Tales of Neurotrophism

: Neurotrophic Factors in Neural Stem Cells and the 6-OHDA Model of Parkinson's Disease

Abstract

This thesis is divided in three independent result chapters or tales of neurotrophism. On each of these chapters I sought to characterize or validate novel neurotrophic factors and their ability to promote neuronal differentiation or survival. In the first chapter, I will establish the role of clusterin as an astrocyte-secreted protein that acts as a novel neurotrophic factor for human neural stem cells in vitro and I will discuss its implications for neurodegeneration in Alzheimer’s disease. The second chapter is focused on galanin – a pleiotropic neuropeptide with neuroprotective and neuroregenerative properties in the nervous system. I will study the effects of galanin on neural differentiation of fetal and adult mouse neural stem cells in vitro and the consequences of galanin disruption on adult neurogenesis in vivo. I will consider my findings in relation to the complex behavioural phenotypes described for galanin knockout mice. In the final chapter, I will test the efficacy of lentiviral delivery of CDNF (Conserved Dopamine Neurotrophic Factor) and MANF (Mesencephalic Astrocyte-derived Neurotrophic Factor) – members of a newly-described family of neurotrophic factors for dopaminergic neurons – in the 6-hydroxy-dopamine rat model of Parkinson’s disease and I will discuss our findings in the context of gene therapy
approaches for this disease.

Date of Award	14 May 2013
Original language	English
Awarding Institution	University of Bristol
Supervisor	Maeve A Caldwell (Supervisor) & David Wynick (Supervisor)