PT  - JOURNAL ARTICLE
AU  - Judi Kohn
AU  - Raquel S. Aloyz
AU  - Jean G. Toma
AU  - Mary Haak-Frendscho
AU  - Freda D. Miller
TI  - Functionally Antagonistic Interactions between the TrkA and p75 Neurotrophin Receptors Regulate Sympathetic Neuron Growth and Target Innervation
AID  - 10.1523/JNEUROSCI.19-13-05393.1999
DP  - 1999 Jul 01
TA  - The Journal of Neuroscience
PG  - 5393--5408
VI  - 19
IP  - 13
4099  - http://www.jneurosci.org/content/19/13/5393.short
4100  - http://www.jneurosci.org/content/19/13/5393.full
SO  - J. Neurosci.1999 Jul 01; 19
AB  - In this report, we provide evidence that NGF and BDNF have functionally antagonistic actions on sympathetic neuron growth and target innervation, with NGF acting via TrkA to promote growth and BDNF via p75NTR to inhibit growth. Specifically, in cultured sympathetic neurons that themselves synthesize BDNF, exogenous BDNF inhibits and function-blocking BDNF antibodies enhance process outgrowth. Both exogenous and autocrine BDNF mediate this effect via p75NTR because (1) BDNF does not inhibit growth of neurons lacking p75NTR, (2) function-blocking p75NTR antibodies enhance NGF-mediated growth, and (3) p75NTR−/− sympathetic neurons grow more robustly in response to NGF than do their wild-type counterparts. To determine the physiological relevance of this functional antagonism, we examined the pineal gland, a well defined sympathetic target organ. BDNF is present in the pineal gland during target innervation, and incoming sympathetic axons are p75NTR positive. Moreover, the pineal glands of BDNF+/− and BDNF−/−mice are hyperinnervated with sympathetic fibers, and tyrosine hydroxylase (TH) levels are elevated. Increased tyrosine hydroxylase is also observed in the BDNF+/− carotid artery, another sympathetic neuron target. Thus, BDNF, made by sympathetic neurons and/or their target organs, acts via p75NTR to antagonize NGF-mediated growth and target innervation, suggesting that sympathetic target innervation is determined by the balance of positively and negatively acting neurotrophins present in developing and potentially mature targets.