Effects of NGF overexpression on anatomical and physiological properties of sympathetic postganglionic neurons.
To examine the effects of increased target derived nerve growth factor (NGF) on the sympathetic nervous system, the superior cervical ganglion was characterized in transgenic mice overexpressing NGF in keratinized epithelium (e.g. skin, tongue and oral cavity). In these mice NGF overexpression was achieved via expression of an NGF transgene driven by the K14 keratin promoter. This promoter is expressed at approximately embryonic day 11 and thereafter expressed constitutively in the adult. This expression results in supranormal levels of NGF in targets of sympathetic postganglionic neurons prior to the period of programmed cell death. Examination of postnatal day 6 (PN6) and adult transgenic mice shows ca. 2.5-fold increase in neuron number in the superior cervical ganglion (SCG). Analysis of SCG neuronal size revealed a dramatic hypertrophy in the transgenic mice that is present by PN6 and is maintained in the adult. Intracellular physiological measurements of control superior cervical ganglia identified two distinct types of neurons identified on the basis of their response to depolarizing current; 'phasic' neurons fire a single action potential while 'tonic' neurons fire continuously. In adult transgenic mice the phasic neurons were 102% larger than control phasic neurons while the tonic neurons only increased 44% relative to controls. The hypertrophy of sympathetic ganglia in the transgenic mice was correlated with an increased innervation of skin and dorsal root ganglia, structures that either express the transgene or concentrate NGF produced by the skin.
Davis
B M
BM
Department of Anatomy and Neurobiology, University of Kentucky College of Medicine, Lexington 40536, USA. bmdavi00@pop.uky.edu
Wang
H S
HS
Albers
K M
KM
Carlson
S L
SL
Goodness
T P
TP
McKinnon
D
D
D000818:Animals; D002452:Cell Count; D048429:Cell Size / Q000502:physiology; D004594:Electrophysiology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D009414:Nerve Growth Factors / Q000235:genetics*; D009474:Neurons / Q000166:cytology / Q000201:enzymology / Q000502:physiology*; D017779:Sympathetic Fibers, Postganglionic / Q000166:cytology / Q000502:physiology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D009414:Nerve Growth Factors; D014446:Tyrosine 3-Monooxygenase