Intrathecally delivered glial cell line-derived neurotrophic factor produces electrically evoked release of somatostatin in the dorsal horn of the spinal cord.
Glial cell line-derived neurotrophic factor (GDNF) is a trophic factor with an established role in sensory neuron development. More recently it has also been shown to support adult sensory neuron survival and exert a neuroprotective effect on damaged sensory neurons. Some adult small-sized dorsal root ganglion (DRG) cells that are GDNF-sensitive sensory neurons express the inhibitory peptide somatostatin (SOM). Thus, we tested the hypothesis that prolonged GDNF administration would regulate SOM expression in sensory neuron cell bodies in the dorsal root ganglia (DRG) and activity-induced release of SOM from axon terminals in the dorsal horn. Continuous intrathecal delivery of GDNF for 11-13 days significantly increased the number of small DRG cells that expressed SOM. Furthermore, GDNF treatment evoked SOM release in the isolated dorsal horn following electrical stimulation of the dorsal roots that was otherwise undetectable in control rats. Conversely capsaicin-induced release of SOM (EC(50) 50 nM) was not modified by GDNF treatment. These results show that GDNF can regulate central synaptic function in SOM-containing sensory neurons.
Charbel Issa
P
P
Neuroscience Research Centre, Guy's, King's and St Thomas' School of Biomedical Sciences, King's College London, London, UK.
Lever
I J
IJ
Michael
G J
GJ
Bradbury
E J
EJ
Malcangio
M
M
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology; D002211:Capsaicin / Q000494:pharmacology; D029721:Drosophila Proteins; D004558:Electric Stimulation; D004797:Enzyme-Linked Immunosorbent Assay; D005727:Ganglia, Spinal / Q000166:cytology / Q000502:physiology*; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007263:Infusions, Parenteral; D007700:Kinetics; D008297:Male; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D009475:Neurons, Afferent / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D020671:Posterior Horn Cells / Q000187:drug effects / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000378:metabolism; D051096:Proto-Oncogene Proteins c-ret; D051381:Rats; D017208:Rats, Wistar; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis / Q000378:metabolism; D013004:Somatostatin / Q000378:metabolism*; D013373:Substance P / Q000378:metabolism
D029721:Drosophila Proteins; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D011518:Proto-Oncogene Proteins; D013373:Substance P; D013004:Somatostatin; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila; D002211:Capsaicin