Linked Life Data

15541874

Source:http://linkedlifedata.com/resource/pubmed/id/15541874

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2004-11-15
pubmed:abstractText
Brain alpha2-adrenergic receptors (alpha2-ARs) have been implicated in the regulation of anxiety, which is associated with stress. Environmental treatments during neonatal development could modulate the level of brain alpha2-AR expression and alter anxiety in adults, suggesting possible involvement of these receptors in early-life programming of anxiety state. The present study was undertaken to determine whether the reduction of the expression of A subtype of these receptors most abundant in the neonatal brain affects anxiety-related behavior in adulthood. We attenuated the expression of alpha2A-ARs during neonatal life by two different sequence specific approaches, antisense technology and RNA interference. Treatment of rats with the antisense oligodeoxynucleotide or short interfering RNA (siRNA) against alpha2A-ARs on the days 2-4 of their life, produced a marked acute decrease in the levels of both alpha2A-AR mRNA and [3H]RX821002 binding sites in the brainstem into which drugs were injected. The decrease of alpha2A-AR expression in the neonatal brainstem influenced the development of this receptor system in the brain regions as evidenced by the increased number of [3H]RX821002 binding sites in the hypothalamus of adult animals with both neonatal alpha2A-AR knockdown treatments; also in the frontal cortex of antisense-treated, and in the hippocampus of siRNA-treated adult rats. These adult animals also demonstrated a decreased anxiety in the elevated plus-maze as evidenced by an increased number of the open arm entries, greater proportion of time spent in the open arms, and more than a two-fold increase in the number of exploratory head dips. The results provide the first evidence that the reduction in the brain expression of a gene encoding for alpha2A-AR during neonatal life led to the long-term neurochemical and behavioral alterations. The data suggests that alterations in the expression of the receptor-specific gene during critical periods of brain development may be involved in early-life programming of anxiety-related behavior.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0306-4522
pubmed:author
pubmed:issnType
Print
pubmed:volume
129
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
521-8
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:15541874-Adrenergic alpha-Antagonists, pubmed-meshheading:15541874-Analysis of Variance, pubmed-meshheading:15541874-Animals, pubmed-meshheading:15541874-Animals, Genetically Modified, pubmed-meshheading:15541874-Animals, Newborn, pubmed-meshheading:15541874-Anxiety, pubmed-meshheading:15541874-Behavior, Animal, pubmed-meshheading:15541874-Blotting, Southern, pubmed-meshheading:15541874-Brain Stem, pubmed-meshheading:15541874-Gene Expression Regulation, Developmental, pubmed-meshheading:15541874-Idazoxan, pubmed-meshheading:15541874-Maze Learning, pubmed-meshheading:15541874-Norepinephrine, pubmed-meshheading:15541874-Oligodeoxyribonucleotides, Antisense, pubmed-meshheading:15541874-Protein Binding, pubmed-meshheading:15541874-RNA, Messenger, pubmed-meshheading:15541874-RNA, Small Interfering, pubmed-meshheading:15541874-Radioligand Assay, pubmed-meshheading:15541874-Rats, pubmed-meshheading:15541874-Rats, Wistar, pubmed-meshheading:15541874-Receptors, Adrenergic, alpha-2, pubmed-meshheading:15541874-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:15541874-Tritium
pubmed:year
2004
pubmed:articleTitle
Attenuation of alpha2A-adrenergic receptor expression in neonatal rat brain by RNA interference or antisense oligonucleotide reduced anxiety in adulthood.
pubmed:affiliation
Institute of Cytology and Genetics, Lavrentjev Av. 10, Novosibirsk 630090, Russia.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't