Abstract
Adenosine A1 receptors (A1Rs) are widely distributed throughout the entire human brain, while adenosine A2A receptors (A2ARs) are present in dopamine-rich areas of the brain, such as the basal ganglia. A past study using autoradiography reported a reduced binding ability of A1R in the striatum of old rats. We developed positron emission tomography (PET) ligands for mapping the adenosine receptors and we successfully visualized the A1Rs using 8-dicyclopropylmethyl-1-11C-methyl-3-propylxanthine (11C-MPDX). We previously reported that the density of A1Rs decreased with age in the human striatum, although we could not observe an age-related change in A2ARs. The aim of this study was to investigate the age-related change of the density of A1Rs in the thalamus and cerebral cortices of healthy participants using 11C-MPDX PET. We recruited eight young (22.0 ± 1.7 years) and nine elderly healthy male volunteers (65.7 ± 8.0 years). A dynamic series of decay-corrected PET scans was performed for 60 min starting with the injection of 11C-MPDX. We placed the circular regions of interest of 10 mm in diameter in 11C-MPDX PET images. The values for the binding potential (BPND) of 11C-MPDX in the thalamus, and frontal, temporal, occipital, and parietal cortices were calculated using a graphical analysis, wherein the reference region was the cerebellum. BPND of 11C-MPDX was significantly lower in elderly participants than young participants in the thalamus, and frontal, temporal, occipital, and parietal cortices. In the human brain, we could observe the age-related decrease in the distribution of A1Rs.
Highlights
Medical development has increased the average human lifespan (Vaupel, 2010)
We developed ligands for positron emission tomography (PET) to map the adenosine receptors, and successfully visualized the A1 receptors (A1Rs) using 8-dicyclopropylmethyl-1-11C-methyl-3-propylxanthine (11C-MPDX, Figure 1) (Fukumitsu et al, 2005) and the A2A receptors (A2ARs) using [7-methyl-11C]-(E)-8-(3,4,5-trimethoxystyryl)-1,3,7-trimethylxanthine (11C-TMSX) (Ishiwata et al, 2000a,b, 2002)
Using 11C-MPDX and 11C-TMSX PET, we previously reported that the density of A1Rs decreased with age in the human striatum, we could not observe an age-related change in A2ARs (Mishina et al, 2012)
Summary
Medical development has increased the average human lifespan (Vaupel, 2010). Cognitive functions such as memory often decline as humans age (van Geldorp et al, 2015), and aging is the major risk factor for Alzheimer’s disease (Fjell et al, 2014a). In the human brain, neuroimaging studies revealed that endogenous dopamine, and dopamine transporter, D1 and D2 receptors and aromatic L-amino acid decarboxylase decrease with age (Suhara et al, 1991; Reeves et al, 2002; Ishibashi et al, 2009), while monoamine oxidase B increases with age (Reeves et al, 2002). Such age-related decrease has been reported in the cholinergic, glutamatergic and γ-aminobutyric acid (GABA)ergic systems (Segovia et al, 2001; Rissman et al, 2007; Schliebs and Arendt, 2011)
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