scholarly journals Clozapine Induces Astrocyte-Dependent FDG-PET Hypometabolism

2021 ◽  
Author(s):  
Andreia Silva da Rocha ◽  
Bruna Bellaver ◽  
Débora G. Souza ◽  
Guilherme Schu ◽  
Igor Camargo Fontana ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Fdg Pet ◽  
Glutamate Uptake ◽  
Neuronal Uptake ◽  
Neuronal Cultures ◽  
Lactate Shuttle ◽  
Brain Glucose ◽  
Brain Glucose Metabolism

Abstract Purpose Advances in functional imaging allowed us to visualize brain glucose metabolism in vivo and non-invasively with [18F]fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) imaging. In the past decades, FDG-PET has been instrumental in the understanding of brain function in health and disease. The source of the FDG-PET signal has been attributed to neuronal uptake, with hypometabolism being considered as a direct index of neuronal dysfunction or death. However, other brain cells are also metabolically active, including astrocytes. Based on the astrocyte-neuron lactate shuttle hypothesis, the activation of the glutamate transporter 1 (GLT-1) acts as a trigger for glucose uptake by astrocytes. With this in mind, we investigated glucose utilization changes after pharmacologically downregulating GLT-1 with clozapine (CLO), an antipsychotic drug. Methods Adult male Wistar rats (control, n = 14; CLO, n = 12) received CLO (25/35mg kg−1) for six weeks. CLO effects were evaluated in vivo with FDG-PET and cortical tissue was used to evaluate glutamate uptake, GLT-1 and GLAST levels. CLO treatment effects were also assessed in cortical astrocyte cultures (glucose and glutamate uptake, GLT-1 and GLAST levels) and in cortical neuronal cultures (glucose uptake). Results CLO markedly reduced in vivo brain glucose metabolism in several brain areas, especially in the cortex. Ex vivo analyses demonstrated decreased cortical glutamate transport along with GLT-1 mRNA and protein downregulation. In astrocyte cultures, CLO decreased GLT-1 density as well as glutamate and glucose uptake. By contrast, in cortical neuronal cultures, CLO did not affect glucose uptake. Conclusion This work provides in vivo demonstration that GLT-1 downregulation induces astrocyte-dependent cortical FDG-PET hypometabolism - mimicking the hypometabolic signature seen in people developing dementia - and adds further evidence that astrocytes are key contributors of the FDG-PET signal.

scholarly journals The impact of a multi-domain intervention on cerebral glucose metabolism: analysis from the randomized ancillary FDG PET MAPT trial

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Julien Delrieu ◽  
Thierry Voisin ◽  
Laure Saint-Aubert ◽  
Isabelle Carrie ◽  
Christelle Cantet ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Fdg Pet ◽  
Primary Outcome ◽  
Cognitive Stimulation ◽  
Cerebral Glucose Metabolism ◽  
Parahippocampal Gyrus ◽  
Cerebral Magnetic Resonance Imaging ◽  
Brain Glucose ◽  
Brain Glucose Metabolism ◽  
The Impact

Abstract Background The Multidomain Alzheimer Preventive Trial (MAPT) was designed to assess the efficacy of omega-3 fatty acid supplementation, multidomain intervention (MI), or a combination of both on cognition. Although the MAPT study was negative, an effect of MI in maintaining cognitive functions compared to placebo group was showed in positive amyloid subjects. A FDG PET study (MAPT-NI) was implemented to test the impact of MI on brain glucose metabolism. Methods MAPT-NI was a randomized, controlled parallel-group single-center study, exploring the effect of MI on brain glucose metabolism. Participants were non-demented and had memory complaints, limitation in one instrumental activity of daily living, or slow gait. Participants were randomly assigned (1:1) to “MI group” or “No MI group.” The MI consisted of group sessions focusing on 3 domains: cognitive stimulation, physical activity, nutrition, and a preventive consultation. [18F]FDG PET scans were performed at baseline, 6 months, and 12 months, and cerebral magnetic resonance imaging scans at baseline. The primary objective was to evaluate the MI effect on brain glucose metabolism assessed by [18F]FDG PET imaging at 6 months. The primary outcome was the quantification of regional metabolism rate for glucose in cerebral regions involved early in Alzheimer disease by relative semi-quantitative SUVr (FDG-based AD biomarker). An exploratory voxel-wise analysis was performed to assess the effect of MI on brain glucose metabolism without anatomical hypothesis. Results The intention-to-treat population included 67 subjects (34 in the MI group and 33 in the No MI group. No significant MI effect was observed on primary outcome at 6 months. In the exploratory voxel-wise analysis, we observed a difference in favor of MI group on the change of cerebral glucose metabolism in limbic lobe (right hippocampus, right posterior cingulate, left posterior parahippocampal gyrus) at 6 months. Conclusions MI failed to show an effect on metabolism in FDG-based AD biomarker, but exploratory analysis suggested positive effect on limbic system metabolism. This finding could suggest a delay effect of MI on AD progression. Trial registration ClinicalTrials.gov Identifier, NCT01513252.

scholarly journals Brain Glucose Metabolism in Health, Obesity, and Cognitive Decline—Does Insulin Have Anything to Do with It? A Narrative Review

2021 ◽  
Vol 10 (7) ◽  
pp. 1532
Author(s):  
Eleni Rebelos ◽  
Juha O. Rinne ◽  
Pirjo Nuutila ◽  
Laura L. Ekblad
Keyword(s):  
Insulin Resistance ◽  
Glucose Metabolism ◽  
Cognitive Decline ◽  
Fdg Pet ◽  
Metabolic Disorders ◽  
Brain Glucose ◽  
Brain Glucose Metabolism ◽  
Systemic Insulin Resistance ◽  
Increased Risk ◽  
18F Fdg

Imaging brain glucose metabolism with fluorine-labelled fluorodeoxyglucose ([18F]-FDG) positron emission tomography (PET) has long been utilized to aid the diagnosis of memory disorders, in particular in differentiating Alzheimer’s disease (AD) from other neurological conditions causing cognitive decline. The interest for studying brain glucose metabolism in the context of metabolic disorders has arisen more recently. Obesity and type 2 diabetes—two diseases characterized by systemic insulin resistance—are associated with an increased risk for AD. Along with the well-defined patterns of fasting [18F]-FDG-PET changes that occur in AD, recent evidence has shown alterations in fasting and insulin-stimulated brain glucose metabolism also in obesity and systemic insulin resistance. Thus, it is important to clarify whether changes in brain glucose metabolism are just an epiphenomenon of the pathophysiology of the metabolic and neurologic disorders, or a crucial determinant of their pathophysiologic cascade. In this review, we discuss the current knowledge regarding alterations in brain glucose metabolism, studied with [18F]-FDG-PET from metabolic disorders to AD, with a special focus on how manipulation of insulin levels affects brain glucose metabolism in health and in systemic insulin resistance. A better understanding of alterations in brain glucose metabolism in health, obesity, and neurodegeneration, and the relationships between insulin resistance and central nervous system glucose metabolism may be an important step for the battle against metabolic and cognitive disorders.

Altered brain glucose metabolism in transgenic-PFKL mice with elevated l-phosphofructokinase: in vivo NMR studies

1998 ◽  
Vol 810 (1-2) ◽  
pp. 138-145 ◽  
Author(s):  
Mira Peled-Kamar ◽  
Hadassa Degani ◽  
Peter Bendel ◽  
Ra'anan Margalit ◽  
Yoram Groner
Keyword(s):  
Glucose Metabolism ◽  
Nmr Studies ◽  
Brain Glucose ◽  
Brain Glucose Metabolism ◽  
In Vivo Nmr

scholarly journals The Impact of A Multi-Domain Intervention on Cerebral Glucose Metabolism: Analysis from the Randomized Ancillary FDG PET MAPT trial

2020 ◽  
Author(s):  
Julien Delrieu ◽  
Thierry Voisin ◽  
Laure Saint-Aubert ◽  
Isabelle Carrie ◽  
Christelle Cantet ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Fdg Pet ◽  
Primary Outcome ◽  
Cognitive Stimulation ◽  
Cerebral Glucose Metabolism ◽  
Parahippocampal Gyrus ◽  
Cerebral Magnetic Resonance Imaging ◽  
Brain Glucose ◽  
Brain Glucose Metabolism ◽  
The Impact

Abstract Background: The Multidomain Alzheimer Preventive Trial (MAPT) was designed to assess the efficacy of omega-3 fatty acid supplementation, multidomain intervention (MI), or a combination of both on cognition. Although the MAPT study was negative, an effect of MI in maintaining cognitive functions compared to placebo group was showed in positive amyloid subjects. A FDG PET study (MAPT-NI) was implemented to test the impact of MI on brain glucose metabolism.Methods: MAPT-NI was a randomized, controlled parallel-group single-center study, exploring the effect of MI on brain glucose metabolism. Participants were non-demented, and had memory complaints, limitation in one instrumental activity of daily living, or slow gait. Participants were randomly assigned (1:1) to « MI group » or « No MI group ». The MI consisted of group sessions focusing on 3 domains: cognitive stimulation, physical activity, nutrition, and a preventive consultation. [18F]FDG PET scans were performed at baseline, 6 months and 12 months, and cerebral Magnetic Resonance Imaging scans at baseline The primary objective was to evaluate the MI effect on brain glucose metabolism assessed by [18F]FDG PET imaging at 6 months. The primary outcome was the quantification of regional metabolism rate for glucose in cerebral regions involved early in Alzheimer disease by relative semi-quantitative SUVr (FDG-based AD biomarker). An exploratory voxel-wise analysis was performed to assess the effect of MI on brain glucose metabolism without anatomical hypothesis.Results: The intention-to-treat population included 67 subjects (34 in the « MI group » and 33 in the « No MI group ». No significant MI effect was observed on primary outcome at 6 and 12 months. In the exploratory voxel-wise analysis, we observed a difference in favor of « MI group » on the change of cerebral glucose metabolism in limbic lobe (right hippocampus, right posterior cingulate, left posterior parahippocampal gyrus) at 6 months.Conclusions: MI failed to show an effect on metabolism in FDG-based AD biomarker, but exploratory analysis suggested positive effect on limbic system metabolism. This finding could suggest a delay effect of MI on AD progression.Trial registration: ClinicalTrials.gov Identifier, NCT01513252.

Changes in brain glucose metabolism and connectivity in somatoform disorders: an 18F-FDG PET study

2019 ◽  
Vol 270 (7) ◽  
pp. 881-891 ◽  
Author(s):  
Qi Huang ◽  
Shuhua Ren ◽  
Donglang Jiang ◽  
Yihui Guan ◽  
Fang Xie ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Fdg Pet ◽  
Somatoform Disorders ◽  
Brain Glucose ◽  
Brain Glucose Metabolism ◽  
18F Fdg
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