Neurotrophins and cytokines in neuronal plasticity.
Nerve growth factor (NGF) binds to TrkA receptors (neurotrophic) and P75(NTR) (apoptosis or other pathways depending on the coupled adaptor proteins). Brain derived growth factor (BDNF) can bind to TrkB (neurotrophic) and P75(NTR) 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. Inflammatory cytokines are produced in sickness behaviour mimicking depression. Interleukin (IL)1beta 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 IL1beta induces long term depression (LTD) or blocks LTP. The interactions with neurotrophins are complex and frequently reciprocal. However, NGF also contributes to inflammatory 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.
Spedding
Michael
M
Experimental Sciences, Institute of Research Servier, 11 Rue des Moulineaux, 92150 Suresnes, France.
Gressens
Pierre
P
D000818:Animals; D001921:Brain / Q000502:physiology* / Q000503:physiopathology; D019208:Brain-Derived Neurotrophic Factor / Q000502:physiology; D016207:Cytokines / Q000502:physiology*; D004734:Energy Metabolism; D006801:Humans; D008954:Models, Biological; D009414:Nerve Growth Factors / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D010146:Pain / Q000503:physiopathology; D013569:Synapses / Q000502:physiology
D019208:Brain-Derived Neurotrophic Factor; D016207:Cytokines; D009414:Nerve Growth Factors