WP7: Magnetic manipulation of cellular signalling in organotypic brain slices and in vivo models of Parkinson’s disease

Parkinson’s Disease is characterised by the loss of dopaminergic neurons in the brain. Current strategies of treating Parkinson’s Disease include transplantation of dopaminergic neurons into the brain. However, one of the major challenges in the transplantation field is the ability to control the outgrowth and integration of dopaminergic cells in their target area of the brain.

In this work package, we have developed a model of Parkinson’s Disease using rat brain slices grown in a dish. The brain is cut into slices using a fast vibrating blade and these brain slices are then placed on special membranes that allow access to nutrients from specially formulated media below the slice and oxygen from above. These slices remain healthy for several weeks but show degeneration of dopaminergic neurons, the principal hallmark of Parkinson’s Disease.

The aims of WP7 are to be able to control the differentiation and outgrowth of transplanted cells in slices using MNPs and magnetic fields. The slice model enables us to apply the magnetic nanoparticle (MNP) “temp” mode and “space” mode strategies developed in single cells to a model system that retains the structures and connections of the brain, thus mimicking the whole brain more closely. This will provide for a more informed translation to in vivo models of Parkinson’s Disease that seek to improve the efficacy of cell transplantation therapy in Parkinson’s Disease.