ABSTRACT
Post-transcriptional modification of the neural cell adhesion molecule (NCAM) by polysialic acid significantly decreases NCAM adhesiveness and more generally modifies cell-cell interactions. Polysialic acid-NCAM (PSA-NCAM) is mainly expressed in the developing nervous system. In the adult, its expression is restricted to regions that retain morphological plasticity, such as the hypothalamo-neurohypophysial system during lactation in rats. Since cell-cell interactions and synaptic contacts in the hypothalamo-neurohypophysial system are greatly increased during lactation, we examined whether PSA-NCAM expression is modified during this period. Immunohistochemistry and immunoblotting showed that, compared with virgin rats, PSA-NCAM dramatically decreased during lactation in both the supraoptic nuclei and the neurohypophysis, and returned to its initial level only after weaning. This decrease was progressive and became significant only at the end of the first week of lactation. By contrast, modifications in the level of NCAM protein or changes in the splicing pattern of NCAM mRNAs could not be detected. The decline in polysialic acid on the NCAM molecule could strengthen membrane appositions, thereby stabilizing the newly established synapses and neurohaemal contacts in the hypothalamo-neurohypophysial system that accompany the increased neuronal activity that occurs during lactation. We also studied the regulation of the phosphorylated microtubule-associated protein-1B (MAP1B-P), whose distribution pattern largely overlaps with that of PSA-NCAM in the adult brain. Expression of MAP1B-P was greatly increased during lactation in the hypothalamic axons projecting into the neurohypophysis. Thus, the expression patterns of both PSA-NCAM and MAP1B-P may reflect the permanent structural plasticity characterizing the hypothalamo-neurohypophysial system in the adult.
Subject(s)
Hypothalamo-Hypophyseal System/physiology , Lactation/physiology , Neural Cell Adhesion Molecules/metabolism , Pituitary Gland, Posterior/physiology , Protein Processing, Post-Translational , Sialic Acids/metabolism , Animals , Axons/physiology , Biomarkers , Female , Microtubule-Associated Proteins/metabolism , Nerve Regeneration/physiology , Neural Cell Adhesion Molecules/biosynthesis , Neuronal Plasticity/physiology , Phosphorylation , RNA, Messenger/biosynthesis , Rats , Rats, WistarABSTRACT
Microtubule-associated protein IB (MAP1B) is the first MAP to be detected in the developing nervous system, and it becomes markedly down-regulated postnatally. Its expression, particularly that of its phosphorylated isoform, is associated with axonal growth. To determine whether adult central nervous system (CNS) areas that retain immunoreactivity for MAP1B are associated with morphological plasticity, we compared the distribution of a phosphorylated MAP1B isoform (MAP1B-P) to the distribution of total MAP1B protein and MAP1B-mRNA. Although they were present only at very low levels, both protein and message were found ubiquitously in almost all adult CNS neurons. The intensity of staining, however, varied markedly among different regions, with only a few nuclei retaining relatively high levels. MAP1B-P was restricted to axons, whereas total MAP1B was present in cell bodies and processes. Relatively to total MAP1B protein and its mRNA, MAP1B-P levels decreased more dramatically with maturation, and they were detectable in only a few specific areas that underwent structural modifications. These included primary afferents and motor neurons, olfactory tubercles, habenular and raphe projections to interpeduncular nuclei, septum, and the hypothalamus. The distribution pattern of MAP1B-P was compared to that of the embryonic N-CAM rich in polysialic acid (PSA-NCAM). We found that the PSA-NCAM immunostaining was largely overlapped with that of MAP1B-P in the adult CNS. These results suggest that, like PSA-NCAM, MAP1B may be one of the molecules expressed during brain development that also plays a role in structural remodeling in the adult.
