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

Neil Dawson, Linda Ferrington, Henry J Olverman, Anthony J Harmar, Paul A.T Kelly

Research output: Contribution to journalArticle

12 Citations (Scopus)

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.
LanguageEnglish
Pages2375-2385
Number of pages11
JournalJournal of Neuroscience Research
Volume87
Issue number10
DOIs
Publication statusPublished - 2009

Fingerprint

Serotonin Plasma Membrane Transport Proteins
Mammillary Bodies
Genes
Ventral Thalamic Nuclei
Globus Pallidus
Aptitude
Somatosensory Cortex
Brain
Mood Disorders
Transgenic Mice
Anxiety
Glucose

Keywords

  • mice
  • transgenic
  • 2-deoxyglucose
  • anxiety
  • neuroscience

Cite this

Dawson, Neil ; Ferrington, Linda ; Olverman, Henry J ; Harmar, Anthony J ; Kelly, Paul A.T. / Sex influences the effect of a lifelong increase in serotonin transporter function on cerebral metabolism. In: Journal of Neuroscience Research. 2009 ; Vol. 87, No. 10. pp. 2375-2385.
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Sex influences the effect of a lifelong increase in serotonin transporter function on cerebral metabolism. / Dawson, Neil; Ferrington, Linda; Olverman, Henry J; Harmar, Anthony J; Kelly, Paul A.T.

In: Journal of Neuroscience Research, Vol. 87, No. 10, 2009, p. 2375-2385.

Research output: Contribution to journalArticle

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