Final Activity Report Summary - AMOR2HUMAN (Autonomous Mobile Robotics Applied to Human Augmentation)
The overall objective of the proposal was to increase our understanding on how to reproduce in the mature brain the natural repair that follows injury to the immature nervous system and therefore improve recovery from brain injury. This project used our well established model of nervous system injury, namely the rat olivocerebellar path, to investigate the mechanisms by which one growth factor, called BDNF, recreated spontaneous developmental olivary climbing fibre axon re-innervation onto mature cerebellar Purkinje cells.
During the project, we identified three factors that regulated gene expression, i.e. transcription factors, and two groups of molecules that controlled cell-cell interactions, i.e. extracellular matrix molecules, whose expression changed during both spontaneous and BDNF-induced olivocerebellar re-innervation. In order to facilitate this investigation we optimised a simple model of olivocerebellar re-innervation grown in culture. The importance of this technical advance was that it allowed us to examine separately the relative contribution of the newly growing connections versus the target Purkinje cells on the success or failure of neural circuit repair.
We also began testing the role of the two groups of extracellular molecules in BDNF-induced olivocerebellar re-innervation. Although we examined one in the host laboratory, we used transgenic mice which did not express these molecules, namely a group of growth-inhibitory molecules called ephrins, in order to study the second. In addition to providing a means of testing the role of these molecules in post-injury repair, obtaining these mice established a beneficial ongoing international collaboration and increased awareness of European research in Australia.
During the project, we identified three factors that regulated gene expression, i.e. transcription factors, and two groups of molecules that controlled cell-cell interactions, i.e. extracellular matrix molecules, whose expression changed during both spontaneous and BDNF-induced olivocerebellar re-innervation. In order to facilitate this investigation we optimised a simple model of olivocerebellar re-innervation grown in culture. The importance of this technical advance was that it allowed us to examine separately the relative contribution of the newly growing connections versus the target Purkinje cells on the success or failure of neural circuit repair.
We also began testing the role of the two groups of extracellular molecules in BDNF-induced olivocerebellar re-innervation. Although we examined one in the host laboratory, we used transgenic mice which did not express these molecules, namely a group of growth-inhibitory molecules called ephrins, in order to study the second. In addition to providing a means of testing the role of these molecules in post-injury repair, obtaining these mice established a beneficial ongoing international collaboration and increased awareness of European research in Australia.