Brain-derived neurotrophic factor regulates expression of androgen receptors in perineal motoneurons

Abstract

Motoneurons in the spinal nucleus of the bulbocavernosus (SNB) express androgen receptors and innervate striated muscles attached to the penis. Previous studies indicated that androgen receptor immunoreactivity in the SNB motoneurons decreases after axotomy and returns to normal only in motoneurons allowed to reinnervate their muscle targets, suggesting that neuron-target interactions play a role in regulating steroid receptor expression in the central nervous system. This study demonstrates that (i) silencing the SNB neuromuscular system with tetrodotoxin did not affect androgen receptor expression in these motoneurons, suggesting that the regulation of androgen receptor is activity-independent; (ii) disruption of axonal transport with vinblastine caused a down-regulation of androgen receptor expression in the SNB motoneurons; and (iii) treatment with brain-derived neurotrophic factor, but not ciliary neurotrophic factor, neurotrophin-4, or glial cell line-derived neurotrophic factor, reversed the axotomy-induced down-regulation of androgen receptor expression. These findings demonstrate neurotrophin regulation of steroid receptor expression in the central nervous system in vivo.

Figure 1

Composite photomicrograph showing ARir (dark nuclear stain) in SNB motoneurons in two horizontal rows, counterstained with cresyl violet (gray cytoplasm). (A) TTX treatment did not affect ARir on the treated side (bottom row) compared with the control side. (B) In contrast, VBL treatment caused a significant decrease in ARir on the treated side (bottom row) compared with the control side. Note the absence of dense nuclear labeling in motoneurons on the treated side of the cord. (C) Compared with PBS (top row), treatment of axotomized motoneurons with BDNF (bottom row) significantly attenuated the decrease in ARir after axotomy. Note the paucity of dense nuclear labeling on the PBS-treated side compared with the BDNF-treated side. (Bar = 100 μm.)

Figure 2

TTX treatment of SNB motoneurons did not affect the density of ARir on the treated side (filled bar) compared with the contralateral control side (hatched bar) and the saline-treated control group.

Figure 3

VBL treatment caused a significant drop in the density of ARir on the treated side (filled bar) compared with the intact contralateral control side (hatched bar) and the saline-treated control group. ∗, P < 0.0001.

Figure 4

After unilateral axotomy, treatment with BDNF, but not with PBS, CNTF, or NT-4, or no treatment, prevented the axotomy-induced decrease in ARir. ∗, P < 0.05; filled bar, treatment; hatched bar, control.

Figure 5

After bilateral axotomy, the density of ARir was higher on the BDNF-treated side compared with the PBS-treated control side (P < 0.03). Filled bar, treatment; hatched bar, PBS. There was no significant difference in the density of ARir between the untreated side and the PBS-treated control side. GDNF caused a significant drop in the density of ARir on the treated side compared with the PBS-treated control side. ∗, Significant difference (P < 0.05).