Lack of neurotrophin-4 causes selective structural and chemical deficits in sympathetic ganglia and their preganglionic innervation

Citation
A. Roosen et al., Lack of neurotrophin-4 causes selective structural and chemical deficits in sympathetic ganglia and their preganglionic innervation, J NEUROSC, 21(9), 2001, pp. 3073-3084
Citations number
58
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
JOURNAL OF NEUROSCIENCE
ISSN journal
0270-6474 → ACNP
Volume
21
Issue
9
Year of publication
2001
Pages
3073 - 3084
Database
ISI
SICI code
0270-6474(20010501)21:9<3073:LONCSS>2.0.ZU;2-V
Abstract
Neurotrophin-4 (NT-4) is perhaps the still most enigmatic member of the neu rotrophin family. We show here that NT-4 is expressed in neurons of paraver tebral and prevertebral sympathetic ganglia, i.e., the superior cervical (S CG), stellate (SG), and celiac (CG) ganglion. Mice deficient for NT-4 showe d a significant reduction (20-30%) of preganglionic sympathetic neurons in the intermediolateral column (IML) of the thoracic spinal cord. In contrast , neuron numbers in the SCG, SG, and CG were unchanged. Numbers of axons in the thoracic sympathetic trunk (TST) connecting the SG with lower paravert ebral ganglia were also reduced, whereas axon numbers in the cervical sympa thetic trunk (CST) were unaltered. Axon losses in the TST were paralleled b y losses of synaptic terminals on SG neurons visualized by electron microsc opy. Furthermore, immunoreactivity for the synaptic vesicle antigen SV2 was clearly reduced in the SG and CG. Levels of catecholamines and tyrosine hy droxylase immunoreactivity were dramatically reduced in the SG and the CG b ut not in the SCG. Despite this severe phenotype in the sympathetic system, blood pressure levels were not reduced and displayed a pattern more typica l of deficits in baroreceptor afferents. Numbers of IML neurons were unalte red at postnatal day 4, suggesting a postnatal requirement for their mainte nance. In light of these and previous data, we hypothesize that NT-4 provid ed by postganglionic sympathetic neurons is required for establishing and/o r maintaining synapses of IML neurons on postganglionic cells. Impairment o f synaptic connectivity may consequently reduce impulse flow, causing a red uction in transmitter synthesis in postganglionic neurons.