Plasticity in rat uterine sympathetic nerves: the role of TrkA and p75 nerve growth factor receptors

Abstract

Uterine sympathetic innervation undergoes profound remodelling in response to physiological and experimental changes in the circulating levels of sex hormones. It is not known, however, whether this plasticity results from changes in the innervating neurons, the neuritogenic properties of the target tissue or both. Using densitometric immunohistochemistry, we analysed the effects of prepubertal chronic oestrogen treatment (three subcutaneous injections of 20 µ g of β -oestradiol 17-cypionate on days 25, 27 and 29 after birth), natural peripubertal transition and late pregnancy (19-20 days post coitum) on the levels of TrkA and p75 nerve growth factor receptors in uterine-projecting sympathetic neurons of the thoraco-lumbar paravertebral sympathetic chain (T7-L2) identified using the retrograde tracer Fluorogold. For comparative purposes, levels of TrkA and p75 were assessed in the superior cervical ganglion (SCG) following prepubertal chronic oestrogen treatment. These studies showed that the vast majority of uterine-projecting neurons expressed both TrkA and p75. Both prepubertal chronic oestrogen treatment and the peripubertal transition increased the ratio p75 to TrkA in uterine-projecting neurons, whereas pregnancy elicited the opposite effect. Prepubertal chronic oestrogen treatment had no effects on levels of TrkA or p75 in sympathetic neurons of the SCG. Taken together, our data suggest that neurotrophin receptor-mediated events may contribute to regulate sex hormone-induced plasticity in uterine sympathetic nerves, and are in line with the idea that, in vivo , plasticity in uterine nerves involves changes in both the target and the innervating neurons.

Long-term Estradiol-17.BETA. Administration Decreases the Number of Neurons in the Caudal Mesenteric Ganglion Innervating the Ovary in Sexually Mature Gilts

“…It seems that E2 could also contribute to the loss of neurons in the porcine CaMG by desensitization of these cells to NGF, which has previously been observed in rat DRG neurons following a single injection [38] and long-term [22] replacement of estrogen. Also, significant reduction in the number of neurons displaying p75 protein has been observed at the end of pregnancy, when estrogen levels are increased [42]. Moreover, considering the expression of ERs by neurons in autonomic and sensory areas of the lumbosacral spinal cord that have connections with female reproductive system [43], it is possible that the reduction in the number of postganglionic neurons found in the present study may partly result from changes of the density of ERs receptors on preganglionic neurons in response to E2 treatment, which could ultimately affect both the morphology and activity of these cells and consequently disturb the neuronal network function.…”

Remodeling of uterine innervation

“…Richeri and co-workers (2005) have observed that the mean size of uterine-projecting sympathetic neurons decreases in pregnant rats. This reduction could reflect the degeneration of sympathetic fibers, or a reduction in neurotrophins or in neurotrophin receptors (Richeri et al 2005). In addition, Klukovits and co-workers (2002) have described a reduction in the number of nerves in pregnant rats by using fluorescence histochemistry.…”

“…Furthermore, in addition to changes in neurotrophic factor availability, sex hormones might regulate plasticity in uterine sympathetic nerves by altering their receptivity to neurotrophins (Richeri et al 2005;Hasan et al 2005).…”

Reduced sympathetic neurite outgrowth on uterine tissue sections from rats treated with estrogen

“…Animals were killed by an overdose of sodium pentobarbital on the day after completion of treatment. This regimen was selected because it provoked a substantial degree of uterine sympathetic denervation and reduced the atrophic changes induced by ovariectomy in the uterus Richeri et al 2005). Vehicle-treated (peanut oil; Sigma-Aldrich, USA) OVX rats were killed 3 days following surgery.…”