Research article summary (published 30 Jul 2009):

Sex influences the effect of a lifelong increase in serotonin transporter function on cerebral metabolism.

Full Abstract

Polymorphic variation in the human serotonin transporter (SERT; 5-HTT) gene resulting in a lifelong increase in SERT expression is associated with reduced anxiety and a reduced risk of affective disorder. Evidence also suggests that sex influences the effect of this polymorphism on affective functioning. Here we use novel transgenic mice overexpressing human SERT (hSERT OVR) to investigate the possible influence of sex on the alterations in SERT protein expression and cerebral function that occur in response to increased SERT gene transcription. SERT binding levels were significantly increased in the brain of hSERT OVR mice in a region-dependent manner. The increased SERT binding in hSERT OVR mice was more pronounced in female than in male mice. Cerebral metabolism, as reflected by a quantitative index of local cerebral glucose utilization (iLCMRglu), was significantly decreased in many brain regions in hSERT OVR female as compared with wild-type female mice, whereas there was no evidence for a significant effect in any region in males. The ability of hSERT overexpression to modify cerebral metabolism was significantly greater in females than in males. This effect was particularly pronounced in the medial striatum, globus pallidus, somatosensory cortex, mamillary body, and ventrolateral thalamus. Overall, these findings demonstrate that the influence of a lifelong increase in SERT gene transcription on cerebral function is greater in females than in males and may relate, in part, to the influence of sex on genetically driven increases in SERT protein expression. Copyright 2009 Wiley-Liss, Inc.

Author information

Author/s: Dawson, Neil (N); Ferrington, Linda (L); Olverman, Henry J (HJ); Harmar, Anthony J (AJ); Kelly, Paul A T (PA);

Affiliation: Centres for Cognitive and Neural Systems, University of Edinburgh, Scotland. N.dawson(-atsign-)ed.ac.uk

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Journal of neuroscience research (J Neurosci Res), published in United States. (Language: eng)

Reference: 2009-Aug; vol 87 (issue 10) : pp 2375-85

Dates: Created 2009/06/15; Completed 2009/08/31;

PMID: 19326435, status: MEDLINE (last retrieval date: 8/31/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Analysis of Variance Animals Binding Sites - drug effects; physiology Blood Glucose - physiology Carbon Isotopes - metabolism Cerebral Cortex - anatomy & histology; metabolism Female Glucose - metabolism Humans Male

Male Mice Mice, Inbred C57BL Mice, Transgenic Paroxetine - pharmacokinetics Protein Binding Serotonin Plasma Membrane Transport Proteins - genetics; metabolism Serotonin Uptake Inhibitors - pharmacokinetics Sex Characteristics Tissue Distribution - drug effects

Associated Chemicals: Blood Glucose (0) ; Carbon Isotopes (0) ; Serotonin Plasma Membrane Transport Proteins (0) ; Serotonin Uptake Inhibitors (0) ; Glucose (50-99-7) ; Paroxetine (61869-08-7)

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