Neurotrophins and Cytokines in Neuronal Plasticity

Nerve growth factor (NGF) binds to TrkA receptors (neurotrophic) and P75NTR (apoptosis or other pathways depending on the coupled adaptor proteins). Brain derived growth factor (BDNF) can bind to TrkB (neurotrophic) and P75NTR receptors. BDNF is the main, activity-dependent, neurotrophin and sculpts neuronal organisation dependent on activity, thereby coupling and balancing effects on excitatory (glutamate) and inhibitory (GABA) transmission—in a synapse-specific manner. Some drugs can interact in a specific way. Positive modulators of AMPA receptors induce BDNF and favour long term potentiation (LTP) and memory processes. Some antidepressants such as tianeptine reverse stress-induced inhibition of LTP and restore neuronal plasticity in brain areas at risk. Infl ammatory cytokines are produced in sickness behaviour mimicking depression. Interleukin (IL)1β can exacerbate the immediate effects of stressors, and enhance and prolong the overall effects, which may be protective in preventing overuse or by increasing conservation-withdrawal: in some synapses IL1β induces long term depression (LTD) or blocks LTP. The interactions with neurotrophins are complex and frequently reciprocal. However, NGF also contributes to infl ammatory situations and mediates pain responses. This interplay is poorly understood but may be critical in cerebral palsy, neurodegenerative disorders such as amyotrophic lateral sclerosis and multiple sclerosis, and even Alzheimer's disease.