Gender-dependent increases with healthy aging of the human cerebral cannabinoid-type 1 receptor binding using [18F]MK-9470 PET

Laere, Koen Van; Goffin, Karolien; Casteels, Cindy; Dupont, Patrick; Mortelmans, Luc; Hoon, Jan de; Bormans, Guy

doi:10.1016/j.neuroimage.2007.10.053

Cited by 119 publications

(96 citation statements)

References 46 publications

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“…In addition to methodological considerations such as the finite resolution of the PET imaging system, other investigators have commented on possible contributing factors including multiple in vivo affinity states of the receptor and its localization within the cell or its surface as part of a functional receptor reserve or active trafficking between the membrane and intracellular compartments. 10,13,24 Although the exact causes underlying these regionally specific discrepancies remain uncertain, the consistency across different PET radiotracers suggests that the phenomenon is real and warrants further study.…”

Section: Discussionmentioning

confidence: 99%

“…Integrated brain TACs from men had greater numerical mean SUV across all but one region ( Figure 7E) with values 17% higher on average (P o 0.0001 for effect of sex, no interaction between sex and region; no individual regions survived Bonferroni correction), consistent with previous findings obtained using the CB1 PET tracer [ 18 F]MK-9470. 24 Mean values of V T , however, were higher in women across the 17 ROIs examined ( Figure 7F) with an average difference of 23% (P o 0.0001 for effect of gender, no interaction between gender and region in analysis of variance; post hoc testing revealed differences that survived multiple comparison testing in caudate, pallidum, posterior cingulate cortex, and putamen with frontal cortex, hippocampus, and temporal cortex also contributing to global effect with 0.05 o adjusted P o 0.10).…”

Section: Gender Differencesmentioning

confidence: 99%

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Imaging the Cannabinoid CB1 Receptor in Humans with [¹¹C] OMAR: Assessment of Kinetic Analysis Methods, Test–Retest Reproducibility, and Gender Differences

Normandin

Zheng

Lin

et al. 2015

J Cereb Blood Flow Metab

100

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The Radiotracer [ 11 C]OMAR was developed for positron emission tomography (PET) imaging of cannabinoid type-1 receptors (CB1R). The objectives of the present study were to evaluate kinetic analysis methods, determine test-retest reliability, and assess gender differences in receptor availability. Dynamic PET data were acquired in 10 human subjects, and analyzed with one-tissue (1T) and two-tissue (2T) compartment models and by the Logan and multilinear analysis (MA1) methods to estimate regional volume of distribution (V T ). The 2T model inclusive of a vascular component (2T V ) and MA1 were the preferred techniques. Test-retest reliability of V T was good (mean absolute deviation~9%; intraclass correlation coefficient~0.7). Tracer parent fraction in plasma was lower in women (P o 0.0001). Cerebral uptake normalized by body weight and injected dose was higher in men by 17% (P o0.0001), but V T was significantly greater in women by 23% (P o 0.0001). These findings show that [ 11 C]OMAR binding can be reliably quantified by the 2T model or MA1 method and demonstrate the utility of this tracer for in vivo imaging of CB1R. In addition, results from the present study indicate that gender difference in receptor binding should be taken into consideration when [ 11 C]OMAR is used to quantify CB1R availability in neuropsychiatric disorders.

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Section: Discussionmentioning

confidence: 99%

Section: Gender Differencesmentioning

confidence: 99%

Imaging the Cannabinoid CB1 Receptor in Humans with [¹¹C] OMAR: Assessment of Kinetic Analysis Methods, Test–Retest Reproducibility, and Gender Differences

Normandin

Zheng

Lin

et al. 2015

J Cereb Blood Flow Metab

100

View full text Add to dashboard Cite

show abstract

“…On the other hand, he reported a significantly reduced coupling between the receptors and Gi proteins in the limbic forebrain during ageing, which could be responsible for a reduced CB1 receptor signalling even when receptor levels are unchanged. In humans, a sex-dependent increase in CB1 receptor binding during ageing in the basal ganglia, lateral temporal cortex and in limbic areas was reported [227]. Whether the level of endogenous cannabinoids changes in ageing is unclear: some studies have reported diminished anandamide levels during ageing in CB1-receptor-deficient mice [228,229], whereas others found no significant differences in the endocannabinoid levels during ageing in different brain regions in WT or CB1-receptor-deficient mice [226].…”

Section: Cannabinoid System May Change During Ageing In the Brainmentioning

confidence: 99%

The endocannabinoid system in normal and pathological brain ageing

Bilkei-Gorzó

2012

Phil. Trans. R. Soc. B

121

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The role of endocannabinoids as inhibitory retrograde transmitters is now widely known and intensively studied. However, endocannabinoids also influence neuronal activity by exerting neuroprotective effects and regulating glial responses. This review centres around this less-studied area, focusing on the cellular and molecular mechanisms underlying the protective effect of the cannabinoid system in brain ageing. The progression of ageing is largely determined by the balance between detrimental, proageing, largely stochastic processes, and the activity of the homeostatic defence system. Experimental evidence suggests that the cannabinoid system is part of the latter system. Cannabinoids as regulators of mitochondrial activity, as anti-oxidants and as modulators of clearance processes protect neurons on the molecular level. On the cellular level, the cannabinoid system regulates the expression of brainderived neurotrophic factor and neurogenesis. Neuroinflammatory processes contributing to the progression of normal brain ageing and to the pathogenesis of neurodegenerative diseases are suppressed by cannabinoids, suggesting that they may also influence the ageing process on the system level. In good agreement with the hypothesized beneficial role of cannabinoid system activity against brain ageing, it was shown that animals lacking CB1 receptors show early onset of learning deficits associated with age-related histological and molecular changes. In preclinical models of neurodegenerative disorders, cannabinoids show beneficial effects, but the clinical evidence regarding their efficacy as therapeutic tools is either inconclusive or still missing.

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“…Neuroanatomical and positron emission tomography studies have demonstrated that CB 1 receptor mRNA and protein occur in most layers of the human neocortex (Westlake et al, 1994;Lopez de Jesus et al, 2006;van Laere et al, 2008;Eggan et al, 2010). We studied synaptic transmission using patch-clamp electrophysiological methods in cortical tissue removed during neurosurgery to eliminate epileptogenic foci.…”

Section: Introductionmentioning

confidence: 99%

Exogenous and Endogenous Cannabinoids Suppress Inhibitory Neurotransmission in the Human Neocortex

Kovacs

Knop

Urbanski

et al. 2011

Neuropsychopharmacol

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Activation of CB 1 receptors on axon terminals by exogenous cannabinoids (eg, D 9 -tetrahydrocannabinol) and by endogenous cannabinoids (endocannabinoids) released by postsynaptic neurons leads to presynaptic inhibition of neurotransmission. The aim of this study was to characterize the effect of cannabinoids on GABAergic synaptic transmission in the human neocortex. Brain slices were prepared from neocortical tissues surgically removed to eliminate epileptogenic foci. Spontaneous GABAergic inhibitory postsynaptic currents (sIPSCs) were recorded in putative pyramidal neurons using patch-clamp techniques. To enhance the activity of cannabinoidsensitive presynaptic axons, muscarinic receptors were continuously stimulated by carbachol. The synthetic cannabinoid receptor agonist WIN55212-2 decreased the cumulative amplitude of sIPSCs. The CB 1 antagonist rimonabant prevented this effect, verifying the involvement of CB 1 receptors. WIN55212-2 decreased the frequency of miniature IPSCs (mIPSCs) recorded in the presence of tetrodotoxin, but did not change their amplitude, indicating that the neurotransmission was inhibited presynaptically. Depolarization of postsynaptic pyramidal neurons induced a suppression of sIPSCs. As rimonabant prevented this suppression, it is very likely that it was due to endocannabinods acting on CB 1 receptors. This is the first demonstration that an exogenous cannabinoid inhibits synaptic transmission in the human neocortex and that endocannabinoids released by postsynaptic neurons suppress synaptic transmission in the human brain. Interferences of cannabinoid agonists and antagonists with synaptic transmission in the cortex may explain the cognitive and memory deficits elicited by these drugs.

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Gender-dependent increases with healthy aging of the human cerebral cannabinoid-type 1 receptor binding using [18F]MK-9470 PET

Cited by 119 publications

References 46 publications

Imaging the Cannabinoid CB1 Receptor in Humans with [¹¹C] OMAR: Assessment of Kinetic Analysis Methods, Test–Retest Reproducibility, and Gender Differences

Imaging the Cannabinoid CB1 Receptor in Humans with [¹¹C] OMAR: Assessment of Kinetic Analysis Methods, Test–Retest Reproducibility, and Gender Differences

The endocannabinoid system in normal and pathological brain ageing

Exogenous and Endogenous Cannabinoids Suppress Inhibitory Neurotransmission in the Human Neocortex

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Gender-dependent increases with healthy aging of the human cerebral cannabinoid-type 1 receptor binding using [18F]MK-9470 PET

Cited by 119 publications

References 46 publications

Imaging the Cannabinoid CB1 Receptor in Humans with [11C] OMAR: Assessment of Kinetic Analysis Methods, Test–Retest Reproducibility, and Gender Differences

Imaging the Cannabinoid CB1 Receptor in Humans with [11C] OMAR: Assessment of Kinetic Analysis Methods, Test–Retest Reproducibility, and Gender Differences

The endocannabinoid system in normal and pathological brain ageing

Exogenous and Endogenous Cannabinoids Suppress Inhibitory Neurotransmission in the Human Neocortex

Contact Info

Product

Resources

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Imaging the Cannabinoid CB1 Receptor in Humans with [¹¹C] OMAR: Assessment of Kinetic Analysis Methods, Test–Retest Reproducibility, and Gender Differences

Imaging the Cannabinoid CB1 Receptor in Humans with [¹¹C] OMAR: Assessment of Kinetic Analysis Methods, Test–Retest Reproducibility, and Gender Differences