NGF stimulation alters the transcriptome and surface TrkB expression in axons of dorsal root ganglion neurons.

Abstract

Nerve growth factor (NGF) is released after injury from macrophages and other cell types and induces an inflammatory response in neurons, characterized by local subcellular reactions and transcriptomic modulation. NGF-induced axonal transcriptome modulation may be crucial for pain initiation and maintenance. To explore these acute modulations, we cultured dorsal root ganglion neurons in microfluidic chambers and stimulated the axons with NGF. We found that axonal levels of the Il7 transcript encoding interleukin-7 (IL-7) are increased after NGF stimulation, followed by IL-7 release from axons. In growth cones of sensory neurons, we also observed a reorganization of the ribosomal subunits 60S and 40S in response to NGF stimulation. In addition, a dynamic change in the spatio-temporal distribution of the Tropomyosin Kinase B (TrkB) receptor occurs at the plasma membrane of sensory neuron growth cones. TrkB is recruited from the endoplasmic reticulum (ER) leading to increased cell surface levels. De-novo synthesis of TrkB seems to be limited to somatic regions of sensory neurons. Thus, cytosolic mechanisms within distal regions of the sensory neurons may autonomously regulate signaling and translation in response to external NGF stimuli.