Serotonin depletion in the adult rat produces differential changes in highly polysialylated form of neural cell adhesion molecule and tenascin-C immunoreactivity

Levels of immunoreactivity for highly polysialylated neural cell adhesion m olecule (PSA-NCAM), NCAM, and tenascin-C (TN-C), were examined in the basal ganglia regions and hypothalamic nuclei of adult rats after serotonergic ( 5-HT) lesions induced by 5,7-dihydroxytryptamine injections in the dorsal a nd medial raphe nuclei. Decreases in the density of serotonin fibers were a ssociated with no changes in NCAM and general decreases in PSA-NCAM stainin g, the time-course of changes being selective for each region. Taken that t he confocal analysis indicated that serotonin neurons do not express PSA-NC AM and that similar decreases in PSA-NCAM staining were observed after inhi bition of 5-HT synthesis induced by parachlorophenylalanine administration, these results suggest that 5-HT may reduce adhesion by acting on PSA-NCAM expression in its environment, and thus facilitate plasticity in adult brai n,Two months after the neurotoxin lesions, a normalization of PSA-NCAM stai ning was associated with a partial restoration in 5-HT fiber density in the nucleus accumbens and the supraoptic nucleus, suggesting that PSA-NCAM may facilitate sprouting of 5-HT fibers. Since a similar normalization was als o detected in the suprachiasmatic nucleus, which remained deprived of serot onin fibers, negative factors are likely to be involved in regeneration pro cesses, Indeed, increases in glial fibrillary acidic protein (GFAP) followe d by increases in TN-C were observed in these areas, suggesting that the se cretion of TN-C by astrocytes may have negative consequences on the sprouti ng of 5-HT fibers. Finally, the lack of changes in striatal PSA-NCAM or TN- C staining observed after selective lesions of the dopaminergic pathway ind uced by intranigral injections of 6-hydroxydopamine indicates that 5-HT has a selective and critical role in adult brain plasticity. (C) 1999 Wiley-Li ss, Inc.