Glial cell line-derived neurotrophic factor is a survival factor for isolectin B4-positive, but not vanilloid receptor 1-positive, neurons in the mouse.
Most, if not all, nociceptor sensory neurons are dependent on nerve growth factor (NGF) during early embryonic development. A large subpopulation of these sensory neurons loses NGF dependency between embryonic day 16 and postnatal day 14 and become responsive to glial cell line-derived growth factor (GDNF), a member of the transforming growth factor beta (TGF-beta) family. To examine the survival and phenotypic effects of GDNF on sensory neurons in vivo, we generated transgenic mice that overexpress GDNF in the skin. GDNF-overexpresser mice had increased numbers of small unmyelinated sensory neurons that express the tyrosine kinase receptor Ret and bind the plant isolectin B4 (IB4). Surprisingly, in wild-type and transgenic mice, few ( approximately 2%) IB4-positive neurons expressed the vanilloid receptor VR1, a heat-sensitive receptor expressed by many IB4-positive neurons of the rat. Thus, in mouse, GDNF-dependent IB4-positive neurons must use a non-VR1 heat receptor. In addition, the behavior of GDNF-overexpresser animals to noxious heat or mechanical stimuli was indistinguishable from wild-type animals, indicating that, on a behavioral level, peripherally applied GDNF does not alter the sensitivity of the somatosensory system.
Zwick
Melissa
M
Department of Anatomy, University of Kentucky School of Medicine, Lexington, Kentucky 40536, USA.
Davis
Brian M
BM
Woodbury
C Jeffrey
CJ
Burkett
John N
JN
Koerber
H Richard
HR
Simpson
James F
JF
Albers
Kathryn M
KM
D000818:Animals; D001369:Axons / Q000502:physiology / Q000648:ultrastructure; D001522:Behavior, Animal; D015740:Calcitonin Gene-Related Peptide / Q000096:biosynthesis; D002454:Cell Differentiation; D002470:Cell Survival / Q000187:drug effects; D005727:Ganglia, Spinal / Q000166:cytology / Q000502:physiology; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006358:Hot Temperature; D006801:Humans; D037102:Lectins / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D009475:Neurons, Afferent / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D010147:Pain Measurement; D017288:Pain Threshold / Q000502:physiology; D010525:Peripheral Nerves / Q000166:cytology / Q000502:physiology; D010812:Physical Stimulation; D012333:RNA, Messenger / Q000096:biosynthesis; D011955:Receptors, Drug / Q000096:biosynthesis*; D018048:Receptors, Purinergic P2 / Q000096:biosynthesis; D058477:Receptors, Purinergic P2X3; D012867:Skin / Q000294:innervation; D050916:TRPV Cation Channels; D019076:Transgenes
C495039:GDNF protein, human; C495040:Gdnf protein, mouse; D051100:Glial Cell Line-Derived Neurotrophic Factor; D037102:Lectins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; C546407:P2RX3 protein, human; C546409:P2rx3 protein, mouse; C546410:P2rx3 protein, rat; D012333:RNA, Messenger; D011955:Receptors, Drug; D018048:Receptors, Purinergic P2; D058477:Receptors, Purinergic P2X3; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D015740:Calcitonin Gene-Related Peptide