scholarly journals Seasonal variation in brain mu-opioid receptor availability

2020 ◽  
Author(s):  
Lihua Sun ◽  
Jing Tang ◽  
Heidi Liljenbäck ◽  
Aake Honkaniemi ◽  
Jenni Virta ◽  
...  
Keyword(s):  
Seasonal Variation ◽  
Opioid Receptor ◽  
Causal Effect ◽  
Brain Regions ◽  
Seasonal Effects ◽  
Positron Emission ◽  
Significant Seasonal Variation ◽  
Normal Humans ◽  
Post Hoc

AbstractSeasonal rhythms influence mood and sociability. The brain μ-opioid receptor (MOR) system modulates a multitude of seasonally varying socioemotional functions, but its seasonal variation remains elusive with no previously reported in vivo evidence. Here, we studied the seasonal effects on brain MOR availability via analysing a dataset (n=204) of [11C]carfentanil positron emission tomography (PET) scans of healthy volunteers. We found that seasonally varying daylength had an inverted U-shaped functional relationship with brain MOR availability. Brain regions sensitive to daylength spanned the socio-emotional brain circuits, where MOR availability formed a spring-like peak. Causal effect of daylength on brain MOR availability was further verified by a post hoc experiment with repeated PET imaging of rats (n=9) under seasonal photoperiodic simulation. Therefore, the in vivo brain MOR availability in normal humans shows significant seasonal variation, which aligns with expected seasonal variation in mood and suicidality.

scholarly journals ADORA2A variation and adenosine A1 receptor availability in the human brain with a focus on anxiety-related brain regions: modulation by ADORA1 variation

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Christa Hohoff ◽  
Tina Kroll ◽  
Baoyuan Zhao ◽  
Nicole Kerkenberg ◽  
Ilona Lang ◽  
...  
Keyword(s):  
Brain Regions ◽  
Phenotypic Characterization ◽  
Gene Variation ◽  
Quantitative Pet ◽  
Positron Emission ◽  
A1 Receptor ◽  
Magnetic Resonance Imaging Mri ◽  
Post Hoc ◽  
The Relationship

AbstractAdenosine, its interacting A1 and A2A receptors, and particularly the variant rs5751876 in the A2A gene ADORA2A have been shown to modulate anxiety, arousal, and sleep. In a pilot positron emission tomography (PET) study in healthy male subjects, we suggested an effect of rs5751876 on in vivo brain A1 receptor (A1AR) availability. As female sex and adenosinergic/dopaminergic interaction partners might have an impact on this rs5751876 effect on A1AR availability, we aimed to (1) further investigate the pilot male-based findings in an independent, newly recruited cohort including women and (2) analyze potential modulation of this rs5751876 effect by additional adenosinergic/dopaminergic gene variation. Healthy volunteers (32/11 males/females) underwent phenotypic characterization including self-reported sleep and A1AR-specific quantitative PET. Rs5751876 and 31 gene variants of adenosine A1, A2A, A2B, and A3 receptors, adenosine deaminase, and dopamine D2 receptor were genotyped. Multivariate analysis revealed an rs5751876 effect on A1AR availability (P = 0.047), post hoc confirmed in 30 of 31 brain regions (false discovery rate (FDR) corrected P values < 0.05), but statistically stronger in anxiety-related regions (e.g., amygdala, hippocampus). Additional effects of ADORA1 rs1874142 were identified; under its influence rs5751876 and rs5751876 × sleep had strengthened effects on A1AR availability (Pboth < 0.02; post hoc FDR-corrected Ps < 0.05 for 29/30 regions, respectively). Our results support the relationship between rs5751876 and A1AR availability. Additional impact of rs1874142, together with rs5751876 and sleep, might be involved in regulating arousal and thus the development of mental disorders like anxiety disorders. The interplay of further detected suggestive ADORA2A × DRD2 interaction, however, necessitates larger future samples more comparable to magnetic resonance imaging (MRI)-based samples.

scholarly journals The pharmacokinetics of [18F]UCB-H revisited in the healthy non-human primate brain

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sébastien Goutal ◽  
Martine Guillermier ◽  
Guillaume Becker ◽  
Mylène Gaudin ◽  
Yann Bramoullé ◽  
...  
Keyword(s):  
Slow Component ◽  
Specific Binding ◽  
Compartment Model ◽  
Brain Regions ◽  
Volume Of Distribution ◽  
Pharmacokinetic Data ◽  
Limited Information ◽  
Positron Emission ◽  
Human Primate

Abstract Background Positron Emission Tomography (PET) imaging of the Synaptic Vesicle glycoprotein (SV) 2A is a new tool to quantify synaptic density. [18F]UCB-H was one of the first promising SV2A-ligands to be labelled and used in vivo in rodent and human, while limited information on its pharmacokinetic properties is available in the non-human primate. Here, we evaluate the reliability of the three most commonly used modelling approaches for [18F]UCB-H in the non-human cynomolgus primate, adding the coupled fit of the non-displaceable distribution volume (VND) as an alternative approach to improve unstable fit. The results are discussed in the light of the current state of SV2A PET ligands. Results [18F]UCB-H pharmacokinetic data was optimally fitted with a two-compartment model (2TCM), although the model did not always converge (large total volume of distribution (VT) or large uncertainty of the estimate). 2TCM with coupled fit K1/k2 across brain regions stabilized the quantification, and confirmed a lower specific signal of [18F]UCB-H compared to the newest SV2A-ligands. However, the measures of VND and the influx parameter (K1) are similar to what has been reported for other SV2A ligands. These data were reinforced by displacement studies using [19F]UCB-H, demonstrating only 50% displacement of the total [18F]UCB-H signal at maximal occupancy of SV2A. As previously demonstrated in clinical studies, the graphical method of Logan provided a more robust estimate of VT with only a small bias compared to 2TCM. Conclusions Modeling issues with a 2TCM due to a slow component have previously been reported for other SV2A ligands with low specific binding, or after blocking of specific binding. As all SV2A ligands share chemical structural similarities, we hypothesize that this slow binding component is common for all SV2A ligands, but only hampers quantification when specific binding is low.

scholarly journals Cellular sources of TSPO expression in healthy and diseased brain

2021 ◽  
Author(s):  
Erik Nutma ◽  
Kelly Ceyzériat ◽  
Sandra Amor ◽  
Stergios Tsartsalis ◽  
Philippe Millet ◽  
...  
Keyword(s):  
Cell Activity ◽  
Brain Regions ◽  
Cellular Level ◽  
Translocator Protein ◽  
Disease Stage ◽  
Animal Models Of Disease ◽  
Positron Emission ◽  
Neuropsychiatric Diseases ◽  
Tspo Expression

AbstractThe 18 kDa translocator protein (TSPO) is a highly conserved protein located in the outer mitochondrial membrane. TSPO binding, as measured with positron emission tomography (PET), is considered an in vivo marker of neuroinflammation. Indeed, TSPO expression is altered in neurodegenerative, neuroinflammatory, and neuropsychiatric diseases. In PET studies, the TSPO signal is often viewed as a marker of microglial cell activity. However, there is little evidence in support of a microglia-specific TSPO expression. This review describes the cellular sources and functions of TSPO in animal models of disease and human studies, in health, and in central nervous system diseases. A discussion of methods of analysis and of quantification of TSPO is also presented. Overall, it appears that the alterations of TSPO binding, their cellular underpinnings, and the functional significance of such alterations depend on many factors, notably the pathology or the animal model under study, the disease stage, and the involved brain regions. Thus, further studies are needed to fully determine how changes in TSPO binding occur at the cellular level with the ultimate goal of revealing potential therapeutic pathways.

Changes in synaptic density in the subacute phase after ischemic stroke: A 11C-UCB-J PET/MR study

2021 ◽  
pp. 0271678X2110477
Author(s):  
Laura Michiels ◽  
Nathalie Mertens ◽  
Liselot Thijs ◽  
Ahmed Radwan ◽  
Stefan Sunaert ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Standardized Uptake Value ◽  
Brain Regions ◽  
Asymmetry Index ◽  
Cerebellar Hemisphere ◽  
Future Research ◽  
Stroke Patients ◽  
Synaptic Density ◽  
Positron Emission

Functional alterations after ischemic stroke have been described with Magnetic Resonance Imaging (MRI) and perfusion Positron Emission Tomography (PET), but no data on in vivo synaptic changes exist. Recently, imaging of synaptic density became available by targeting synaptic vesicle protein 2 A, a protein ubiquitously expressed in all presynaptic nerve terminals. We hypothesized that in subacute ischemic stroke loss of synaptic density can be evaluated with 11C-UCB-J PET in the ischemic tissue and that alterations in synaptic density can be present in brain regions beyond the ischemic core. We recruited ischemic stroke patients to undergo 11C-UCB-J PET/MR imaging 21 ± 8 days after stroke onset to investigate regional 11C-UCB-J SUVR (standardized uptake value ratio). There was a decrease (but residual signal) of 11C-UCB-J SUVR within the lesion of 16 stroke patients compared to 40 healthy controls (ratiolesion/controls = 0.67 ± 0.28, p = 0.00023). Moreover, 11C-UCB-J SUVR was lower in the non-lesioned tissue of the affected hemisphere compared to the unaffected hemisphere (ΔSUVR = −0.17, p = 0.0035). The contralesional cerebellar hemisphere showed a lower 11C-UCB-J SUVR compared to the ipsilesional cerebellar hemisphere (ΔSUVR = −0.14, p = 0.0048). In 8 out of 16 patients, the asymmetry index suggested crossed cerebellar diaschisis. Future research is required to longitudinally study these changes in synaptic density and their association with outcome.

scholarly journals Nuclear medicine imaging technique in the erectile dysfunction evaluation: a mini-review

2007 ◽  
Vol 50 (spe) ◽  
pp. 91-96 ◽  
Author(s):  
Camila Godinho Ribeiro ◽  
Regina Moura ◽  
Rosane de Figueiredo Neves ◽  
Jean Pierre Spinosa ◽  
Mario Bernardo-Filho
Keyword(s):  
Nuclear Medicine ◽  
Erectile Dysfunction ◽  
Sexual Arousal ◽  
Single Photon ◽  
Photon Emission ◽  
Brain Regions ◽  
Emission Computed Tomography ◽  
Nuclear Medicine Imaging ◽  
Positron Emission

Functional imaging with positron emission tomography and single photon emission computed tomography is capable of visualizing subtle changes in physiological function in vivo. Erectile dysfunction(ED) diminishes quality of life for affected men and their partners. Identification of neural substrates may provide information regarding the pathophysiology of types of sexual dysfunction originating in the brain. The aim of this work is to verify the approaches of the nuclear medicine techniques in the evaluation of the erectile function/disfunction. A search using the words ED and nuclear medicine, ED and scintigraphy, ED and spect and ED and pet was done in the PubMed. The number of citations in each subject was determined. Neuroimaging techniques offer insight into brain regions involved in sexual arousal and inhibition. To tackle problems such as hyposexual disorders or ED caused by brain disorders, it is crucial to understand how the human brain controls sexual arousal and penile erection.

scholarly journals In vivo evidence for dysregulation of mGluR5 as a biomarker of suicidal ideation

2019 ◽  
Vol 116 (23) ◽  
pp. 11490-11495 ◽  
Author(s):  
Margaret T. Davis ◽  
Ansel Hillmer ◽  
Sophie E. Holmes ◽  
Robert H. Pietrzak ◽  
Nicole DellaGioia ◽  
...  
Keyword(s):  
Suicidal Ideation ◽  
Suicide Risk ◽  
Potential Role ◽  
Input Function ◽  
Brain Regions ◽  
Volume Of Distribution ◽  
Regions Of Interest ◽  
Emission Tomography ◽  
Positron Emission

Recent evidence implicates dysregulation of metabotropic glutamatergic receptor 5 (mGluR5) in pathophysiology of PTSD and suicidality. Using positron emission tomography and [18F]FPEB, we quantified mGluR5 availability in vivo in individuals with PTSD (n = 29) and MDD (n = 29) as a function of suicidal ideation (SI) to compare with that of healthy comparison controls (HC; n = 29). Volume of distribution was computed using a venous input function in the five key frontal and limbic brain regions. We observed significantly higher mGluR5 availability in PTSD compared with HC individuals in all regions of interest (P’s = 0.001–0.01) and compared with MDD individuals in three regions (P’s = 0.007). mGluR5 availability was not significantly different between MDD and HC individuals (P = 0.17). Importantly, we observed an up-regulation in mGluR5 availability in the PTSD-SI group (P’s = 0.001–0.007) compared with PTSD individuals without SI. Findings point to the potential role for mGluR5 as a target for intervention and, potentially, suicide risk management in PTSD.

scholarly journals Measurement of Blood—Brain Barrier Permeability with Positron Emission Tomography and [68Ga]EDTA

1984 ◽  
Vol 4 (3) ◽  
pp. 323-328 ◽  
Author(s):  
R. M. Kessler ◽  
J. C. Goble ◽  
J. H. Bird ◽  
M. E. Girton ◽  
J. L. Doppman ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Blood Brain Barrier ◽  
Quantitative Measure ◽  
Brain Regions ◽  
Emission Tomography ◽  
Brain Barrier ◽  
Blood Brain ◽  
Positron Emission ◽  
Area Product

Positron emission tomography (PET) was employed to examine time-dependent changes in blood–brain barrier (BBB) permeability to [68Ga]ethylenediaminetetraacetate (EDTA) in the rhesus monkey, following reversible barrier opening by intracarotid infusion of a hypertonic mannitol solution. The PET technique, when combined with measurements of plasma radioactivity, provided a quantitative measure of the cerebrovascular permeability-area product ( PA) at different times following mannitol infusion. Hypertonic mannitol treatment reversibly increased PA to [68Ga]EDTA more than 10-fold; much of the barrier effect was over by 10 min after mannitol treatment. The results show that PET can be used to measure transient changes in BBB integrity in specific brain regions, under in vivo, noninvasive conditions.

scholarly journals Influence of nicotine upon human brain metabolism, an in vivo noninvasive Near Infrared Spectroscopy (NIRS) study

2021 ◽  
Vol 4 (4) ◽  
pp. 01-07
Author(s):  
Francesco Crespi
Keyword(s):  
Infrared Spectroscopy ◽  
Near Infrared Spectroscopy ◽  
Brain Metabolism ◽  
Near Infrared ◽  
Brain Regions ◽  
Positive Influence ◽  
Total Blood ◽  
Nicotine Administration ◽  
Positron Emission

Nicotine, a natural alkaloid derived from tobacco, is involved in various outcomes ranging from addiction to toxicity and/or neuro-protective actions. Nevertheless, the literature on the effects of nicotine administration upon the activity of brain regions is mixed; either increased, decreased, or no overall effect was reported when being evaluated by various methodologies such as positron emission tomography (PET), functional Magnetic Resonance Imaging (fMRI). In this work, Near Infrared Spectroscopy (NIRS) is applied as it allows monitoring oxygen saturation in the living tissue as well as changes in oxygenation of hemoglobin and when applied on brain studies, it gives indications of cerebral haemo-dynamics as well as brain metabolism. In particular, here NIRS has been applied in human volunteers as this methodology is based upon the use of harmless radiations so that to provide a non-invasive, non-ionizing procedure to monitor 2 main forms of hae­moglobin: oxy-haemoglobin (HbO2) and deoxy-haemoglobin (Hb). The data gathered indicate an overall positive influence of nicotine upon HbO2 levels, as well as total blood volume (V) therefore suggesting an increased brain metabolism. Finally these data further propose NIRS with its characteristics of noninvasiveness, easy to-use, portable, restraint-free therefore relatively psychologically undemanding, as replicable and ideal methodology for clinical applications and translational approaches.

scholarly journals Endogenous μ-opioid receptor system modulates sex drive in human males

2021 ◽  
Author(s):  
Lauri Nummenmaa ◽  
Patrick Jern ◽  
Tuulia Malén ◽  
Tatu Kantonen ◽  
Laura Pekkarinen ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Hierarchical Regression ◽  
Receptor System ◽  
Bayesian Hierarchical ◽  
Midcingulate Cortex ◽  
Positron Emission ◽  
Sex Drive ◽  
Cortical Density ◽  
Morphometry Analysis

AbstractThe endogenous mu-opioid receptor (MOR) system modulates a multitude of social and reward-related functions, and exogenous opiates also influence sex drive in humans and animals. However, there is no in vivo evidence for the contribution of MOR system on human sex drive. Here we measured healthy male subjects’ (n=52) brain’s MOR availability with positron emission tomography (PET) using an agonist radioligand, [11C]carfentanil, that has high affinity for MORs. Sex drive was measured using self-reports of engaging in sexual behaviour (sex with partner and masturbating). Bayesian hierarchical regression analysis revealed that sex drive was positively associated with MOR availability in cortical and subcortical areas, notably in caudate nucleus, hippocampus, and cingulate cortices. These results were replicated in full-volume GLM analysis. Complementary voxel-based morphometry analysis (n=108) provided limited evidence for association between sex drive and cortical density in the midcingulate cortex. We conclude that MOR system modulates individual differences in sex drive in human males.

Abstract T MP46: Stroke-Related Neuroplasticity During Steering of Human Gait

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Caroline Paquette ◽  
Jean-Paul Soucy
Keyword(s):  
Brain Plasticity ◽  
Brain Activity ◽  
Brain Regions ◽  
Whole Body ◽  
Human Gait ◽  
Stroke Survivors ◽  
Post Stroke ◽  
Positron Emission ◽  
18F Fdg

Background: The risk of falling is higher in stroke survivors than among the general population. These falls are more frequent during walking and transfers or during turning. The neuronal substrates involved in steering of locomotion are poorly understood due to methodological limitations in quantifying brain activations during whole-body movements. Thus, no data is currently available to study the mechanisms of post-stroke brain plasticity for steering of gait. This study tested the hypothesis that stroke-induced neuroplastic changes for steering of gait can be quantified using 18F- fluorodesoxy-glucose (18F-FDG) Positron Emission Tomography (PET) in-vivo in humans Methods: PET imaging with 18F-FDG tracer was used to quantify cerebral glucose metabolism (CMRGlc) during two locomotor tasks (straight walking and turning) measured on separate days. Immediately prior to each walking task, a 5 mCi bolus of 18F-FDG was injected. Subjects walked for 40 minutes (duration of 18F-FDG uptake). Subjects were scanned on an ECAT HR+ scan (20min emission followed by 10min transmission) within 10 minutes of completing the walking task, well within reaching the 2h half-life of 18F. Images obtained during straight walking were subtracted from the ones acquired during steering Results: Subjects post-stroke showed an asymmetrical pattern of CMRGlc in sensorimotor areas and superior parietal lobule where the affected hemisphere shows no increase in CMRGlc. Differences between groups were also observed in the cerebellum where CMRGlc was increased in the vermis for controls, an area predominant for the control of trunk and gait. Stroke subjects, in contrast, showed increased CMRGlc in the hemishperes, associated with goal-directed leg movements. Conclusions: Neuroplasticity in complex locomotor tasks such as steering can be quantified using 18F-FDG PET in subjects post-stroke. This study showed that changes affect several brain regions remote to the infarct. Understanding stroke-related changes in brain activity during steering of locomotion is crucial for improving rehabilitative strategies to minimize falls and injuries in stroke survivors.

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