Neuronal-glial plasticity in gonadotropin-releasing hormone release in adult female rats: role of the polysialylated form of the neural cell adhesion molecule

Abstract

The gonadotropin-releasing hormone (GnRH) neurosecretory system undergoes marked structural and functional changes during the ovarian cycle. The aim of this study was to examine the neuroanatomical relationship between GnRH neurons and a polysialylated form of neural cell adhesion molecule (PSA-NCAM), a known marker of neuronal plasticity. Using immunohistofluorescent dual labeling, we determined that axon terminals of GnRH in the median arcuate nucleus (ME-ARC) region of the hypothalamus in the proestrous phase of the estrous cycle were intimately associated with PSA-NCAM. To further examine whether PSA-NCAM expression associated with GnRH neuron terminals varies in conjugation with cyclic changes in ovarian steroid hormone levels, we examined GnRH and PSA-NCAM dual expression in ovariectomized (OVX) and estrogen-progesterone-primed OVX (EBP-OVX) rats. The expression of PSA-NCAM immunoreactivity associated with the GnRH neurons in the proestrous phase and EBP-OVX rats was significantly higher than during the diestrous phase and in OVX rats where GnRH secretion declines. We further examined whether the structural changes in GnRH axon terminals in the ME-ARC region are also associated with glial plasticity. By extension and retraction of the glial processes, the GnRH neuron terminals in the ME-ARC region could undergo dynamic plastic changes that control GnRH release during the proestrous phase. PSA-NCAM expression was also seen on glial cells in the ME-ARC region. The close association between PSA-NCAM on GnRH and glial cells in the ME-ARC region of the hypothalamus in the rat showed dynamic structural changes in GnRH neuron terminals during the estrous cycle. These observations suggested that PSA-NCAM may act as a molecular substrate to promote neuroplastic changes in the GnRH neurosecretory system.

Role of Glia in the Regulation of Gonadotropin-Releasing Hormone Neuronal Activity and Secretion

“…4), with higher levels in proestrous, when estrogen levels peak, than in diestrous, when estrogen levels are low [62,63]. While these observations suggest the possible involvement of PSA-NCAM in the structural neuroglial plasticity modulating GnRH secretion, as elaborated below, the role of this molecule in the regulation of GnRH neuronal activity and/or secretion and its expression by glial cells remain unclear.…”

“…The in situ detection of contactin suggests that this ternary complex promotes astrocyte-GnRH-neuron interactions at the level of their nerve terminals (both those reaching the organum vasculosum of the lamina terminalis in the preoptic region and those in the median eminence) but not their perikarya, which seem to lack contactin expression [65]. Both astrocytes and GnRH neurons express PSA-NCAM [62], a plasma membrane-associated cell adhesion glycoprotein. It is worth noting that while RPTPβ/contactin and SynCAM1 complexes promote cell-cell adhesiveness, the sialylation of NCAM attenuates its adhesive properties, allowing structural remodeling and the movement of cellular elements [61].…”

“…The in vivo manipulation of sex steroid levels demonstrates their stimulatory effect on the hypothalamic expression of TGFα [27], erbB2 and erbB4 [20], oxytocin [37,87,88], the oxytocin receptor [89,90], TGFβ 1 [57] and PSA-NCAM [62]. At least some of these effects may be mediated by a direct action of gonadal steroids on astrocytes, which express steroid receptors [91], since the in vitro treatment of hypothalamic astrocytes with estradiol increases the expression of TGFα [92] and the enzymatic activity of TACE [26].…”

The role of glia in the hypothalamus: implications for gonadal steroid feedback and reproductive neuroendocrine output

“…High immunoreactivity for PSA-N-CAM has also been detected in the region of the GnRH pulse generator of the monkey (Perera et al 1993), a hypothalamic zone in which the number of axo-somatic synapses changes in response to varying gonadal steroid levels (Witkin et al 1991, Perera & Plant 1997. PSA-N-CAM immunoreactivity increases in the median eminence in the proestrus phase of the cycle when compared with the diestrus phase in rats (Kaur et al 2002, Parkash & Kaur 2005. A role for PSA-N-CAM in neuro-glial plasticity that is under the influence of estrogen was suggested by in vitro studies on hypothalamic monolayer cultures.…”

Differential Gene Expression in Gonadotropin-Releasing Hormone Neurons of Male and Metestrous Female Mice

“…Expression of PSA-NCAM was shown on the surface of GnRH neurons in various species, exhibiting photoperiod- and seasonal breeding-dependent IR [107,108] that suggests a functional role of NCAM in the secretory activity of GnRH neurons. During the estrous cycle of the female rat, PSA-NCAM-IR associated with GnRH neurons was significantly higher in proestrus as compared to diestrus, accompanied with structural reorganization of GnRH axon terminals in the ME [109], indicating an estrous cycle-dependent and, presumably, sexually dimorphic regulation of the Ncam1 gene. In the present work, we detected upregulation of the Ncam1 gene in the male GnRH neurons, which in part supports the observed differences in the neuroplastic changes between sexes.…”