The highly sialylated isoform of the neural cell adhesion molecule is required for estradiol-induced morphological synaptic plasticity in the adult arcuate nucleus

The large quantities of polysialic acid (PSA) characterizing highly sialyla ted isoform of the neural cell adhesion molecule (PSA-NCAM), greatly reduce cell adhesion and render this particular cell surface adhesion molecule a likely candidate to intervene in dynamic neuronal phenomena, such as synapt ic plasticity. The hypothalamic arcuate nucleus expresses high levels of PS A-NCAM and maintains a high capacity for neuroplastic changes in the adult. Thus, in the arcuate nucleus of female rats, varying circulating levels of estrogen give rise to a reversible reduction in the number of axo-somatic GABA synapses, together with a changing ensheathing of neuronal somata by a strocytes. To examine the role of PSA in such changes, we perturbed its exp ression, either by blockade with antibodies raised against this carbohydrat e moiety (delivered intracerebroventricularly), or by its enzymatic cleavag e after microinjection of endoneuraminidase N over the arcuate nucleus. Eit her procedure was performed in ovariectomized adult rats that received conc urrent treatment with 17 beta -estradiol. Morphological synaptic plasticity was analysed using the unbiased disector method to assess synaptic densiti es in ultrathin sections of the arcuate nucleus immunogold-labelled for GAB A. As expected, 17 beta -estradiol induced a significant reduction in the n umber of GABAergic axo-somatic synapses, a reduction which did not occur af ter infusion of anti-PSA antibodies or in vivo enzymatic removal of PSA fro m NCAM. Taken together, our results provide strong evidence that the presen ce of large quantities of the PSA moiety on NCAM is a necessary prerequisit e for estrogen-induced phasic remodelling of synapses in the adult female a rcuate nucleus.