scholarly journals Characterisation of the Contribution of the GABA-Benzodiazepine α1 Receptor Subtype to [11C]Ro15-4513 PET Images

2012 ◽  
Vol 32 (4) ◽  
pp. 731-744 ◽  
Author(s):  
James FM Myers ◽  
Lula Rosso ◽  
Ben J Watson ◽  
Sue J Wilson ◽  
Nicola J Kalk ◽  
...  
Keyword(s):  
Spectral Analysis ◽  
A Priori ◽  
Benzodiazepine Receptor ◽  
Brain Regions ◽  
Complex Model ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Time Activity ◽  
Positron Emission ◽  
The Impact

This positron emission tomography (PET) study aimed to further define selectivity of [11C]Ro15-4513 binding to the GABARα5 relative to the GABARα1 benzodiazepine receptor subtype. The impact of zolpidem, a GABARα1-selective agonist, on [11C]Ro15-4513, which shows selectivity for GABARα5, and the nonselective benzodiazepine ligand [11C]flumazenil binding was assessed in humans. Compartmental modelling of the kinetics of [11C]Ro15-4513 time-activity curves was used to describe distribution volume ( VT) differences in regions populated by different GABA receptor subtypes. Those with low α5 were best fitted by one-tissue compartment models; and those with high α5 required a more complex model. The heterogeneity between brain regions suggested spectral analysis as a more appropriate method to quantify binding as it does not a priori specify compartments. Spectral analysis revealed that Zolpidem caused a significant VT decrease (~10%) in [11C]flumazenil, but no decrease in [11C]Ro15-4513 binding. Further analysis of [11C]Ro15-4513 kinetics revealed additional frequency components present in regions containing both α1 and α5 subtypes compared with those containing only α1. Zolpidem reduced one component (mean ± s.d.: 71% ± 41%), presumed to reflect α1-subtype binding, but not another (13% ± 22%), presumed to reflect α5. The proposed method for [11C]Ro15-4513 analysis may allow more accurate selective binding assays and estimation of drug occupancy for other nonselective ligands.

Effects of Citalopram Infusion on the Serotonin Transporter Binding of [11C]DASB in Healthy Controls

2008 ◽  
Vol 28 (8) ◽  
pp. 1478-1490 ◽  
Author(s):  
Rainer Hinz ◽  
Sudhakar Selvaraj ◽  
N Venkatesha Murthy ◽  
Zubin Bhagwagar ◽  
Matthew Taylor ◽  
...  
Keyword(s):  
Spectral Analysis ◽  
Serotonin Transporter ◽  
Area Under The Curve ◽  
Input Function ◽  
Brain Regions ◽  
Time Activity ◽  
Quantitative Studies ◽  
Logan Plot ◽  
Positron Emission ◽  
Arterial Plasma

The positron emission tomography (PET) ligand [11C]DASB is currently the most widely used imaging agent for quantitative studies of the serotonin transporter (SERT) in human brain. The aim of this work was to assess the effects of an intravenous infusion of 10 mg citalopram, a selective serotonin reuptake inhibitor (SSRI), before the PET scan on the kinetics of [11C]DASB in arterial plasma and in selected brain regions. Four healthy male volunteers underwent two PET scans with a mean of 523 MBq injected activity after either placebo or Citalopram infusion in a randomised design. The Citalopram infusion led to a substantial increase of the area under the curve of the metabolite-corrected arterial plasma input function. Total volumes of distribution VT were estimated applying the Logan plot to regional time—activity curves or by generating parametric maps with spectral analysis. A mean reduction of the cerebellar VT of 19% with Logan analysis and of 24% with spectral analysis was observed after Citalopram infusion, which confirms previous findings of displaceable SERT ligand binding in cerebellar grey matter. The SERT occupancy for six target regions with moderate to high binding was 60% derived from BPND and 69% derived from BPP.

scholarly journals Differential Expression of Melatonin Receptor Subtypes MelIa, MelIb and MelIc in Relation to Melatonin Binding in the Male Songbird Brain

2014 ◽  
Vol 85 (1) ◽  
pp. 4-14 ◽  
Author(s):  
Leonida Fusani ◽  
Manfred Gahr
Keyword(s):  
Expression Patterns ◽  
General Pattern ◽  
Passerine Bird ◽  
Brain Regions ◽  
Receptor Expression ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Melatonin Receptor ◽  
Brain Areas ◽  
Specific Expression

Previous autoradiography studies illustrated that several areas of the avian brain can bind the pineal hormone melatonin. In birds, there are three melatonin receptor (MelR) subtypes: MelIa, MelIb and MelIc. To date, their brain distribution has not been studied in any passerine bird. Therefore, we investigated mRNA distribution of MelR subtypes in adjacent sections of the brain of two songbirds, the blackcap and the zebra finch, in parallel with that of 2-[125I]-iodomelatonin (IMEL) binding sites in the same brains. The general pattern of receptor expression shown by in situ hybridization of species-specific probes matched well with that of IMEL binding. However, the expression of the three subtypes was area specific with similar patterns in the two species. Some brain areas expressed only one receptor subtype, most brain regions co-expressed either MelIa with MelIb or MelIa with MelIc, whereas few areas expressed MelIb and MelIc or all three receptor subtypes. Since many sensory areas, most thalamic areas and subareas of the neopallium, a cortex analogue, express MelR, it is likely that most sensory motor integration functions are melatonin sensitive. Further, the area-specific expression patterns suggest that the regulatory role of melatonin differs among different brain areas. Since subareas of well-defined neural circuits, such as the visual system or the song control system, are equipped with different receptor types, we hypothesize a diversity of functions for melatonin in the control of sensory integration and behavior.

scholarly journals Functional neuroimaging of psychiatric disorders: exploring hidden behaviour

2004 ◽  
Vol 34 (4) ◽  
pp. 577-581 ◽  
Author(s):  
P. C. FLETCHER
Keyword(s):  
Functional Neuroimaging ◽  
Brain Activity ◽  
Cognitive Strategies ◽  
Healthy Person ◽  
Brain Regions ◽  
Task Demands ◽  
Unrealistic Expectation ◽  
Positron Emission ◽  
The Impact ◽  
Function Mapping

From the outset, people have had high expectations of functional neuroimaging. Many will have been disappointed. After roughly a decade of widespread use, even an enthusiastic advocate must be diffident about the impact of the two most frequently used techniques – positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) – upon clinical psychiatry. Perhaps this disappointment arises from an unrealistic expectation of what these techniques are able to tell us about the workings of the normal and the disordered brain. Anyone who hoped for intricate and unambiguous region-to-function mapping was always going to be disappointed. This expectation presupposes, among other things, a thorough understanding of the cognitive functions that are to be mapped onto the brain regions. This understanding, however, while developing, is still rudimentary. Mapping disorder along comparable lines is even more complex since it demands two levels of understanding. The first is of the healthy region-to-function mapping, the second of the disordered region-to-function mapping, which immediately demands a consideration of the nature of the function in the disordered state. After all, someone with schizophrenia, when confronted with a psychological task, might tackle it in a very different way, in terms of the cognitive strategies used, from a healthy person confronted with the same task. The observation that brain activity differs across the two individuals would only be interpretable insofar as one thoroughly understood the processes that each individual invoked in response to the task demands.

scholarly journals Measurement of Benzodiazepine Receptor Number and Affinity in Humans Using Tracer Kinetic Modeling, Positron Emission Tomography, and [11C]Flumazenil

1993 ◽  
Vol 13 (4) ◽  
pp. 656-667 ◽  
Author(s):  
Julie C. Price ◽  
Helen S. Mayberg ◽  
Robert F. Dannals ◽  
Alan A. Wilson ◽  
Hayden T. Ravert ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Specific Activity ◽  
Free Fraction ◽  
Benzodiazepine Receptor ◽  
Occipital Cortex ◽  
Compartment Model ◽  
Brain Regions ◽  
Emission Tomography ◽  
Positron Emission ◽  
Convergence Problems

Kinetic methods were used to obtain regional estimates of benzodiazepine receptor concentration ( Bmax) and equilibrium dissociation constant ( Kd) from high and low specific activity (SA) [11C]flumazenil ([11C] Ro 15-1788) positron emission tomography studies of five normal volunteers. The high and low SA data were simultaneously fit to linear and nonlinear three-compartment models, respectively. An additional inhibition study (pretreatment with 0.15 mg/kg of flumazenil) was performed on one of the volunteers, which resulted in an average gray matter K1/ k2 estimate of 0.68 ± 0.08 ml/ml (linear three-compartment model, nine brain regions). The free fraction of flumazenil in plasma ( f1) was determined for each study (high SA f1: 0.50 ± 0.03; low SA f1: 0.48 ± 0.05). The free fraction in brain ( f2) was calculated using the inhibition K1/ k2 ratio and each volunteer's mean f1 value ( f2 across volunteers = 0.72 ± 0.03 ml/ml). Three methods (Methods I–III) were examined. Method I determined five kinetic parameters simultaneously [ K1, k2, k3 (= kon f2 Bmax), k4, and kon f2/SA] with no a priori constraints. An average kon value of 0.030 ± 0.003 n M−1 min−1 was estimated for receptor-rich regions using Method I. In Methods II and III, the kon f2/SA parameter was specifically constrained using the Method I value of kon and the volunteer's values of f2 and low SA (Ci/μmol). Four parameters were determined simultaneously using Method II. In Method III, K1/ k2 was fixed to the inhibition value and only three parameters were estimated. Method I provided the most variable results and convergence problems for regions with low receptor binding. Method II provided results that were less variable but very similar to the Method I results, without convergence problems. However, the K1/ k2 ratios obtained by Method II ranged from 1.07 in the occipital cortex to 0.61 in the thalamus. Fixing the K1/ k2 ratio in Method III provided a method that was physiologically consistent with the fixed value of f2 and resulted in parameters with considerably lower variability. The average Bmax values obtained using Method III were 100 ± 25 n M in the occipital cortex, 64 ±18 n M in the cerebellum, and 38 ± 5.5 n M in the thalamus; the average Kd was 8.9 ± 1.0 n M (five brain regions).

Aliskiren, exendin-4, and insulin: their impact on endothelin receptor subtype(s) regulation/binding in type 1 diabetic rat hearts

2013 ◽  
Vol 91 (10) ◽  
pp. 830-838 ◽  
Author(s):  
Sawsan M. Al Lafi ◽  
Shushan B. Artinian ◽  
Suzan S. Boutary ◽  
Nadine S. Zwainy ◽  
Khalil M. Bitar ◽  
...  
Keyword(s):  
Binding Affinity ◽  
Diabetic Rat ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Rat Hearts ◽  
Heart Perfusion ◽  
Glucagon Like Peptide 1 ◽  
Coronary Endothelium ◽  
The Impact

This study focuses on the impact of aliskiren and (or) glucagon-like peptide-1 analogue on the binding affinity/regulation of endothelin-1 (ET-1) to its receptor subtypes A (ETAR) and B (ETBR) at the level of the coronary endothelium and the cardiomyocytes in a type-1 diabetic rat model. Seven groups were used: (i) normal rats, (ii) rats with induced diabetes, (iii) rats with induced diabetes that were treated with insulin, (iv) rats with induced diabetes that were treated with exendin-4, (v) rats with induced diabetes that were treated with aliskiren, (vi) rats with induced diabetes that were co-treated with insulin plus aliskiren, and (vii) rats with induced diabetes that were co-treated with exendin-4 plus aliskiren. Heart perfusion with [125I]-ET-1 was employed to estimate ET-1 binding affinity (τ = 1/K–n) to ETAR and ETBR at the level of the coronary endothelium and the cardiomyocytes. Plasma ET-1 levels were measured using enzyme immunoassay, whereas densities of ETAR and ETBR were detected using Western blot. No significance differences were detected in the τ of ETAR and ETBR between normal and diabetic in cardiomyocytes and the coronary endothelium. Exendin-4 normalized the τ value for ETAR and ETBR on coronary endothelium, while aliskiren normalized it on cardiomyocytes. Furthermore, ETAR and ETBR densities were normalized with monotreatments of aliskiren and exendin-4, compared with up-regulated ETAR and down-regulated ETBR band densities in the diabetic animals. Our data indicate that aliskiren alleviates diabetes-associated hypertrophy in type 1 diabetes mellitus.

scholarly journals Inverse relationship between brain glucose and ketone metabolism in adults during short-term moderate dietary ketosis: A dual tracer quantitative positron emission tomography study

2016 ◽  
Vol 37 (7) ◽  
pp. 2485-2493 ◽  
Author(s):  
Alexandre Courchesne-Loyer ◽  
Etienne Croteau ◽  
Christian-Alexandre Castellano ◽  
Valérie St-Pierre ◽  
Marie Hennebelle ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Brain Regions ◽  
Healthy Adults ◽  
Emission Tomography ◽  
Energy Requirements ◽  
Brain Glucose ◽  
Positron Emission ◽  
Before And After ◽  
The Impact ◽  
Brain Energy

Ketones (principally β-hydroxybutyrate and acetoacetate (AcAc)) are an important alternative fuel to glucose for the human brain, but their utilisation by the brain remains poorly understood. Our objective was to use positron emission tomography (PET) to assess the impact of diet-induced moderate ketosis on cerebral metabolic rate of acetoacetate (CMRa) and glucose (CMRglc) in healthy adults. Ten participants (35 ± 15 y) received a very high fat ketogenic diet (KD) (4.5:1; lipid:protein plus carbohydrates) for four days. CMRa and CMRglc were quantified by PET before and after the KD with the tracers, 11C-AcAc and 18F-fluorodeoxyglucose (18F-FDG), respectively. During the KD, plasma ketones increased 8-fold ( p = 0.005) while plasma glucose decreased by 24% ( p = 0.005). CMRa increased 6-fold ( p = 0.005), whereas CMRglc decreased by 20% ( p = 0.014) on the KD. Plasma ketones were positively correlated with CMRa (r = 0.93; p < 0.0001). After four days on the KD, CMRa represented 17% of whole brain energy requirements in healthy adults with a 2-fold difference across brain regions (12–24%). The CMR of ketones (AcAc and β-hydroxybutyrate combined) while on the KD was estimated to represent about 33% of brain energy requirements or approximately double the CMRa. Whether increased ketone availability raises CMR of ketones to the same extent in older people as observed here or in conditions in which chronic brain glucose hypometabolism is present remains to be determined.

scholarly journals Effects of Carbidopa Premedication on 18F-FDOPA PET Imaging of Glioma: A Multiparametric Analysis

Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5340
Author(s):  
Marie Bros ◽  
Timothée Zaragori ◽  
Fabien Rech ◽  
Marie Blonski ◽  
Gabriela Hossu ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Independent Predictor ◽  
Simulated Data ◽  
Brain Regions ◽  
Dynamic Parameters ◽  
Newly Diagnosed ◽  
Time Activity ◽  
Multicentric Study ◽  
Absolute Correlation ◽  
The Impact

Purpose: This study aimed to determine the impact of carbidopa premedication on static, dynamic and radiomics parameters of 18F-FDOPA PET in brain tumors. Methods: The study included 54 patients, 18 of whom received carbidopa, who underwent 18F-FDOPA PET for newly diagnosed gliomas. SUV-derived, 105 radiomics features and TTP dynamic parameters were extracted from volumes of interest in healthy brains and tumors. Simulation of the effects of carbidopa on time-activity curves were generated. Results: All static and TTP dynamic parameters were significantly higher in healthy brain regions of premedicated patients (ΔSUVmean = +53%, ΔTTP = +48%, p < 0.001). Furthermore, carbidopa impacted 81% of radiomics features, of which 92% correlated with SUVmean (absolute correlation coefficient ≥ 0.4). In tumors, premedication with carbidopa was an independent predictor of SUVmean (ΔSUVmean = +52%, p < 0.001) and TTP (ΔTTP = +24%, p = 0.025). All parameters were no longer significantly modified by carbidopa premedication when using ratios to healthy brain. Simulated data confirmed that carbidopa leads to higher tumor TTP values, corrected by the ratios. Conclusion: In 18F-FDOPA PET, carbidopa induces similarly higher SUV and TTP dynamic parameters and similarly impacts SUV-dependent radiomics in healthy brain and tumor regions, which is compensated for by correcting for the tumor-to-healthy-brain ratio. This is a significant advantage for multicentric study harmonization.

scholarly journals Spatial patterns in functional brain connectomes reflect acute and chronic cannabis use

2021 ◽  
Author(s):  
JG Ramaekers ◽  
NL Mason ◽  
SW Toennes ◽  
EL Theunissen ◽  
E Amico
Keyword(s):  
Spatial Patterns ◽  
Resting State ◽  
A Priori ◽  
Brain Regions ◽  
Brain Network ◽  
Cannabis Use ◽  
Connectivity Pattern ◽  
Functional Brain ◽  
Acute And Chronic Exposure ◽  
The Impact

AbstractResting state fMRI has been employed to identify alterations in functional connectivity within or between brain regions following acute and chronic exposure to Δ9-tetrahydrocannabinol (THC), the psychoactive component in cannabis. Most studies focused a priori on a limited number of local brain areas or circuits, without considering the impact of cannabis on wholebrain network organization. The present study attempted to identify changes in the wholebrain human functional connectome as assessed with ultra-high field (7T) resting state scans of occasional (N=12) and chronic cannabis users (N=14) during placebo and following vaporization of cannabis. Two distinct data-driven methodologies, i.e. network-based statistics (NBS) and connICA, were used to identify changes in functional connectomes associated with acute cannabis intoxication and chronic cannabis use. Both methodologies revealed a broad state of hyperconnectivity within the entire range of major brain networks in chronic cannabis users compared to occasional cannabis users, which might be reflective of an adaptive network reorganization following prolonged cannabis exposure. The connICA methodology also extracted a distinct spatial connectivity pattern of hypoconnectivity involving the dorsal attention, limbic, subcortical and cerebellum networks and of hyperconnectivity between the default mode and ventral attention network, that was associated with the feeling of subjective high during THC intoxication across both user groups. Whole-brain network approaches identified spatial patterns in functional brain connectomes that distinguished acute from chronic cannabis use, and offer an important utility for probing the interplay between short and long-term alterations in functional brain dynamics when progressing from occasional to chronic use of cannabis.

scholarly journals The Role of Adenosine A2AReceptor, CYP450s, and PPARs in the Regulation of Vascular Tone

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Maan T. Khayat ◽  
Mohammed A. Nayeem
Keyword(s):  
Vascular Endothelium ◽  
Adenosine Receptors ◽  
Vascular Tone ◽  
Continuous Process ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptors ◽  
The Impact

Adenosine is an endogenous mediator involved in a myriad of physiologic functions, including vascular tone regulation. It is also implicated in some pathologic conditions. Four distinct receptor subtypes mediate the effects of adenosine, such as its role in the regulation of the vascular tone. Vascular tone regulation is a complex and continuous process which involves many mechanisms and mediators that are not fully disclosed. The vascular endothelium plays a pivotal role in regulating blood flow to and from all body organs. Also, the vascular endothelium is not merely a physical barrier; it is a complex tissue with numerous functions. Among adenosine receptors,A2Areceptor subtype (A2AAR) stands out as the primary receptor responsible for the vasodilatory effects of adenosine. This review focuses on important effectors of the vascular endothelium, including adenosine, adenosine receptors, EETs (epoxyeicosatrienoic acids), HETEs (hydroxyeicosatetraenoic acids), PPARs (peroxisome proliferator-activated receptors), andKATPchannels. Given the impact of vascular tone regulation in cardiovascular physiology and pathophysiology, better understanding of the mechanisms affecting it could have a significant potential for developing therapeutic agents for cardiovascular diseases.

scholarly journals The Pandemic Brain: neuroinflammation in healthy, non-infected individuals during the COVID-19 pandemic

2021 ◽  
Author(s):  
Ludovica Brusaferri ◽  
Zeynab Alshelh ◽  
Daniel Martins ◽  
Minhae Kim ◽  
Akila Weerasekera ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Human Brain ◽  
Constitutive Expression ◽  
Symptom Burden ◽  
Brain Regions ◽  
Translocator Protein ◽  
Brain Atlas ◽  
Resonance Spectroscopy ◽  
Positron Emission ◽  
The Impact

The impact of COVID-19 on human health extends beyond the morbidity and death toll directly caused by the SARS-CoV-2 virus. In fact, accumulating evidence indicates a global increase in the incidence of fatigue, brain fog and depression, including among non-infected, since the pandemic onset. Motivated by previous evidence linking those symptoms to neuroimmune activation in other pathological contexts, we hypothesized that subjects examined after the enforcement of lockdown/stay-at-home measures would demonstrate increased neuroinflammation. We performed simultaneous brain Positron Emission Tomography / Magnetic Resonance Imaging in healthy volunteers either before (n=57) or after (n=15) the 2020 Massachusetts lockdown, using [11C]PBR28, a radioligand for the glial marker 18 kDa translocator protein (TSPO). First, we compared [11C]PBR28 signal across pre- and post-lockdown cohorts. Then, we evaluated the link between neuroinflammatory signals and scores on a questionnaire assessing mental and physical impacts of the pandemic. Further, we investigated multivariate associations between the spatial pattern of [11C]PBR28 post-lockdown changes and constitutive brain gene expression in post-mortem brains (Allen Human Brain Atlas). Finally, in a subset (n=13 pre-lockdown; n=11 post-lockdown), we also used magnetic resonance spectroscopy to quantify brain (thalamic) levels of myoinositol (mIns), another neuroinflammatory marker. Both [11C]PBR28 and mIns signals were overall stable pre-lockdown, but markedly elevated after lockdown, including within brain regions previously implicated in stress, depression and 'sickness behaviors'. Moreover, amongst the post-lockdown cohort, subjects endorsing higher symptom burden showed higher [11C]PBR28 PET signal compared to those reporting little/no symptoms. Finally, the post-lockdown [11C]PBR28 signal changes were spatially aligned with the constitutive expression of several genes highly expressed in glial/immune cells and/or involved in neuroimmune signaling. Our results suggest that pandemic-related stressors may have induced sterile neuroinflammation in healthy individuals that were not infected with SARS-CoV-2. This work highlights the possible impact of the COVID-19 pandemic-related lifestyle disruptions on human brain health.

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