Linked Life Data

11978831

Source:http://linkedlifedata.com/resource/pubmed/id/11978831

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2002-4-29
pubmed:abstractText
Serotonergic (5-HT) axons from the raphe nuclei are among the earliest afferents to innervate the developing forebrain. The present study examined whether GAP-43, a growth-associated protein expressed on growing 5-HT axons, is necessary for normal 5-HT axonal outgrowth and terminal arborization during the perinatal period. We found a nearly complete failure of 5-HT immunoreactive axons to innervate the cortex and hippocampus in GAP-43-null (GAP43-/-) mice. Abnormal ingrowth of 5-HT axons was apparent on postnatal day 0 (P0); quantitative analysis of P7 brains revealed significant reductions in the density of 5-HT axons in the cortex and hippocampus of GAP43-/- mice relative to wild-type (WT) controls. In contrast, 5-HT axon density was normal in the striatum, septum, and amygdala and dramatically higher than normal in the thalamus of GAP43-/- mice. Concentrations of serotonin and its metabolite, 5-hydroxyindolacetic acid, and norepinephrine were decreased markedly in the anterior and posterior cerebrum but increased in the brainstem of GAP43-/- mice. Cell loss could not account for these abnormalities, because unbiased stereological analysis showed no significant difference in the number of 5-HT dorsal raphe neurons in P7 GAP43-/- versus WT mice. The aberrant 5-HT innervation pattern persisted at P21, indicating a long-term alteration of 5-HT projections to forebrain in the absence of GAP-43. In heterozygotes, the density and morphology of 5-HT axons was intermediate between WT and homozygous GAP43-/- mice. These results suggest that GAP-43 is a key regulator in normal pathfinding and arborization of 5-HT axons during early brain development.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
22
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3543-52
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11978831-Aging, pubmed-meshheading:11978831-Animals, pubmed-meshheading:11978831-Axons, pubmed-meshheading:11978831-Brain Stem, pubmed-meshheading:11978831-Carrier Proteins, pubmed-meshheading:11978831-Cell Count, pubmed-meshheading:11978831-Cerebral Cortex, pubmed-meshheading:11978831-GAP-43 Protein, pubmed-meshheading:11978831-Heterozygote, pubmed-meshheading:11978831-Hippocampus, pubmed-meshheading:11978831-Homozygote, pubmed-meshheading:11978831-Hydroxyindoleacetic Acid, pubmed-meshheading:11978831-Membrane Glycoproteins, pubmed-meshheading:11978831-Membrane Transport Proteins, pubmed-meshheading:11978831-Mice, pubmed-meshheading:11978831-Mice, Inbred C57BL, pubmed-meshheading:11978831-Mice, Knockout, pubmed-meshheading:11978831-Nerve Tissue Proteins, pubmed-meshheading:11978831-Norepinephrine, pubmed-meshheading:11978831-Prosencephalon, pubmed-meshheading:11978831-Raphe Nuclei, pubmed-meshheading:11978831-Serotonin, pubmed-meshheading:11978831-Serotonin Plasma Membrane Transport Proteins, pubmed-meshheading:11978831-Telencephalon, pubmed-meshheading:11978831-Thalamus
pubmed:year
2002
pubmed:articleTitle
GAP-43 is critical for normal development of the serotonergic innervation in forebrain.
pubmed:affiliation
Department of Cell and Developmental Biology, State University of New York Upstate Medical University, Syracuse, New York 13210, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.