Characterisation of embryonic ventral mesencephalon grafts in a rat model of Parkinson’s disease
mesheuropmc: nervous system
The work discussed in this thesis adds further knowledge regarding the survival of embryonic dopaminergic grafts, derived from the rat ventral mesencephalon, in the rat model of Parkinson’s disease, in terms of the populations of cells involved, their distribution within the grafts, and how these are affected by the donor age and the host environment in to which they are implanted.\ud The current data further reinforce the notion that harvesting ventral mesencephalic tissue at embryonic day 12 (E12) before the peak of dopamine neurogenesis yields more dopamine cells in the grafts and, more importantly, also yields more nigral A9 type dopamine neurons, which are an important determinant for functional recovery.\ud Following on from this, commitment of dopamine neural precursor cells to the two dopamine neuron phenotypes, and how this is affected by the host environment was investigated, by grafting rat E12 and E14 ventral mesencephalon tissue into different cerebral targets. Brain regions were chosen that receive either the nigral A9 type dopamine, ventral tegmental A10 type dopamine or noradrenaline innervation. The yield of A9 type dopamine neurons was found to be influenced both by the environment within the graft and by the host environment in the transplantation site to a higher extent than the yield of A10 type dopamine neurons. \ud Dopaminergic progenitors procured from rat embryos at E12 were shown to have a greater potential to proliferate post-grafting and differentiate into mature dopamine neurons as compared to embryos at E14. In vivo proliferation of younger precursor cells significantly contributed to the higher yields of the A9 type dopamine neurons in the grafts. If this improved yield of the A9 type dopamine neurons could be reproduced in human trials, fewer human donors might suffice to produce functional grafts in Parkinson’s disease patients.