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Overexpression of S100β in transgenic mice does not protect from serotonergic denervation induced by 5,7‐dihydroxytryptamine
Author(s) -
Bendotti C.,
Cole S.E.,
Gobbi M.,
Hohmann C.,
Reeves R.H.
Publication year - 2002
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.10132
Subject(s) - serotonergic , endocrinology , medicine , genetically modified mouse , biology , basal forebrain , forebrain , lesion , in situ hybridization , 5,7 dihydroxytryptamine , denervation , basal (medicine) , medial forebrain bundle , transgene , serotonin , striatum , central nervous system , messenger rna , receptor , pathology , dopamine , biochemistry , gene , insulin
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 [ 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 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. © 2002 Wiley‐Liss, Inc.