Introduction 5HT role as a differentiation signal in the development of
Brain Research 883 2000 1–14 www.elsevier.com locate bres
Research report
Neuroglial interactions in a model of para-chlorophenylalanine- induced serotonin depletion
´ ´
Alberto Javier Ramos, Patricia Tagliaferro, Ester Marıa Lopez, Jorge Pecci Saavedra, Alicia Brusco
´ Instituto de Biologıa Celular y Neurociencia
‘‘Prof. Eduardo De Robertis’’, Facultad de Medicina, Universidad de Buenos Aires, Paraguay
2155 1121, Buenos Aires, Argentina Accepted 15 August 2000
Abstract
Serotonin 5HT is involved in the development and plasticity of the CNS through the release of S-100b, a glial trophic factor which stabilizes synapses and neuronal cytoskeleton and promotes neuronal development. S-100b 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 depletion induced by 14 days of treatment with
1A
para-chlorophenylalanine PCPA in adult rats. S-100b, 5HT, 5HT-transporter 5HT-T and neurofilaments Nf-200 and Nf-68 expressions were studied by immunohistochemistry and image analysis in striatum, hippocampus, parietal and frontal cortex. Immediately
after ending PCPA treatment we found increased intracellular S-100b immunoreactivity in glial cells, reduced 5HT immunolabelling, reduced density of 5HT-T, Nf-200 and Nf-68 fibers and morphological alterations in neuronal cytoskeleton. One week after PCPA
treatment S-100b immunoreactivity decreased towards control levels, 5HT was normalized in dorsal raphe nucleus, but not in innervation areas; 5HT-T, Nf-200 and Nf-68 fiber densities increased but some neuronal cytoskeletal alterations were still present in striatum. Two
weeks after PCPA treatment S-100b had returned to control levels in most studied regions; 5HT immunoreactivity was normalized, meanwhile 5HT-T, Nf-200 and Nf-68 fiber densities increased reaching values over the control level. We propose that S-100b could be
accumulated in glial cells during the 5HT depletion period, to be released once 5HT levels have recovered. Neuronal cytoskeletal alterations and reduced fiber density may be the expression of decreased extracellular availability of S-100b. Conversely, increased
5HT-T, Nf-200 and Nf-68 expressions, once S-100b is normalized, may be the biological response to the growth factor release.
2000
Elsevier Science B.V. All rights reserved.
Theme : Development and regeneration
Topic : Neurotrophic factors: biological effects
Keywords : Serotonin; Parachlorophenylalanine; Neurotrophic factor; S-100b; Neurofilament; Serotonin transporter