Gender and age affect NK1 receptors in the human brain - a positron emission tomography study with [18F]SPA-RQ.
Substance P (SP) is a neurotransmitter and neuromodulator that mediates its effects in the brain predominantly via the neurokinin-1 receptors (NK1Rs). NK1Rs and SP have been shown clinically to be involved in nausea and emesis after chemotherapy (CINV) and have been implicated preclinically in a range of neuropsychiatric disorders but unlike CINV their blockade in these conditions does not have proven clinical value. We investigated whether age and gender affects NK1R binding potential (NK1R-BP; an index of receptor availability) in the living human brain using PET and [18F]SPA-RQ, a highly specific NK1R antagonist. Forty-five healthy volunteers (35 male and 10 female), aged between 19 and 55 years were studied. NK1R-BP was estimated using the simplified reference tissue model with cerebellum as a reference region. A regression analysis indicated that that a loss of NK1R is associated with normal ageing as shown by decreased NK1R-BP (average rate 7% per decade). Statistically significant negative associations between age and NK1R-BP were observed in temporal, parietal and frontal cortex, hippocampus and parahippocampal formation. In addition preliminary data were obtained suggesting possible gender differences in NK1R-BP in the cortex and putamen with females having a lower NK1R-BP. The exact physiological significance of these results remains to be elucidated but conceptually they could be involved in age-related CNS disorders or those with gender differences in prevalence.
Turku PET Centre, Neuropsychiatric Imaging, Turku, Finland.
Mikko J
MJ
Nyman
Olli
O
Eskola
Jaana
J
Kajander
Tero
T
Vahlberg
Sandra
S
Sanabria
Donald
D
Burns
Richard
R
Hargreaves
Olof
O
Solin
Jarmo
J
Hietala
D000328:Adult; D000375:Aging / Q000378:metabolism*; D001921:Brain / Q000000981:diagnostic imaging*; D001923:Brain Chemistry / Q000502:physiology*; D001931:Brain Mapping; D004298:Dopamine / Q000502:physiology; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000138:chemical synthesis; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis; D018040:Receptors, Neurokinin-1 / Q000378:metabolism*; D012044:Regression Analysis; D012727:Sex Characteristics; D013373:Substance P / Q000378:metabolism; D013777:Tetrazoles / Q000138:chemical synthesis
C517420:(2-fluoromethoxy-5-(5-trifluoromethyltetrazol-1-yl)benzyl)(2-phenylpiperidin-3-yl)amine; D010880:Piperidines; D019275:Radiopharmaceuticals; D018040:Receptors, Neurokinin-1; D013777:Tetrazoles; D013373:Substance P; D004298:Dopamine