Cholinergic activity of aged rhesus monkeys revealed by positron emission tomography

Voytko, Mary Lou; Mach, Robert H.; Gage, H. Donald; Ehrenkaufer, Richard L.; Efange, Simon M. N.; Tobin, Joseph R.

doi:10.1002/1098-2396(20010101)39:1<95::aid-syn12>3.0.co;2-2

Cited by 28 publications

(10 citation statements)

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“…Rhesus monkeys are considered to serve as a useful model for normal human aging [58] because aged nonhuman primates show many of the age-related behavioral [4,21,37,38] and neurobiological alterations, such as changes in neurons, dendrites and synapses, and in neurotransmitter and brain metabolite concentrations [6,20,37,58,59], that also have been reported in aging humans. Rhesus monkeys in laboratory conditions can reach the age of 35-40 years and may be considered as old when they are between 20 and 25 years.…”

Section: Introductionmentioning

confidence: 99%

Preservation of hippocampal neuron numbers in aged rhesus monkeys

Keuker

Luiten

Fuchs

2003

Neurobiology of Aging

122

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Preservation of hippocampal neuron numbers in aged rhesus monkeys Keuker, J.I.H.; Luiten, P.G.M.; Fuchs, E. Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum. AbstractTo investigate whether or not aging of nonhuman primates is accompanied by a region-specific neuron loss in the hippocampal formation, we used the optical fractionator technique to obtain stereological estimates of unilateral neuron numbers of the hippocampi of eight young (0-4 years) and five aged (18-31 years) male rhesus monkeys (Macaca mulatta). Our results show a preservation of neurons (mean × 10 3 ± S.D. × 10 3 ) in the subiculum (young = 588 ± 124, aged = 612 ± 207), CA1 (young = 1051 ± 249, aged = 1318 ± 311), CA2 (young = 100 ± 18, aged = 113 ± 12), CA3 (young = 478 ± 125, aged = 509 ± 139), hilus (young = 337 ± 115, aged = 394 ± 90), and dentate gyrus (young = 5550 ± 1725, aged = 7799 ± 2087) of the hippocampal formation. These results confirm a previous stereological study in rhesus monkeys, but are in conflict with data for humans, showing age-dependent region-specific alterations in the hippocampal formation.

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Section: Introductionmentioning

confidence: 99%

Preservation of hippocampal neuron numbers in aged rhesus monkeys

Keuker

Luiten

Fuchs

2003

Neurobiology of Aging

122

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“…In addition to mAChR, VAChT‐PET has been expected to be useful for neuropathological research as well as therapeutic drug development for AD. However, only one PET study using (+)‐4[ 18 F]fluorobenzyltrozamicol ((+)‐[ 18 F]FBT) (Efange et al, ) has been reported regarding age‐related changes in VAChT activity in the brain of non‐human primate, showing a reduction in VAChT levels in the monkey brain with increasing age from 10 to 37 years old (Voytko et al, ). However, the same group recently described that, because the poor selectivity of (+)‐[ 18 F]FBT over sigma receptors resulted in unacceptably high nonspecific binding in human subjects, this PET probe was proven not to be clinically useful for imaging VAChT (Tu et al, ).…”

Section: Discussionmentioning

confidence: 99%

Development of novel PET probe [¹¹C](R,R)HAPT and its stereoisomer [¹¹C](S,S)HAPT for vesicular acetylcholine transporter imaging: A PET study in conscious monkey

Nishiyama

Ohba

Kobashi

et al. 2014

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Carbon-11-labeled (R,R)trans-8-methyl-2-hydroxy-3-[4-[2-aminophenyl]piperizinyl]-tetralin ([(11)C](R,R)HAPT) and its stereoisomer [(11)C](S,S)HAPT were developed for imaging vesicular acetylcholine transporters (VAChTs), exclusively located in presynaptic cholinergic neurons. Both positron emission tomography (PET) probes were evaluated in the brain of conscious monkey (Macaca mulatta) using high-resolution PET. Time-activity curves (TACs) of [(11)C](R,R)HAPT peaked within 5 min after the injection in all regions except the caudate and putamen, both of which showed peaks around 20 min postinjection. The regional distribution patterns of [(11)C](R,R)HAPT determined as total distribution volume (V(t)) were highest in the putamen, high in the caudate, intermediate in the amygdala, hippocampus, and thalamus, lower in the cingulate gyrus and frontal, temporal, and occipital cortices, and lowest in the cerebellum. In contrast, the distribution and TACs of [(11)C](S,S)HAPT were homogeneous in all regions. The uptake of [(11)C](R,R)HAPT was reduced by 1 mg/kg (-)-vesamicol, a specific VAChT antagonist, in all regions except the cerebellum, but not by 0.1 mg/kg SA4503, a specific sigma-1 receptor agonist. These results well reflect the in vitro affinity assessments using rat cerebral membranes. They also demonstrate that [(11)C](R,R)HAPT is a potential PET probe for noninvasive and quantitative imaging of VAChT in the living brain.

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“…The higher resolution and the decreased study duration of PET are definite reasons to consider planning future studies with [ 18 F]fluoroethoxybenzovesamicol, ((−)‐[ 18 F]FEOBV), (−)‐( 2R,3R)‐trans ‐2‐hydroxy‐3‐(4‐phenylpiperidino)‐5‐(2‐[ 18 F]fluoroethoxy)‐1,2,3,4‐tetralin (Mulholland et al, 1998), [ 18 F] (+)‐4‐fluorobenzyltrozamicol ((+)‐[ 18 F]FBT) (Voytko et al, 2001), and other PET radioligands for the vesicular ACh transporters.…”

Section: Discussionmentioning

confidence: 99%

Correlation of the vesicular acetylcholine transporter densities in the striata to the clinical abilities of women with rett syndrome

Brašić

Bibat

Kumar

et al. 2012

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Rett syndrome (RTT) is a neurodevelopmental disability characterized by mutations in the X-linked methyl-CpG-binding protein 2 (MeCP2) located at the Xq28 region. The severity is modified in part by X chromosomal inactivation resulting in wide clinical variability. We hypothesized that the ability to perform the activities of daily living (ADL) is correlated with the density of vesicular acetylcholine transporters in the striata of women with RTT. The density of the vesicular acetylcholine transporters in the living human brain can be estimated by single-photon emission-computed tomography (SPECT) after the administration of (−)-5-[123I]iodobenzovesamicol ([123I]IBVM). Twenty-four (24) hours following the intravenous injection of approximately 333 MBq (9 mCi) [123I]IBVM, four women with RTT and nine healthy adult volunteer control participants underwent SPECT brain scans for sixty (60) minutes. The Vesicular Acetylcholine Transporter Binding Site Index (VATBSI) (Kuhl et al., 1994), a measurement of the density of vesicular acetylcholine transporters, was estimated in the striatum and the reference structure, the cerebellum. The women with RTT were assessed for certain activities of daily living (ADL). Although striatal VATSBI was not significantly lower in RTT (5.2 ± 0.9) than in healthy adults (5.7 ± 1.6), RTT striatal VATSBI and ADL scores were linearly associated (ADL = 0.89*VATSBI + 4.5; R2=0.93; p<0.01), suggesting a correlation between the ability to perform ADL and the density of vesicular acetylcholine transporters in the striata of women with RTT. [123I]IBVM is a promising tool to characterize the pathophysiological mechanisms of RTT and other neurodevelopmental disabilities.

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Cholinergic activity of aged rhesus monkeys revealed by positron emission tomography

Cited by 28 publications

References 50 publications

Preservation of hippocampal neuron numbers in aged rhesus monkeys

Preservation of hippocampal neuron numbers in aged rhesus monkeys

Development of novel PET probe [¹¹C](R,R)HAPT and its stereoisomer [¹¹C](S,S)HAPT for vesicular acetylcholine transporter imaging: A PET study in conscious monkey

Correlation of the vesicular acetylcholine transporter densities in the striata to the clinical abilities of women with rett syndrome

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Cholinergic activity of aged rhesus monkeys revealed by positron emission tomography

Cited by 28 publications

References 50 publications

Preservation of hippocampal neuron numbers in aged rhesus monkeys

Preservation of hippocampal neuron numbers in aged rhesus monkeys

Development of novel PET probe [11C](R,R)HAPT and its stereoisomer [11C](S,S)HAPT for vesicular acetylcholine transporter imaging: A PET study in conscious monkey

Correlation of the vesicular acetylcholine transporter densities in the striata to the clinical abilities of women with rett syndrome

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Development of novel PET probe [¹¹C](R,R)HAPT and its stereoisomer [¹¹C](S,S)HAPT for vesicular acetylcholine transporter imaging: A PET study in conscious monkey