Neuroglial interactions in a model of para-chlorophenylalanine-induced serotonin depletion.
Serotonin (5HT) is involved in the development and plasticity of the CNS through the release of S-100beta, a glial trophic factor which stabilizes synapses and neuronal cytoskeleton and promotes neuronal development. S-100beta is released from glial cells after activation of glial 5HT(1A) receptors. We present in this paper the effects upon neurons and glia of a 5HT depletion induced by 14 days of treatment with para-chlorophenylalanine (PCPA) in adult rats. S-100beta, 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-100beta 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-100beta 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-100beta 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-100beta 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-100beta. Conversely, increased 5HT-T, Nf-200 and Nf-68 expressions, once S-100beta is normalized, may be the biological response to the growth factor release.
Ramos
A J
AJ
Instituto de Biología Celular y Neurociencia "Prof. Eduardo De Robertis", Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155 (1121), Buenos Aires, Argentina.
Tagliaferro
P
P
López
E M
EM
Pecci Saavedra
J
J
Brusco
A
A
D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002450:Cell Communication / Q000502:physiology*; D010134:Fenclonine / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D026901:Membrane Transport Proteins; D009414:Nerve Growth Factors / Q000378:metabolism; D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D012701:Serotonin / Q000172:deficiency* / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology*; D050486:Serotonin Plasma Membrane Transport Proteins
D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D012702:Serotonin Antagonists; D050486:Serotonin Plasma Membrane Transport Proteins; C493232:Slc6a4 protein, rat; D012701:Serotonin; D010134:Fenclonine