The Journal of Neuroscience, November 1, 2002, 22(21):9567-9572
Evidence That Androgen Acts Through NMDA Receptors to
Affect Motoneurons in the Rat Spinal Nucleus of the Bulbocavernosus
Cynthia L.
Jordan1,
Scott E.
Christensen2,
Robert J.
Handa3,
Jennifer
L.
Anderson3,
Wendy A.
Pouliot3, and
S. Marc
Breedlove1
1 Neuroscience Program and Psychology Department,
Michigan State University, East Lansing, Michigan 48824, 2 Department of Psychology, University of California,
Berkeley, Berkeley, California 94720-1650, and 3 Department
of Anatomy and Neurobiology, Colorado State University, Fort Collins,
Colorado 80523
In adult male rats, spinal nucleus of the bulbocavernosus (SNB)
motoneurons shrink after castration and are restored in size after
androgen treatment. Sixty-day-old Sprague Dawley males were castrated
and implanted with SILASTIC capsules containing testosterone (T) or
nothing, and osmotic minipumps continuously infusing MK-801, a
noncompetitive NMDA receptor antagonist, or saline. Twenty-five days
later, bulbocavernosus muscles were injected with the retrograde tracer
cholera toxin-horseradish peroxidase conjugate (CT-HRP) to label SNB
cells. As seen previously, among saline-treated rats, SNB somata of
T-treated castrates were significantly larger than those of castrates
receiving blank capsules (p < 0.0001).
MK-801 treatment blocked this effect of T on the SNB. MK-801 had no
effect on non-androgen-responsive spinal motoneurons in the neighboring retrodorsolateral nucleus (RDLN), nor did the drug affect SNB soma size
in the absence of androgen treatment. Motoneuronal soma size in Nissl
stain revealed the same pattern of results seen with CT-HRP fills.
In situ hybridization indicated that SNB motoneurons express mRNA for the NMDA receptor subunits R1, R2a, and R2b. Castration reduced the expression of R1 mRNA in SNB motoneurons, an
effect that was blocked by androgen replacement in castrates. R2A and
R2B mRNA expression in SNB cells was not affected by androgen manipulations. Likewise, androgen manipulations had no effect on the
expression of any NMDA receptor subtypes in RDLN motoneurons. These
results suggest that androgen affects the size of SNB motoneurons by
influencing their expression of the NMDA receptor, and therefore the
response of the motoneurons to endogenous glutamate.
Key words:
spinal nucleus of the bulbocavernosus; neural plasticity; NMDA receptor; androgen; motoneurons; MK-801
Copyright © 2002 Society for Neuroscience 0270-6474/02/22219567-06$05.00/0