm-2:00pm
Location: Exhibit Hall located in Hall B, Level 2
Objective: To determine the contribution of the adaptive immune system in the pathogenesis of a mouse model of Parkinson’s disease (PD) based on AAV1/2 driven expression of human A53T α-synuclein (aSyn).
Background: An aspect of PD pathogenesis which has not yet been well characterized is the role of inflammation in the disease progression. Although some changes in the immune response of PD patients have been described, it is not certain whether these alterations are pathogenetically relevant. Data from animal models of PD are controversial with reports of a detrimental effect of T-cells in the MPTP mouse model and a protective role in the 6-OHDA model. We aim to analyze the impact of the adaptive immune system in a new PD model of AAV1/2 mediated overexpression of human A53T aSyn since this model better reflects clinical and paraclinical aspects of the human disease.
Methods: AAV1/2 A53T aSyn or AAV1/2 empty vector (EV) at a concentration of 5.1 x 10exp12 gp/ml were unilaterally injected into the right substantia nigra (SN) of male adult C57BL/6 or RAG-1-/- mice. Clinical examination in both groups was performed by rotarod analysis 4 and 8 weeks after AAV injection. Paw use asymmetry was examined by cylinder test at weeks 5 and 9 after injection. Immunohistochemistry was used to analyze lymphocyte infiltration into the SN. FACS analysis was implemented to investigate brain infiltrates.
Results: Significant impairment of rotarod performance was observed in the wt A53T aSyn injected group compared to the RAG-1-/- A53T aSyn mice at both 4 and 8 weeks after AAV injection (p<0.01; p<0.001). Significant paw use asymmetry was seen in the wt A53T aSyn injected group with preference of the right front paw when compared to RAG-1-/- A53T aSyn group 5 and 9 weeks post injection (p<0.001; p<0.05). Immunohistochemical staining revealed an increase of CD8>CD4 T-cell numbers in wt A53T aSyn SN, while EV injected wt mice displayed T-cell numbers comparable to untreated wt mice. FACS analysis using CD69 activation marker showed a high activation of CD8+ and CD4+ T-cells (76%; 62%) in the brain after A53T aSyn injection.
Conclusions: These data suggest a detrimental effect of lymphocytes in this AAV1/2 A53T aSyn mouse model of PD.
To cite this abstract in AMA style:
A.A. Karikari, M. Gehmeyr, E. Ribechini, V. Maltese, J. Volkmann, J.M. Brotchie, J.B. Koprich, M.B. Lutz, C.W. Ip. Lymphocytes have a detrimental effect on motor behavior in the AAV1/2 A53T α-synuclein mouse model of Parkinson’s disease [abstract]. Mov Disord. 2016; 31 (suppl 2). https://www.mdsabstracts.org/abstract/lymphocytes-have-a-detrimental-effect-on-motor-behavior-in-the-aav12-a53t-synuclein-mouse-model-of-parkinsons-disease/. Accessed November 21, 2024.« Back to 2016 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/lymphocytes-have-a-detrimental-effect-on-motor-behavior-in-the-aav12-a53t-synuclein-mouse-model-of-parkinsons-disease/