scholarly journals Obesity risk is associated with altered cerebral glucose metabolism and decreased μ-opioid and CB1 receptor availability

2021 ◽  
Author(s):  
Tatu Kantonen ◽  
Laura Pekkarinen ◽  
Tomi Karjalainen ◽  
Marco Bucci ◽  
Kari Kalliokoski ◽  
...  
Keyword(s):  
Risk Factors ◽  
Glucose Uptake ◽  
Familial Risk ◽  
Health Concern ◽  
Obesity Risk ◽  
Brain Glucose ◽  
Positron Emission ◽  
The Central Nervous System ◽  
Familial Obesity ◽  
The Brain

Abstract Background Obesity is a pressing public health concern worldwide. Novel pharmacological means are urgently needed to combat the increase of obesity and accompanying type 2 diabetes (T2D). Although fully established obesity is associated with neuromolecular alterations and insulin resistance in the brain, potential obesity-promoting mechanisms in the central nervous system have remained elusive. In this triple-tracer positron emission tomography study, we investigated whether brain insulin signaling, μ-opioid receptors (MORs) and cannabinoid CB1 receptors (CB1Rs) are associated with risk for developing obesity. Methods Subjects were 41 young non-obese males with variable obesity risk profiles. Obesity risk was assessed by subjects’ physical exercise habits, body mass index and familial risk factors, including parental obesity and T2D. Brain glucose uptake was quantified with [18F]FDG during hyperinsulinemic euglycemic clamp, MORs were quantified with [11C]carfentanil and CB1Rs with [18F]FMPEP-d2. Results Subjects with higher obesity risk had globally increased insulin-stimulated brain glucose uptake (19 high-risk subjects versus 19 low-risk subjects), and familial obesity risk factors were associated with increased brain glucose uptake (38 subjects) but decreased availability of MORs (41 subjects) and CB1Rs (36 subjects). Conclusions These results suggest that the hereditary mechanisms promoting obesity may be partly mediated via insulin, opioid and endocannabinoid messaging systems in the brain.

scholarly journals The Obesity Risk SNP (rs17782313) near the MC4R Gene Is Not Associated with Brain Glucose Uptake during Insulin Clamp—A Study in Finns

2021 ◽  
Vol 10 (6) ◽  
pp. 1312
Author(s):  
Eleni Rebelos ◽  
Miikka-Juhani Honka ◽  
Laura Ekblad ◽  
Marco Bucci ◽  
Jarna C. Hannukainen ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Statistical Parametric Mapping ◽  
Obesity Risk ◽  
Melanocortin System ◽  
Single Nucleotide ◽  
Brain Glucose ◽  
Mc4r Gene ◽  
Insulin Clamp ◽  
Positron Emission ◽  
Fractional Uptake

The melanocortin system is involved in the control of adiposity through modulation of food intake and energy expenditure. The single nucleotide polymorphism (SNP) rs17782313 near the MC4R gene has been linked to obesity, and a previous study using magnetoencephalography has shown that carriers of the mutant allele have decreased cerebrocortical response to insulin. Thus, in this study, we addressed whether rs17782313 associates with brain glucose uptake (BGU). Here, [18F]-fluorodeoxyglucose positron emission tomography (PET) data from 113 Finnish subjects scanned under insulin clamp conditions who also had the rs17782313 determined were compiled from a single-center cohort. BGU was quantified by the fractional uptake rate. Statistical analysis was performed with statistical parametric mapping. There was no difference in age, BMI, and insulin sensitivity as indexed by the M value between the rs17782313-C allele carriers and non-carriers. Brain glucose uptake during insulin clamp was not different by gene allele, and it correlated with the M value, in both the rs17782313-C allele carriers and non-carriers. The obesity risk SNP rs17782313 near the MC4R gene is not associated with brain glucose uptake during insulin clamp in humans, and this frequent mutation cannot explain the enhanced brain glucose metabolic rates in insulin resistance.

scholarly journals 27-Hydroxycholesterol impairs neuronal glucose uptake through an IRAP/GLUT4 system dysregulation

2017 ◽  
Vol 214 (3) ◽  
pp. 699-717 ◽  
Author(s):  
Muhammad-Al-Mustafa Ismail ◽  
Laura Mateos ◽  
Silvia Maioli ◽  
Paula Merino-Serrais ◽  
Zeina Ali ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Renin Angiotensin System ◽  
Angiotensin Iv ◽  
Memory Decline ◽  
Brain Glucose ◽  
Glut4 Expression ◽  
Altered Glucose ◽  
X Receptors ◽  
The Brain

Hypercholesterolemia is associated with cognitively deteriorated states. Here, we show that excess 27-hydroxycholesterol (27-OH), a cholesterol metabolite passing from the circulation into the brain, reduced in vivo brain glucose uptake, GLUT4 expression, and spatial memory. Furthermore, patients exhibiting higher 27-OH levels had reduced 18F-fluorodeoxyglucose uptake. This interplay between 27-OH and glucose uptake revealed the engagement of the insulin-regulated aminopeptidase (IRAP). 27-OH increased the levels and activity of IRAP, countered the IRAP antagonist angiotensin IV (AngIV)–mediated glucose uptake, and enhanced the levels of the AngIV-degrading enzyme aminopeptidase N (AP-N). These effects were mediated by liver X receptors. Our results reveal a molecular link between cholesterol, brain glucose, and the brain renin-angiotensin system, all of which are affected in some neurodegenerative diseases. Thus, reducing 27-OH levels or inhibiting AP-N maybe a useful strategy in the prevention of the altered glucose metabolism and memory decline in these disorders.

scholarly journals Multiple nocardial abscesses of the brainstem and spinal cord diagnosed after an open biopsy through a cervical partial central corpectomy: case report

2015 ◽  
Vol 23 (3) ◽  
pp. 290-293 ◽  
Author(s):  
Ian Peeters ◽  
Jan W. Casselman ◽  
Stefaan J. Vandecasteele ◽  
Alexander Janssen ◽  
Bart Regaert ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Cervical Spinal Cord ◽  
Emission Tomography ◽  
Open Biopsy ◽  
Difficult Diagnosis ◽  
Positron Emission ◽  
The Central Nervous System ◽  
Walking Difficulty ◽  
Brain And Spinal Cord ◽  
The Brain

Nocardiosis of the central nervous system is a challenging and difficult diagnosis for the clinician. The combination of infections of the brain and spinal cord is even more rare. The authors report on a patient with multiple lesions in the brainstem and cervical spinal cord. This 81-year-old immunocompetent woman presented with symptoms of progressive walking difficulty and ataxia. The results of an extensive workup with laboratory investigation, MRI, lumbar puncture, positron emission tomography (PET), and bone marrow biopsy remained inconclusive. Only after an open biopsy of a cervical lesion by an anterior approach through a partial central corpectomy of the cervical spine, was the diagnosis of nocardiosis made, allowing for specific antibiotic treatment.

scholarly journals Purinergic Receptors of the Central Nervous System: Biology, PET Ligands, and Their Applications

2020 ◽  
Vol 19 ◽  
pp. 153601212092760
Author(s):  
Hamideh Zarrinmayeh ◽  
Paul R. Territo
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Purinergic Receptors ◽  
P2y Receptors ◽  
Cns Disorders ◽  
Extracellular Adenosine ◽  
Functional Roles ◽  
Positron Emission ◽  
The Central Nervous System ◽  
The Brain

Purinergic receptors play important roles in central nervous system (CNS). These receptors are involved in cellular neuroinflammatory responses that regulate functions of neurons, microglial and astrocytes. Based on their endogenous ligands, purinergic receptors are classified into P1 or adenosine, P2X and P2Y receptors. During brain injury or under pathological conditions, rapid diffusion of extracellular adenosine triphosphate (ATP) or uridine triphosphate (UTP) from the damaged cells, promote microglial activation that result in the changes in expression of several of these receptors in the brain. Imaging of the purinergic receptors with selective Positron Emission Tomography (PET) radioligands has advanced our understanding of the functional roles of some of these receptors in healthy and diseased brains. In this review, we have accumulated a list of currently available PET radioligands of the purinergic receptors that are used to elucidate the receptor functions and participations in CNS disorders. We have also reviewed receptors lacking radiotracer, laying the foundation for future discoveries of novel PET radioligands to reveal these receptors roles in CNS disorders.

scholarly journals Biomarkers for Alzheimer’s Disease Early Diagnosis

2020 ◽  
Vol 10 (3) ◽  
pp. 114 ◽  
Author(s):  
Eva Ausó ◽  
Violeta Gómez-Vicente ◽  
Gema Esquiva
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neuronal Loss ◽  
Diagnostic Tools ◽  
Csf Biomarkers ◽  
Diagnosis And Prognosis ◽  
Positron Emission ◽  
The Central Nervous System ◽  
Magnetic Resonance Imaging Mri ◽  
The Brain

Alzheimer’s disease (AD) is the most common cause of dementia, affecting the central nervous system (CNS) through the accumulation of intraneuronal neurofibrillary tau tangles (NFTs) and β-amyloid plaques. By the time AD is clinically diagnosed, neuronal loss has already occurred in many brain and retinal regions. Therefore, the availability of early and reliable diagnosis markers of the disease would allow its detection and taking preventive measures to avoid neuronal loss. Current diagnostic tools in the brain, such as magnetic resonance imaging (MRI), positron emission tomography (PET) imaging, and cerebrospinal fluid (CSF) biomarkers (Aβ and tau) detection are invasive and expensive. Brain-secreted extracellular vesicles (BEVs) isolated from peripheral blood have emerged as novel strategies in the study of AD, with enormous potential as a diagnostic evaluation of therapeutics and treatment tools. In addition; similar mechanisms of neurodegeneration have been demonstrated in the brain and the eyes of AD patients. Since the eyes are more accessible than the brain, several eye tests that detect cellular and vascular changes in the retina have also been proposed as potential screening biomarkers. The aim of this study is to summarize and discuss several potential markers in the brain, eye, blood, and other accessible biofluids like saliva and urine, and correlate them with earlier diagnosis and prognosis to identify individuals with mild symptoms prior to dementia.

scholarly journals Central GLP-1 contributes to improved cognitive function and brain glucose uptake after duodenum-jejunum bypass on obese and diabetic rats

2021 ◽  
Author(s):  
Rexiati Ruze ◽  
Qian Xu ◽  
Guoqin Liu ◽  
Yuekai Li ◽  
Weijie Chen ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Glucose Uptake ◽  
Diabetic Rats ◽  
Brain Glucose ◽  
Positron Emission ◽  
Myosin Va ◽  
Glucagon Like Peptide 1 ◽  
Underlying Mechanisms ◽  
Related Proteins

The improvement of cognitive function following bariatric surgery has been highlighted, yet its underlying mechanisms remain elusive. Finding the improved brain glucose uptake of patients after Roux-en-Y gastric bypass (RYGB), duodenum-jejunum bypass (DJB) and sham surgery (Sham) were performed on obese and diabetic Wistar rats, and intracerebroventricular (ICV) injection of glucagon-like peptide-1 (GLP-1) analog liraglutide (Lira), antagonist exendin-(9-39) (Exe-9), and the viral-mediated GLP-1 receptor (Glp-1r) knockdown (KD) were applied on both groups to elucidate the role of GLP-1 in mediating cognitive function and brain glucose uptake assessed with the Morris water maze (MWM) and positron emission tomography (PET). Insulin and GLP-1 in serum and cerebral spinal fluid (CSF) were measured, and the expression of glucose uptake-related proteins including GLUT-1, GLUTT-4, pAS160, AS160, Rab10, Myosin-Va as well as the c-fos marker in the brain were examined. Along with augmented glucose homeostasis following DJB, central GLP-1 was correlated with the improved cognitive function and ameliorated brain glucose uptake, which was further confirmed by the enhancive role of Lira on both groups while the Exe-9 and Glp-1r KD were opposite. Known to activate insulin signaling pathways, central GLP-1 contributes to improved cognitive function and brain glucose uptake after DJB.

scholarly journals Reduction of Amyloid in the Brain and Retina After Treatment With IVIG for Mild Cognitive Impairment

2020 ◽  
Vol 35 ◽  
pp. 153331751989980 ◽  
Author(s):  
Shawn Kile ◽  
William Au ◽  
Carol Parise ◽  
Jaideep Sohi ◽  
Tracy Yarbrough ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Standard Uptake Value ◽  
Emission Tomography ◽  
Positron Emission ◽  
Short Course ◽  
Measurable Amount ◽  
The Central Nervous System ◽  
The Brain

Objective: To assess whether intravenous immunoglobulin (IVIG) in subjects with mild cognitive impairment (MCI) results in a reduction in amyloid in the central nervous system (CNS). Methods: Five subjects with MCI underwent baseline Florbetapir positron emission tomography and retinal autofluorescent imaging. All were administered IVIG (Octagam 10%) at 0.4 g/kg every 14 days for a total of 5 infusions. After 3 months, standard uptake value ratio (SUVR) and amyloid retinal deposits were reassessed. Results: Three subjects had a reduction in amyloid SUVR and all 5 subjects had a reduction in amyloid retinal deposits in at least 1 eye. Conclusions: A short course of IVIG over 2 months removes a measurable amount of amyloid from the CNS in persons with MCI.

Evolution of Brain Glucose Metabolic Abnormalities in Children With Epilepsy and SCN1A Gene Variants

2018 ◽  
Vol 33 (13) ◽  
pp. 832-836 ◽  
Author(s):  
Ananyaa Kumar ◽  
Csaba Juhász ◽  
Aimee Luat ◽  
Tuhina Govil-Dalela ◽  
Michael E. Behen ◽  
...  
Keyword(s):  
Temporal Cortex ◽  
Occipital Cortex ◽  
Metabolic Pattern ◽  
Brain Glucose ◽  
Fdg Uptake ◽  
Positron Emission ◽  
Pet Scanning ◽  
And Gender ◽  
The Brain

Three children with drug-refractory epilepsy, normal magnetic resonance image (MRI), and a heterozygous SCN1A variant underwent 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography (FDG-PET) scanning between age 6 months and 1 year and then at age 3 years 6 months to 5 years 5 months. Regional FDG uptake values were compared to those measured in age- and gender-matched pseudo-controls. At baseline, the brain glucose metabolic pattern in the SCN1A group was similar to that of the pseudo-controls. At follow-up, robust decreases of normalized FDG uptake was found in bilateral frontal, parietal and temporal cortex, with milder decreases in occipital cortex. Children with epilepsy and an SCN1A variant have a normal pattern of cerebral glucose metabolism at around 1 year of age but develop bilateral cortical glucose hypometabolism by age 4 years, with maximal decreases in frontal, parietal, and temporal cortex. This metabolic pattern may be characteristic of epilepsy associated with SCN1A variants and may serve as a biomarker to monitor disease progression and response to treatments.

scholarly journals Effects of Electroacupuncture at Head Points on the Function of Cerebral Motor Areas in Stroke Patients: A PET Study

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Zuo Fang ◽  
Jia Ning ◽  
Chang Xiong ◽  
Yao Shulin
Keyword(s):  
Ischemic Stroke ◽  
Glucose Metabolism ◽  
Brain Plasticity ◽  
Premotor Cortex ◽  
Good Method ◽  
Motor Area ◽  
Cerebral Function ◽  
Positron Emission ◽  
The Central Nervous System ◽  
The Brain

Positron emission tomography (PET) is used to observe the cerebral function widely and is a good method to explore the mechanism of acupuncture treatment on the central nervous system. By using this method, we observed the cerebral function of 6 patients suffering from ischemic stroke after receiving EA treatment at Baihui(GV20) and right Qubin(GB7). The results were: (1) the glucose metabolism changed significantly on primary motor area (M1), premotor cortex (PMC), and superior parietal louble (LPs) bilaterally, as well as the Supplementary Motor Area (SMA) on the unaffected hemisphere right after the first EA treatment. (2) The glucose metabolism on bilateral M1 and LPs changed significantly after three weeks of daily EA treatments. (3) The glucose metabolism on other areas such as insula, putamen, and cerebellum changed significantly. It demonstrated that EA at Qubin and Baihui couldactivate the cerebral structures related to motor function on the bilateral hemispheres.We concluded that EA was very helpful for the cerebral motor plasticity after the ischemic stroke. Also based on this study we assumed that the brain plasticity should be a network and that acupuncture participated in some sections of this course.

scholarly journals Glucagon-Like Peptide-1 Decreases Intracerebral Glucose Content by Activating Hexokinase and Changing Glucose Clearance during Hyperglycemia

2012 ◽  
Vol 32 (12) ◽  
pp. 2146-2152 ◽  
Author(s):  
Michael Gejl ◽  
Lærke Egefjord ◽  
Susanne Lerche ◽  
Kim Vang ◽  
Bo Martin Bibby ◽  
...  
Keyword(s):  
Glucose Content ◽  
Brain Glucose ◽  
Glucose Levels ◽  
Hyperglycemic Clamp ◽  
Positron Emission ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Double Blinded ◽  
The Brain

Type 2 diabetes and hyperglycemia with the resulting increase of glucose concentrations in the brain impair the outcome of ischemic stroke, and may increase the risk of developing Alzheimer's disease (AD). Reports indicate that glucagon-like peptide-1 (GLP-1) may be neuroprotective in models of AD and stroke: Although the mechanism is unclear, glucose homeostasis appears to be important. We conducted a randomized, double-blinded, placebo-controlled crossover study in nine healthy males. Positron emission tomography was used to determine the effect of GLP-1 on cerebral glucose transport and metabolism during a hyperglycemic clamp with 18fluoro-deoxy-glucose as tracer. Glucagon-like peptide-1 lowered brain glucose ( P = 0.023) in all regions. The cerebral metabolic rate for glucose was increased everywhere ( P = 0.039) but not to the same extent in all regions ( P = 0.022). The unidirectional glucose transfer across the blood-brain barrier remained unchanged ( P = 0.099) in all regions, while the unidirectional clearance and the phosphorylation rate increased ( P = 0.013 and 0.017), leading to increased net clearance of the glucose tracer ( P = 0.006). We show that GLP-1 plays a role in a regulatory mechanism involved in the actions of GLUT1 and glucose metabolism: GLP-1 ensures less fluctuation of brain glucose levels in response to alterations in plasma glucose, which may prove to be neuroprotective during hyperglycemia.

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