Serotonergic reinnervation reverses lesion-induced decreases in PSA-NCAM labeling and proliferation of hippocampal cells in adult rats

Serotonin (5-HT) is believed to play a role in structural plasticity in the adult brain, and cell adhesion molecules may be involved in such adaptive processes. The present study sought to determine the effects of 5-HT denerv ation and reinnervation of the hippocampal formation on the expression of g lial and neuronal markers and neurogenesis in adult rats. Injections of 5,7 -dihydroxytryptamine (5,7-DHT) in the dorsal and medial raphe nuclei, produ cing a partial loss of 5-HT neurons, induced rapid and transient increases in glial fibrillary acidic protein immunoreactivity indicative of a reactiv e gliosis, but no changes in the S100 beta or tenascin-C normally secreted by astroglial cells. In contrast, as long as the hippocampal formation was deprived of 5-HT innervation, significant decreases were observed in the nu mber of granule cells expressing the highly polysialylated form of the neur al cell adhesion molecule (PSA-NCAM) as well as the PSA-NCAM staining of th e hilus in the dentate gyrus. Similar decreases in the number of newly gene rated granule cells labeled with bromodeoxyuridine were also detected durin g this time. All these effects were reversed later, when the hippocampal fo rmation was reinnervated by 5-HT fibers. These results indicate that 5-HT i s one factor which may regulate the number of granule cells proliferating i n the adult dentate gyrus and thereafter expressing PSA-NCAM immunoreactive at the level of cell bodies,dendrites, and axonal paths (mossy fibers). Th ey emphasize the critical role played by 5-HT in the neuronal organization of the hippocampus. Hippocampus 2000;10:37-46. (C) 2000 Wiley-Liss, Inc.