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

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.

Neurogenesis of the sexually dimorphic vasopressin cells of the bed nucleus of the stria terminalis and amygdala of rats.

The bed nucleus of the stria terminalis (BNST) and centromedial amygdala share many neuroantomical and neurochemical characteristics, suggesting similarities in their development. Here we compare the neurogenesis of a group of cells for which already several common characteristics have been documented, that is, the sexually dimorphic arginine vasopressin-immunoreactive (AVP-ir) cells of the BNST and amygdala. To determine when these cells are born, pregnant rats received intraperitoneal injections of the thymidine analogue bromo-2-deoxy-5-uridine (BrdU) on one of nine embryonic days, E10 to E18; E1 being the day that a copulatory plug was found. At 3 months of age, the offsprings of these females were killed and their brains stained immunocytochemically for BrdU and AVP. Most AVP-ir cells were labeled with BrdU by injections on E12 and E13. Although BrdU labeling of AVP-ir cells did not differ between the BNST and amygdala, it differed between males and females. From E12 to E13, the percentage of BrdU-labeled AVP-ir cells decreased more in males than in females. AVP-ir cells appeared to be born earlier than most other cells in the same area, the majority of which were labeled with BrdU by injections on E14, E15, and E16. The similarities in the birthdates of AVP-ir cells in the BNST and amygdala may help to explain why these cells take on so many similar characteristics. The sex difference in birthdates of AVP-ir cells may help to explain which cellular processes underlie the sexual differentiation of these cells.

Importance of target innervation in recovery from axotomy-induced loss of androgen receptor in rat perineal motoneurons.

In adult male rats, axotomy of the spinal nucleus of the bulbocavernosus (SNB) motoneurons transiently down-regulates androgen receptor (AR) immunoreactivity. The present study investigates the importance of target reinnervation in the recovery of AR expression in axotomized SNB motoneurons after short (up to 5 days) and long (1 to 6 weeks) periods of recovery. In the long-term recovery experiment, animals were divided into two groups. In one, the two stumps of the cut pudendal nerve, which carries the axons of the SNB motoneurons, were sutured together immediately after axotomy. In the second group, the proximal stump was ligated immediately after axotomy to prevent target reinnervation. Axotomy of the SNB motoneurons caused a significant down-regulation in AR immunoreactivity within 3 days. At 6 weeks, AR immunoreactivity was still depressed in ligated animals but had recovered to control levels in resutured animals. The recovery in the resutured group was coincident with the first signs of reinnervation of the target perineal muscles, although reinnervation seemed to lag behind AR immunoreactivity. SNB soma size was significantly reduced 2 weeks after axotomy and returned to control levels after 6 weeks of recovery only in the resutured animals. These findings suggest that the target perineal muscles play a role in the regulation of AR expression and androgen sensitivity in the SNB motoneurons, perhaps mediated by muscle-derived trophic factors.

Decline of vasopressin immunoreactivity and mRNA levels in the bed nucleus of the stria terminalis following castration.

Vasopressinergic (VP) neurons in the bed nucleus of the stria terminalis (BNST) of the rat are regulated by gonadal steroids. Gonadectomy causes the projections of the BNST to lose their VP immunoreactivity gradually over a period lasting more than 2 months. Here we have compared the rate of decline of VP mRNA and VP immunoreactivity in the BNST of adult male rats following castration. In experiment 1, the peak number of VP-immunoreactive cells and the level of VP gene expression were compared in sham-operated controls and at 1, 3, or 8 weeks postcastration. The number of VP-immunoreactive cells was not decreased at 1 week postcastration but was significantly reduced (p less than 0.0001) at 3 and 8 weeks postcastration. VP gene expression declined more rapidly, and both the total number of labeled cells (p less than 0.0001) and the average number of grains per cell (p less than 0.01) were significantly reduced by 1 week postcastration. No VP-expressing cells were detectable at 3 or 8 weeks. The difference in the rate of decline in the number of cells labeled by the two techniques following castration did not appear to be due to colchicine pretreatment. In experiment 2, VP mRNA in the BNST was compared in sham-operated controls or at 1, 3, or 7 d postcastration. A significant decrease (p less than 0.01) in the average number of grains per cell was detectable by just 1 d following castration, and the number of labeled cells was significantly reduced (p less than 0.001) by 3 d postcastration.(ABSTRACT TRUNCATED AT 250 WORDS)

Fiber outgrowth from fetal vasopressin neurons of the suprachiasmatic nucleus, bed nucleus of the stria terminalis, and medial amygdaloid nucleus transplanted into adult Brattleboro rats.

Outgrowth of fibers from different types of vasopressin (AVP) neurons was compared in the brains of AVP-deficient Brattleboro rats. Fetal grafts of the suprachiasmatic nucleus (SCN), the bed nucleus of the stria terminalis (BST), and the medial amygdaloid nucleus (MA) were implanted into the lateral ventricle. AVP-immunoreactive fibers from all grafts entered the host tissue in the lateral septum. SCN fibers were confined to the lateral margin of the septum. In contrast, MA and BST fibers formed equally dense networks spanning the width of the lateral septum. The data suggest that these transplanted neurons show specific outgrowth, and that the phylogenetically related BST and MA neurons follow similar cues to reach their targets.

Sex differences in hormonal responses of vasopressin pathways in the rat brain.

Vasopressin (AVP) immunoreactivity in cells and projections of the bed nucleus of the stria terminalis (BST) and medial amygdaloid nucleus (MA) depends on gonadal steroids. In addition, the AVP projections from the BST show denser fiber staining in males than in females. To study whether these differences depend on different hormone levels in adulthood, male and female rats were gonadectomized and similarly treated with testosterone for 4 weeks prior to sacrifice. Immunocytochemistry showed that males had significantly more AVP-immunoreactive (AVP-IR) cells in the BST and significantly denser AVP-IR projections from this nucleus to the lateral septum, lateral habenular nucleus, and periaqueductal central gray than did females. The number of AVP-IR cells in the MA nucleus was not statistically different, but denser AVP-IR fiber networks were found in the MA and ventral hippocampus, which receives its input from the MA. No differences were found in the anteroventral portion of the periventricular nucleus and the dorsomedial nucleus of the hypothalamus that receive their AVP innervation from the suprachiasmatic nucleus. These results indicate that the sex difference in the steroid-sensitive AVP pathways depends on other factors besides circulating hormone levels in adulthood.