Expression of mRNAs for neurotrophic factors (NGF, BDNF, NT-3, and GDNF) and their receptors (p75 ngfr , TrkA, TrkB, and TrkC) in the adult human peripheral nervous system and nonneural tissues

Abstract

The steady-state mRNA levels of the four neurotrophic factors of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and glial cell line-derived neurotrophic factor (GDNF) and their receptors (p75NGFR, trkA, trkB and trkC) in the adult human peripheral nervous system (PNS) as well as nonneural tissues were examined using quantitative reverse transcription-polymerase chain reaction (RT-PCR). NGF and BDNF mRNA levels were high in the heart and spleen as well as in the dorsal root ganglia (DRG) and spinal cord, showing similar spatial expression patterns, while NT-3 mRNA levels were more pronounced in the liver and spleen. In contrast to these neurotrophins, GDNF mRNA expression occurred at the highest levels in the muscle, and it was also comparatively high in the spinal cord. p75NGFR mRNA was expressed extensively throughout the PNS tissues and in the spleen. The spatial expression patterns differed among trkA, and trkB and trkC mRNAs. trkA mRNA was greatly expressed in the DRG, sympathetic ganglia and spleen, while the trkB and trkC mRNA levels were high in the DRG, spinal cord and brain. The levels of trkB and trkC mRNAs with tyrosine kinase domain, compared to those with extracellular domain, were relatively high in the DRG, whereas they were low in the spinal cord and brain. The spatial patterns of the distributions of neurotrophic factors and their receptors mRNA levels in the adult human PNS and nonneural tissues are largely similar to those reported in other mammals, but these findings provide further, more specific, understanding relevant to the therapeutic approach to human diseases.

Neurotrophic factor in the treatment of Parkinson disease

“…Glial cell line-derived neurotrophic factor is a novel member of the transforming growth factor family and is reported to exhibit trophic factor on embryonic substantia nigra dopaminergic neurons in vitro and possibly in vivo. 1,3,7,9,16,19,20 It may qualify as a highly specific dopaminergic neurotrophic factor with potential therapeutic benefit in the treatment of PD, a neurodegenerative disorder characterized by the loss of dopaminergic neurons in substantia nigra. For these reasons, it is suggested that GDNF exerts long-lasting trophic effects on dopaminergic neurons in vivo and may be useful as a potential therapeutic agent in individuals suffering from PD.…”

Effects of castration on the immunoreactivity to NGF, BDNF and their receptors in the pelvic ganglia of the male rat

“…In addition to their effects in neural survival and differentiation, neurotrophins are now implicated in neurite outgrowth, synaptic plasticity, cell cycle control and apoptosis during adulthood (Schinder and Poo, 2000;Chao, 2003). Furthermore, recent data show that neurotrophins are involved in a variety of biological processes in nonneuronal tissues in humans and other vertebrates (Yamamoto et al, 1996;Sariola, 2001;Leon et al 1994;Rosenbaum et al 1998;Tessarollo, 1998).…”

Searching for common stem cells of the hepatic and hematopoietic systems in the human fetal liver: CD34+ cytokeratin 7/8+ cells express markers for stellate cells

“…4). NGFR, within the liver, has been found on stellate cells (27,28), which prompted us to further investigate desmin expression, an intracytoplasmic protein found in hepatic stellate cells (29).…”

“…Hepatic stellate cells have been shown to be an source of several neurotrophins and express neurotrophin receptors (27,28,39). Although hepatocytes may express low levels of NGFR (40), no other liver cell has been reported to have high expression.…”