The Journal of Neuroscience, June 15, 2001, 21(12):4366-4372
Blockade of Endogenous Neurotrophic Factors Prevents the
Androgenic Rescue of Rat Spinal Motoneurons
Jun
Xu1,
Karen M.
Gingras1,
Lynn
Bengston1,
Annalise
Di
Marco2, and
Nancy G.
Forger1
1 Center for Neuroendocrine Studies and Department of
Psychology, University of Massachusetts, Amherst, Massachusetts 01003, and 2 Instituto di Ricerche di Biologia Molecolare
P. Angeletti (IRBM), 00040 Pomezia, Rome, Italy
Target-derived neurotrophic factors are assumed to regulate
motoneuron cell death during development but remain unspecified. Motoneuron cell death in the spinal nucleus of the bulbocavernosus (SNB) of rats extends postnatally and is controlled by androgens. We
exploited these features of the SNB system to identify endogenously produced trophic factors regulating motoneuron survival. Newborn female
rat pups were treated with the androgen, testosterone propionate, or
the oil vehicle alone. In addition, females received trophic factor
antagonists delivered either into the perineum (the site of SNB target
muscles) or systemically. Fusion molecules that bind and sequester the
neurotrophins (trkA-IgG, trkB-IgG, and trkC-IgG) were used to block
activation of neurotrophin receptors, and AADH-CNTF was used to
antagonize signaling through the ciliary neurotrophic factor
receptor-
(CNTFR). An acute blockade of trkB, trkC, or
CNTFR prevented the androgenic sparing of SNB motoneurons when
antagonists were delivered to the perineum. Trophic factor antagonists
did not significantly reduce SNB motoneuron number when higher doses
were injected systemically. These findings demonstrate a requirement
for specific, endogenously produced trophic factors in the androgenic
rescue of SNB motoneurons and further suggest that trophic factor
interactions at the perineum play a crucial role in masculinization of
this neural system.
Key words:
motoneuron; cell death; androgen; neurotrophin; ciliary
neurotrophic factor; trk receptor
Copyright © 2001 Society for Neuroscience 0270-6474/01/21124366-07$05.00/0
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