ABSTRACT

In the past two decades there has been a rapid increase in our knowledge of growth factors and their function in the central nervous system (CNS) during normal and diseased situations. Many initial studies utilised direct application of purified growth factors to cell culture systems in vitro and central administration in vivo to suggest that growth factors may have beneficial actions in CNS disorders. As our understanding of growth factors, their receptors and signalling pathways, has expanded it has become clear that there are a large number of these growth factors and that it may be possible to modulate their expression by the use of small molecules. This review will focus on the role of brain-derived neurotrophic factor (BDNF) and its receptor, TrkB in psychiatric and neurological disorders. There is now considerable evidence that BDNF can protect neurones in culture and that central infusion or delivery of BDNF with adenoviral or lenti viral vectors can provide neuroprotection in animal models of Parkinson`s disease, stroke and head trauma. However, there is also a growing body of evidence indicating that BDNF is also a central player in depression and other psychiatric disorders. Several physical (electroconvulsive shock, stress) and pharmacological interventions (selective serotonin reuptake inhibitors or SSRI’s, AMPAkines, nicotine) have been shown to increase BDNF expression. Many of these small molecules can penetrate the brain easily and may provide a means of modulating BDNF expression and hence may be useful as therapies for the treatment of CNS disorders. This review will discuss the effects of BDNF in Parkinson’s disease, stroke, epilepsy and depression and discuss cAMP and non-cAMP dependent methods of modulating BDNF in the CNS with a focus on treating depression.