Neuroglial interactions in a model of para-chlorophenylalanine-induced serotonin depletion

Serotonin (5HT) is involved in the development and plasticity of the CNS th rough the release of S-100 beta, a glial trophic factor which stabilizes sy napses and neuronal cytoskeleton and promotes neuronal development. S-100 b eta is released from glial cells after activation of glial 5HT,, receptors. We present in this paper the effects upon neurons and glia of a 5HT deplet ion induced by 14 days of treatment with para-chlorophenylalanine (PCPA) in adult rats. S-100 beta, 5HT, 5HT-transporter (5HT-T) and neurofilaments (N f-200 and Nf-68) expressions were studied by immunohistochemistry and image analysis in striatum, hippocampus, parietal and frontal cortex. Immediatel y after ending PCPA treatment we found increased intracellular S-100 beta i mmunoreactivity in glial cells, reduced 5HT immunolabelling, reduced densit y of 5HT-T, Nf-200 and Nf-68 fibers and morphological alterations in neuron al cytoskeleton. One week after PCPA treatment S-100 beta immunoreactivity decreased towards control levels, 5HT was normalized in dorsal raphe nucleu s, but not in innervation areas; 5HT-T, Nf-200 and Nf-68 fiber densities in creased but some neuronal cytoskeletal alterations were still present in st riatum. Two weeks after PCPA treatment S-100 beta had returned to control l evels in most studied regions; 5HT immunoreactivity was normalized, meanwhi le 5HT-T, Nf-200 and Nf-68 fiber densities increased reaching values over t he control level. We propose that S-100P could be accumulated in glial cell s during the 5HT depletion period, to be released once 5HT levels have reco vered. Neuronal cytoskeletal alterations and reduced fiber density may be t he expression of decreased extracellular availability of S-100P. Conversely , increased 5HT-T, Nf-200 and Nf-68 expressions, once S-100 beta is normali zed, may be the biological response to the growth factor release. (C) 2000 Elsevier Science B.V. All rights reserved.