Nerve growth factor alters microtubule targeting agent-induced neurotransmitter release but not MTA-induced neurite retraction in sensory neurons

Abstract

Peripheral neuropathy is a dose-limiting side effect of anticancer treatment with the microtubule-targeted agents (MTAs), paclitaxel and epothilone B (EpoB); however, the mechanisms by which the MTAs alter neuronal function and morphology are unknown. We previously demonstrated that paclitaxel alters neuronal sensitivity, in vitro, in the presence of nerve growth factor (NGF). Evidence in the literature suggests that NGF may modulate the neurotoxic effects of paclitaxel. Here, we examine whether NGF modulates changes in neuronal sensitivity and morphology induced by paclitaxel and EpoB. Neuronal sensitivity was assessed using the stimulated release of calcitonin gene-related peptide (CGRP), whereas morphology of established neurites was evaluated using a high content screening system. Dorsal root ganglion cultures, maintained in the absence or presence of NGF, were treated from day 7 to day 12 in culture with paclitaxel (300 nM) or EpoB (30 nM). Following treatment, the release of CGRP was stimulated using capsaicin or high extracellular potassium. In the presence of NGF, EpoB mimicked the effects of paclitaxel: capsaicin-stimulated release was attenuated, potassium-stimulated release was slightly enhanced and the total peptide content was unchanged. In the absence of NGF, both paclitaxel and EpoB decreased capsaicin- and potassium-stimulated release and the total peptide content, suggesting that NGF may reverse MTA-induced hyposensitivity. Paclitaxel and EpoB both decreased neurite length and branching, and this attenuation was unaffected by NGF in the growth media. These differential effects of NGF on neuronal sensitivity and morphology suggest that neurite retraction is not a causative factor to alter neuronal sensitivity.

A Comparative Study between the Effect of Nerve Growth Factor and All-Trans Retinoic Acid versus their combined use on Taxol Induced Peripheral Neuropathy in Adult Male Albino Rat

“…This could be due to insufficient duration and /or dose of NGF to reverse these changes. In accordance to these findings it was reported that NGF could induce axonal extension and branching and protect against some of the toxic neuronal sensitivity changes without reversing the morphological changes [40] .…”

“…ATRA is capable of regulating the expression of not only NGF but also other neurotrphopins, such as ciliary neurotrophic factor, neurotrophin-3, and brain-derived neurotrophic factor, which could participate in nerve regeneration [48] . It might also overlap the disability of NGF to improve the retraction or degeneration of sensory neurons by its effect on Schwann cells as previously mentioned [40] . Moreover ATRA could regulate actin polymerization in microtubules that disturbed by taxol by transcription of the neurotrophin receptor genes [49] .…”

“…These results were in accordance with Kehong et al (2014) who found that rats treated with low and high doses of NGF faster sensory nerve conduction velocity in a cisplatin model of CIPN [11] . However it was reported that NGF ameliorated sensory neuropathy while not prevent motor one in diabetic rats [39,40] .…”

Proteasome activation by insulin-like growth factor-1/nuclear factor erythroid 2-related factor 2 signaling promotes exercise-induced neurogenesis

“…Immunostaining and quantitative image analysis were performed as previously described [26][27][28] (see Supporting Information for details).…”

Curative effect of surgery combined with nerve growth factor preparation treatment of acute cerebral hemorrhage

“…Mouse nerve growth factor is a cytokine with nerve repair function, its biological function is similar to human nerve growth factor, and it can not only promote the neuron regeneration, survival, proliferation and differentiation, but is also conducive to nerve fiber growth and nerve injury repair [8][9]. In clinical practice, mouse nerve growth factor preparation is widely used in the treatment of diabetic peripheral neuropathy, acute spinal cord injury, optic nerve injury and other neurological lesions [10][11][12], and it is less reported in the rehabilitation treatment after acute cerebral hemorrhage. In the following study, the effect of surgery combined with nerve growth factor preparation treatment of acute cerebral hemorrhage on nerve cytokines and nerve injury was analyzed.…”