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Target Concepts:
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Query: UNIPROT:P01178 (
oxytocin
)
15,767
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Perinatal administration of serotonin (5HT) agonist 5-methoxytryptamine (5MT) induces developmental hyperserotonemia (
DHS
; elevated blood serotonin) and produces behavioral and neurochemical changes in rats relevant to Autism Spectrum Disorder (ASD), such as
oxytocin
dysregulation. Disruption of the
oxytocin
system may underlie many of the social deficits present in ASD individuals, thus we investigated the mechanism(s) underlying
DHS
-induced
oxytocin
dysregulation. The most parsimonious mechanism of 5HT action would be alteration of 5HT receptors on
oxytocin
cells; 5HT is known to influence cell survival as well as influence
oxytocin
release via 5HT
1A
and 5HT
2A
receptors, which co-localize in
oxytocin
-expressing (OXT+) cells in the paraventricular nucleus (PVN) of the hypothalamus. We report that both male and female
DHS
rats have a lower percentage of OXT+ cells co-localized with excitatory 5HT
2A
receptors than control animals, while only
DHS
females have a higher percentage of OXT+ cells co-localized with inhibitory 5HT
1A
receptors compared to controls. Importantly,
DHS
also reduces the number of OXT+ cells in the PVN of adult male, but not female, rats. This pattern suggests that females, but not males, can regulate 5HT receptors in response to
DHS
in a manner that promotes
oxytocin
cell survival and functional efficiency. In addition, it has been previously reported that
DHS
alters normal juvenile play, especially in males, thus we also tested play partner preference among juvenile control and
DHS
males. Sex differences observed using the
DHS
model of ASD add to its validity, given the pronounced male sex bias in the prevalence of ASD, and emphasize the need for inclusion of both sexes in ASD research.
...
PMID:Serotonin receptor regulation as a potential mechanism for sexually dimorphic oxytocin dysregulation in a model of Autism. 3004 Sep 18
