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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2007-6-19
pubmed:abstractText
The neurotransmitter 5-HT regulates early developmental processes in the CNS. In the present study we followed the embryonic and postnatal development of serotonergic raphe neurons and catecholaminergic target systems in the brain of 5-HT1A receptor knockout (KO) and overexpressing (OE) in comparison with wild-type (WT) mice from embryonic day (E) 12.5 to postnatal day (P) 15.5. Up to P15.5 no differences were apparent in the differentiation and distribution of serotonergic neurons in the raphe area as revealed by the equal number of serotonergic neurons in the dorsal raphe in all three genotypes. However, the establishment of serotonergic projections to the mesencephalic tegmentum and hypothalamus was delayed at E12.5 in KO and OE animals and projections to the cerebral cortex between E16.5 and E18.5 were delayed in OE mice. This delay was only transient and did not occur in other brain areas including septum, hippocampus and striatum. Moreover, OE mice caught up with WT and KO animals postnatally such that at P1.5 serotonergic innervation of the cortex was more extensive in the OE than in KO and WT mice. Tissue levels of 5-HT and of its main metabolite 5-hydroxyindoleacetic acid as well as 5-HT turnover were considerably higher in brains of OE mice and slightly elevated in KO mice in comparison with the WT, starting at E16.5 through P15.5. The initial differentiation of dopaminergic neurons and fibers in the substantia nigra at E12.5 was transiently delayed in KO and OE mice as compared with WT mice, but no abnormalities in noradrenergic development were apparent in later stages. The present data indicate that 5-HT1A receptor deficiency or overexpression is associated with increased 5-HT synthesis and turnover in the early postnatal period. However, they also show that effects of 5-HT1A KO or OE on the structural development of the serotonergic system are at best subtle and transient. They may nonetheless contribute to the establishment of increased or reduced anxiety-like behavior, respectively, in adult mice.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0306-4522
pubmed:author
pubmed:issnType
Print
pubmed:day
29
pubmed:volume
147
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
388-402
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Embryonic and postnatal development of the serotonergic raphe system and its target regions in 5-HT1A receptor deletion or overexpressing mouse mutants.
pubmed:affiliation
Institute of Pharmacology, Phillippstrasse 12, Dorotheenstrasse 94, D-10117 Berlin, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't