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

✍ Scribed by Neil Dawson; Linda Ferrington; Henry J. Olverman; Anthony J. Harmar; Paul A. T. Kelly

• Publisher: John Wiley and Sons
• Year: 2009
• Tongue: English
• Weight: 223 KB
• Volume: 87
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/jnr.22062

✦ Synopsis

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 (__h__SERT 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 __h__SERT OVR mice in a region‐dependent manner. The increased SERT binding in __h__SERT 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 __h__SERT 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 __h__SERT 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. © 2009 Wiley‐Liss, Inc.