Correlation between NGF-dependent, capsaicin-sensitive, and neuropeptide-containing sensory neurons in the adult rat : a review of our recent studies

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There is a line of evidence suggesting that nerve growth factor (NGF) and related members of the neurotrophin family, such as brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), play important roles in the survival, neurite outgrowth and phenotypic expression of various types of neurons. including primary sensory neurons. The actions of these factors are thought to be mediated via specific high affinity receptors (trkA, trkB, trkC, respectively) and low affinity neurotrophin receptors (LANR), and via retrograde transport from target tissues to the cell body. We demonstrated that 35-40% of dorsal root ganglion (DRG) neurons (L4-5) express trkA mRNA (small sized neurons), 5-10% of DRG neurons express trkB mRNA (medium sized) and 15-20% of DRG neurons were trkC mRNA positive (large sized). These neurons constituted different subpopulations and considered to play different roles in the sensory system. All of these trk expressing neurons were LANR positive. Sensory neurons actively synthesizing substance P (SP) or calcitonin gene-related peptide (CGRP) were positive to trkA. It is still unknown if it also affects the production of these peptides at the genetic level, while systemic capsaicin in adult rats is known to reduce substance P and somatostatin in primary sensory nerves. Therefore, we examined the effects of systemically administered capsaicin on the expression of the βpreprotachykinin, γpreprotachykinin, somatostatin, calcitonin gene-related peptide, vasoactive intestinal polypeptide, galanin, neuropeptide Y,and the neurotrophin receptor family genes in dorsal root ganglion neurons by in situ hybridization in adult rats. Nerve growth factor is thought to be involved in the regulation of some of these genes. In the control animals, βpreprotachykinin, γpreprotachvkinin, calcitonin gene-related peptide, somatostatin mRNAs were found in about 30%, 30%, 40%, and 10% of the lumber DRG neurons, respectively. The number of neurons expressing β/γ preprotachykinin mRNA and calcitonin gene-related peptide mRNA decreased to about 50% and 70% of the control values, respectively, 6 days after subcutaneous administration of capsaicin (950 mg/kg). Simultaneously, the number of trkA mRNA-expressing neurons also decreased to about 70% of the control level, while the number of neurons expressing trkB mRNA and trkC mRNA was unaffected. 0n the other hand, vasoactive intestinal polypeptide and galanin mRNAs, but not neuropeptide Y mRNA, began to be expressed in about 10% of the dorsal root ganglion neurons after administration of capsaicin, although their mRNAs were not detected in the controls. However, the expression of somatostatin mRNA was unaffected by the systemic administration of capsaicin. The somatostatin mRNA was not co-expressed with vasoactive intestinal polypeptide and galanin mRNAs in the sensory neurons of rats given capsaicin. Electron-microscopic analysis revealed a few degenerating unmyelinated afferents in sural nerves of the treated rats. The number of small-sized DRG cells labeled with fluoro-gold, a retrograde-tracing dye which was injected into the sural nerve of the treated rats, decreased to half of the control number.These results suggested that systemic administration of capsaicin in adult rats depresses the expression of β/γ preprotachykinin, calcitonin gene-related penticle and trkA mRNAs, and induces expression of vasoactive intestinal polypeptide and galanin mRNAs in sensory neurons, which may be due to the capsaicin-induced degeneration of a subpopulation of sensory afferents. We also demonstrated that the regulation of somatostatin gene expression in mature sensory neurons is not affected by the systemic capsaicin.
関西鍼灸大学の論文
1998-06-30

Correlation between NGF-dependent, capsaicin-sensitive, and neuropeptide-containing sensory neurons in the adult rat : a review of our recent studies

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