title: Age and sex effects on 5-HT(4) receptors in the human brain: a [(11)C]SB207145 PET study.
abstract: Experimental studies indicate that the 5-HT(4) 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-HT(4) receptor-binding potentials in striatum, the limbic system, and neocortex. Positron-emission tomographic scans were conducted using the radioligand [(11)C]SB207145 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-HT(4) receptor binding in the limbic system. The lower limbic 5-HT(4) receptor binding in women supports a role for 5-HT(4) 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-HT(4) receptor binding with aging contrasts others in subtypes of receptors, which generally decrease with aging.
authors.affiliation: Neurobiology Research Unit, Department of Neurology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Karine
authors.initials: K
authors.lastname: Madsen
authors.forename: Mette T
authors.initials: MT
authors.lastname: Haahr
authors.forename: Lisbeth
authors.initials: L
authors.lastname: Marner
authors.forename: Sune H
authors.initials: SH
authors.lastname: Keller
authors.forename: William F
authors.initials: WF
authors.lastname: Baaré
authors.forename: Claus
authors.initials: C
authors.lastname: Svarer
authors.forename: Steen G
authors.initials: SG
authors.lastname: Hasselbalch
authors.forename: Gitte M
authors.initials: GM
authors.lastname: Knudsen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010880:Piperidines; D049268:Positron-Emission Tomography; D011485:Protein Binding; D044422:Receptors, Serotonin, 5-HT4 / Q000378:metabolism*; D012737:Sex Factors; D055815:Young Adult
chemical_list: D010880:Piperidines; C534709:SB 207145; D044422:Receptors, Serotonin, 5-HT4