Thea Pinholt Lillethorup

PARKINSON’S DISEASE MODELS OF ABNORMAL PROTEIN AGGREGATION IN THE GOTTINGEN MINIPIG CNS: Brain Prize Meeting 2015

Research output: Contribution to conferencePosterResearchpeer-review

Background:
Parkinson's disease (PD) animal models are important translational steps toward clinical applications. The Göttingen minipig(GM) has a large gyrencephalic brain (6x5x4cm) that can be examined using conventional scanning modalities. Preclinical neuromodulatory devices can be evaluated in GM models. aSYN is a known pathological protein in PD. Aggregation or overexpression occurs in human PD and has been used to induce PD in other animal models.

Aim:
We aim to develop and validate novel models of PD in the GM based on abnormal protein aggregation.

Methods:
Using human intended MRI-guided stereotaxic neurosurgery, we are inducing a PD-syndrome in GM via overexpression of mutated human aSYN using viral vectors or intracerebroventricular administration of an ubiquitin proteasome system inhibitor.
The resulting pathological changes are quantified by neurological tests, PET-imaging of monaminergic function and neuroinflammation, HPLC and post mortem histological evaluation for aSYN and neuroinflammatory markers.

Results:
Data from ongoing studies with the different models demonstrate gait disturbances, bradykinesia, deficits in monoaminergic neurotransmission, alterations in the aSYN levels in CNS and histological signs of PD including aSYN accumulation.

Discussion:
We predict that these animal models will be beneficial in the understanding of pathological mechanisms of human PD and in the testing of novel therapeutic strategies.
Original languageDanish
Publication year3 Nov 2015
Publication statusPublished - 3 Nov 2015

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