In vivo Models of α-Synuclein Aggregate Induced Parkinson´s Disease
So far, commercial models of Parkinson’s disease are based on toxin-induced (e.g. MPTP, rotenone) degeneration of dopaminergic neurons, inducing physiological and functional changes similar to Parkinson’s disease. However, even in genetic background without endogenous α-synuclein expression.
SynAging's in vivo PD model presented below is aimed to resemble the natural sporadic onset of the disease by using misfolded α-synuclein aggregates that have recently been accepted in the scientific community as key factors in the etiology of Parkinson’s disease.
WT 15 weeks old C57BL/6 mice are injected once intra-striatal with human α-synuclein oligomers (aSO), or sonicated human α-synuclein fibrils (aSF) at day 0. Cognitive deficits are observed in the Novel Object Recognition (NOR) assay and Spatial Recognition Test (SRT), but not in the Y-maze.
The 'Discrimination Index' given below describes the preference of mice for a novel object / novel environment, which is absent in cognitively impared mice.
SynAging's results further show that mice injected with aSF develop an α-synuclein pathology (seeding and spreading) within
15 days and expanding up to three month. No correlation of α-synuclein pathology and NOR deficits seems to exist.
On the other hand, our results clearly show that mice injected with aSO (single intra-striatal injection) do not develop α-synuclein pathology, even after 3 months. SynAging established that NOR deficits in these mice are correlated with decrease of synaptic markers in the hippocampus by ELISA quantification of synaptophysin, PSD95 and SNAP25, at the same time neuroinflammatory markers are upregulated and microglia are activated.
SynAging has established that mice injected with αSO and challenged with amphetamine displayed an anticlockwise circling behavior, typical for dopaminergic neuron deficit and relevant for Parkinson’s disease. No significant movement degeneration was observed by Rotarod, grip test, string tests and adhesive removal test up to 3 months.
SynAging is investigating this novel PD model further.
SynAging is offering drug candidate trials in the well validated aSO or aSFO induced model!
Please contact us to discuss your interests and requirements for this model.
Product Sheet “In vivo PD Screen”, Download PDF, 1,5 MB