title: Overexpression of S100beta in transgenic mice does not protect from serotonergic denervation induced by 5,7-dihydroxytryptamine.
abstract: Transgenic mice overexpressing S100beta were used to examine whether the chronic elevation of this protein alters the response to selective partial serotonergic lesions produced by bilateral intracerebroventricular injections of 5,7-dihydroxytryptamine (5,7-DHT). Basal levels of S100beta mRNA examined by in situ hybridization were two- to threefold higher throughout the brain in transgenic than in control mice, whereas 5-HT levels in forebrain were similar in both. After the 5,7-DHT-induced lesions, no differences were found in the S100beta mRNA levels in either normal or transgenic mice. At 5 and 60 days after the lesion, forebrain 5-HT levels were reduced by 56% and 35%, respectively, in control mice and by 51% and 35%, respectively, in the transgenic mice. Analysis of the 5-HT immunostaining showed a marked decrease of the immunoreactivity in various brain regions, which was comparable at the two intervals postlesion. One exception was the medial hypothalamus, where an almost complete disappearance of 5-HT immunoreactivity was observed in the medial region at 5 days after lesion, followed by a marked reinnervation 60 days later. These hypothalamic changes were seen in both controls and S100beta-overexpressing transgenic mice. Quantitative analysis of the density of 5-HT transporter sites using [(3)H]citalopram binding, a marker of serotonergic terminals, showed a marked decrease in different brain regions at both 5 and 60 days after 5,7-DHT injections. No difference in basal and postlesion levels of [(3)H]citalopram binding was seen between transgenic and control mice. In conclusion, this study demonstrates that constitutive overexpression of S100beta in transgenic mice does not modify serotonin levels during development, nor does it protect the serotonergic neurons from selective neurotoxicity or modify the serotonergic sprouting induced by partial lesion.
authors.affiliation: Laboratory of Molecular Neurobiology, Mario Negri Institute for Pharmacological Research, Via Eritrea 62, 20157 Milan, Italy. Bendotti@marionegri.it
authors.forename: C
authors.initials: C
authors.lastname: Bendotti
authors.forename: S E
authors.initials: SE
authors.lastname: Cole
authors.forename: M
authors.initials: M
authors.lastname: Gobbi
authors.forename: C
authors.initials: C
authors.lastname: Hohmann
authors.forename: R H
authors.initials: RH
authors.lastname: Reeves
mesh_terms: D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D002352:Carrier Proteins / Q000187:drug effects / Q000378:metabolism; D015283:Citalopram / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000378:metabolism; D026901:Membrane Transport Proteins; D051379:Mice; D008822:Mice, Transgenic; D009414:Nerve Growth Factors / Q000235:genetics* / Q000378:metabolism; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009498:Neurotoxins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D012701:Serotonin / Q000378:metabolism*; D018490:Serotonin Agents / Q000494:pharmacology*; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors / Q000378:metabolism; D014316:Tritium / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology*
chemical_list: D015116:5,7-Dihydroxytryptamine; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D015283:Citalopram; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D009498:Neurotoxins; D012333:RNA, Messenger; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D012701:Serotonin; D018490:Serotonin Agents; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; D014316:Tritium; C493231:Slc6a4 protein, mouse