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

Abstract

Levels of immunoreactivity for highly polysialylated neural cell adhesion molecule (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 and medial raphe nuclei. Decreases in the density of serotonin fibers were associated with no changes in NCAM and general decreases in PSA-NCAM staining, the time-course of changes being selective for each region. Taken that the confocal analysis indicated that serotonin neurons do not express PSA-NCAM and that similar decreases in PSA-NCAM staining were observed after inhibition 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 brain. Two months after the neurotoxin lesions, a normalization of PSA-NCAM staining 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 also detected in the suprachiasmatic nucleus, which remained deprived of serotonin fibers, negative factors are likely to be involved in regeneration processes. Indeed, increases in glial fibrillary acidic protein (GFAP) followed by increases in TN-C were observed in these areas, suggesting that the secretion of TN-C by astrocytes may have negative consequences on the sprouting 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 induced by intranigral injections of 6-hydroxydopamine indicates that 5-HT has a selective and critical role in adult brain plasticity.

Chronic Fluoxetine Treatment Increases the Expression of PSA-NCAM in the Medial Prefrontal Cortex

“…General 5-HT depletion also reduces PSA-NCAM expression in the hippocampus, as well as in hypothalamic nuclei and basal ganglia (Brezun and Daszuta, 1999;Brezun and Daszuta, 2000), which indicates a relationship between 5-HT and PSA-NCAM expression. The mPFC receives a dense serotoninergic innervation (Azmitia and Segal, 1978;Steinbusch, 1981) and contains several 5-HT receptor subtypes Pompeiano et al, 1992).…”

“…Moreover, the prefrontal cortex neurons project back to the brain nuclei that synthesize 5-HT, inducing its release (Jankowski and Sesack, 2004;Peyron et al, 1998;Takagishi and Chiba, 1991;Vertes, 2004). Previous reports have already demonstrated a link between PSA-NCAM expression and 5-HT: depletion of 5-HT reduces PSA-NCAM expression in the hippocampus, certain hypothalamic nuclei and the basal ganglia (Brezun and Daszuta, 1999;Brezun and Daszuta, 2000). Although the mechanism by which 5-HT modulates PSA-NCAM expression is not yet known, 5-HT may influence PSA-NCAM expression by acting directly on receptors located in certain neurons.…”

Serotonin: a regulator of neuronal morphology and circuitry

“…Clearly the evidence suggests a role for serotonin receptor-activation and signaling cascades in modulating interneuron migration and axon pathfinding directly. In an alternate view, one study proposes that reducing serotonin levels during development reduces expression of cell adhesion molecules in the brain, which in turn impairs migration and induces deficits in synaptogenesis [48]. Both mechanisms may contribute to morphological aberrations associated with altered serotonin signaling during development.…”

Oppositional effects of serotonin receptors 5-HT1a, 2, and 2c in the regulation of adult hippocampal neurogenesis

“…Serotonin is long known as a potent regulator of adult hippocampal neurogenesis (Brezun and Daszuta, 1999, 2000; Radley and Jacobs, 2002; Santarelli et al, 2003; Banasr et al, 2004), but data on how this stimulation is actually achieved are limited and partially contradictory. Given the controversies over the ideas that adult neurogenesis might underlie the pathogenesis of depression and that adult neurogenesis might be necessary for antidepressant action (Jacobs et al, 2000; D'Sa and Duman, 2002; Sahay and Hen, 2007; Kempermann et al, 2008), the potential role of serotonin-based antidepressants in the regulation of adult neurogenesis have became a matter of broader interest.…”