Overexpression of S100β in transgenic mice does not protect from serotonergic denervation induced by 5,7-dihydroxytryptamine

C. Bendotti, S. E. Cole, M. Gobbi, C. Hohmann, R. H. Reeves

Research output: Contribution to journalArticle

Abstract

Transgenic mice overexpressing S100β 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 S100β 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 S100β 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 S100β-overexpressing transgenic mice. Quantitative analysis of the density of 5-HT transporter sites using [3H]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 [3H]citalopram binding was seen between transgenic and control mice. In conclusion, this study demonstrates that constitutive overexpression of S100β 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.

Original languageEnglish
Pages (from-to)501-510
Number of pages10
JournalJournal of Neuroscience Research
Volume67
Issue number4
DOIs
Publication statusPublished - Feb 15 2002

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5,7-Dihydroxytryptamine
Denervation
Transgenic Mice
Serotonin
Citalopram
Prosencephalon
Brain
Middle Hypothalamus
Serotonergic Neurons
Messenger RNA
Injections
In Situ Hybridization

Keywords

  • Neurotoxins
  • Neurotrophic factors
  • Serotonergic neurotoxicity
  • Sprouting

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Overexpression of S100β in transgenic mice does not protect from serotonergic denervation induced by 5,7-dihydroxytryptamine. / Bendotti, C.; Cole, S. E.; Gobbi, M.; Hohmann, C.; Reeves, R. H.

In: Journal of Neuroscience Research, Vol. 67, No. 4, 15.02.2002, p. 501-510.

Research output: Contribution to journalArticle

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abstract = "Transgenic mice overexpressing S100β 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 S100β 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 S100β 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 S100β-overexpressing transgenic mice. Quantitative analysis of the density of 5-HT transporter sites using [3H]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 [3H]citalopram binding was seen between transgenic and control mice. In conclusion, this study demonstrates that constitutive overexpression of S100β 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.",
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