Experimental studies indicate that the 5-HT4 receptor activation influence cognitive function, affective symptoms, and the development of Alzheimer's disease (AD). The prevalence of AD increases with aging, and women have a higher predisposition to both AD and affective disorders than men. This study aimed to investigate sex and age effects on 5-HT4 receptor-binding potentials in striatum, the limbic system, and neocortex. Positron-emission tomographic scans were conducted using the radioligand 11 CSB207145 in a cohort of 30 healthy subjects (mean age 44 years; range 20 to 86 years; 14 men and 16 women). The output parameter, BP ND, was modeled using the simplified reference tissue model, and partial volume correction was performed with the Muller-Gartner method. A decline with age of 1% per decade was found only in striatum. Women had a 13% lower 5-HT4 receptor binding in the limbic system. The lower limbic 5-HT4 receptor binding in women supports a role for 5-HT4 receptors in the sex-specific differences in emotional control and might contribute to the higher prevalence of affective diseases and AD in women. The relatively stable 5-HT4 receptor binding with aging contrasts others in subtypes of receptors, which generally decrease with aging. © 2011 ISCBFM All rights reserved.
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Madsen, K., Haahr, M. T., Marner, L., Keller, S. H., Baaré, W. F., Svarer, C., … Knudsen, G. M. (2011). Age and sex effects on 5-HT 4 receptors in the human brain: A 11 CSB207145 PET study. Journal of Cerebral Blood Flow and Metabolism, 31(6), 1475–1481. https://doi.org/10.1038/jcbfm.2011.11