Raised plasma nerve growth factor levels associated with early-stage romantic love.
NATURE REVIEWS | NEUROSCIENCE VOLUME 4 | APRIL 2003 | 299 The era of growth factor research began fifty years ago with the discovery of nerve growth factor (NGF). Since then, the momentum to study the NGF — or neurotrophin — family has never abated because of their continuous capacity to provide new insights into neural function; the influence of neurotrophins spans from developmental neurobiology to neurodegenerative and psychiatric disorders. In addition to their classic effects on neuronal cell survival, neurotrophins can also regulate axonal and dendritic growth and guidance, synaptic structure and connections, neurotransmitter release, LONG-TERM POTENTIATION (LTP) and synaptic plasticity. The surprising discovery that neurotrophins and their receptors do not exist in Drosophila melanogaster or Caenorhabditis elegans reinforced the idea that these proteins are not absolutely necessary for the development of neuronal circuits per se, but are involved in ‘higher-order’ activities. For example, neurotrophins and their receptors influence many aspects of neuronal activity that result in the generation of new synaptic connections, which can be long lasting. Alterations in neurotrophin levels have profound effects on a wide variety of phenomena, including myelination, regeneration, pain, aggression, depression and substance abuse. The actions of neurotrophins depend on two different transmembrane-receptor signalling systems — the Trk receptor tyrosine kinases and the p75 neurotrophin receptor. Despite considerable progress in understanding the roles of these receptors, additional mechanisms are needed to explain the many cellular and synaptic interactions that occur between neurons. An emerging view is that neurotrophin receptors act as sensors for various extracellular and intracellular inputs, and several new mechanisms have recently been put forward. Here, I will consider several ways in which Trk and p75 receptors might account for the unique effects of neurotrophins on behaviour and higher-order activities.