Evidence That Androgen Acts Through NMDA Receptors to Affect Motoneurons in the Rat Spinal Nucleus of the Bulbocavernosus

Abstract

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.

Androgen-sensitivity of somata and dendrites of spinal nucleus of the bulbocavernosus (SNB) motoneurons in male C57BL6J mice

“…The relative decrease in BC/LA muscle and seminal vesicle mass after adult castration are comparable to previous findings in both mice and rats (Wainman & Shipounoff, 1941;Park et al, 2002;Forger & Breedlove 1987;Jordan et al, 2002).…”

“…We compared AR expression in SNB motoneurons to two other groups of motoneurons in the same spinal segments: the retrodorsolateral nucleus (RDLN), and the dorsolateral nucleus (DLN). The RDLN motoneurons, which innervate muscles of the foot (Leslie et al, 1991), are largely hormone insensitive (Jordan et al, 2002) and are therefore often used as a control when determining the hormone sensitivity of SNB motoneurons. DLN motoneurons are moderately hormonesensitive (Jordan et al, 1982) and innervate the ischiocavernosus muscles (McKenna & Nadelhaft, 1986), and are also involved in copulatory reflexes in rodents (Sachs, 1982).…”

Androgen-Dependent Regulation of Brain-Derived Neurotrophic Factor and Tyrosine Kinase B in the Sexually Dimorphic Spinal Nucleus of the Bulbocavernosus

“…Autocrine activity of dendritic BDNF occurs via activation of its receptor at the same dendrites, which in turn, phosphorylates postsynaptic N-methyl-d-aspartate (NMDA)-subtype receptors and enhances excitatory signaling (55)(56)(57). BDNF may act via similar pathways in SNB motoneurons to maintain their dendrites and synapses, given that they have glutamatergic inputs, pre-and postsynaptic trkB receptors, NMDA receptors (28), and BDNF-containing dendrites. Moreover, many of these components are influenced by androgens in the SNB system (1,4,28,33).…”

“…BDNF may act via similar pathways in SNB motoneurons to maintain their dendrites and synapses, given that they have glutamatergic inputs, pre-and postsynaptic trkB receptors, NMDA receptors (28), and BDNF-containing dendrites. Moreover, many of these components are influenced by androgens in the SNB system (1,4,28,33).…”

“…We analyzed both SNB motoneurons and motoneurons of the retrodorsolateral nucleus (RDLN) using a ϫ4 oil immersion objective. The RDLN motoneurons that innervate foot muscles serve as an excellent internal control when studying the SNB because they are present in the same sections as SNB motoneurons and are relatively unresponsive to androgens (27,28). Briefly, we first set a threshold that digitally highlighted pixels corresponding to silver grains (autoradiographic signal for BDNF and/or trkB mRNA).…”