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

Sherry K. Pittman, Neilia G. Gracias, Jill Fehrenbacher

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)104-115
Number of pages12
JournalExperimental Neurology
Volume279
DOIs
StatePublished - May 1 2016

Fingerprint

Nerve Growth Factor
Sensory Receptor Cells
Neurites
Microtubules
Paclitaxel
Neurotransmitter Agents
Capsaicin
Potassium
Calcitonin Gene-Related Peptide
Peptides
Spinal Ganglia
Peripheral Nervous System Diseases
epothilone B
Growth

Keywords

  • Chemotherapy-induced peripheral neuropathy
  • Epothilone B
  • Microtubule
  • Nerve growth factor
  • Neurite outgrowth
  • Neuropeptide
  • Paclitaxel
  • Retraction
  • Sensory neuron

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

Cite this

Nerve growth factor alters microtubule targeting agent-induced neurotransmitter release but not MTA-induced neurite retraction in sensory neurons. / Pittman, Sherry K.; Gracias, Neilia G.; Fehrenbacher, Jill.

In: Experimental Neurology, Vol. 279, 01.05.2016, p. 104-115.

Research output: Contribution to journalArticle

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