Morphofunctional plasticity in the adult hypothalamus induces regulation of polysialic acid-neural cell adhesion molecule through changing activity and expression levels of polysialyltransferases

Polysialic acid-neural cell adhesion molecule (PSA-NCAM) expression in the adult nervous system is restricted to regions retaining a capacity for morp hological plasticity. For the female rat hypothalamoneurohypophysial system (HNS), we have previously shown that lactation induces a dramatic decrease in PSA-NCAM, while leaving the level of total NCAM protein unchanged. Here , we wanted to elucidate the molecular mechanisms leading to a downregulati on of PSA, thereby stabilizing newly established synapses and neurohemal co ntacts that accompany the increased activity of oxytocinergic neurons. Firs t, we show that the overall specific activity of polysialyl-transferases pr esent in tissue extracts from supraoptic nuclei decreases by similar to 50% during lactation. So far, two polysialyl-transferase enzymes, STX and PST, have been characterized for their capacity to transfer PSA onto NCAM in vi tro. Using a competitive RT-PCR on RNA extracts from the HNS, we demonstrat e furthermore a significant decrease in the expression levels of both STX a nd PST mRNAs in lactating versus virgin animals. Interestingly, this downre gulation of NCAM polysialylation is not correlated with the post-transcript ional regulation of variable alternative spliced exon splicing, in contrast to neural development. The control of polysialylation via a regulation of both enzyme activity and expression underlines the important role of this p ost-translational modification of NCAM in morphofunctional plasticity in ad ult brain.