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2 results on '"Mouse Metabolic Phenotyping Center Imaging Working Group"'

1. Reduced cognitive function, increased blood-brain-barrier transport and inflammatory responses, and altered brain metabolites in LDLr -/-and C57BL/6 mice fed a western diet.

Author

Rutkowsky, Jennifer M, Lee, Linda L, Puchowicz, Michelle, Golub, Mari S, Befroy, Douglas E, Wilson, Dennis W, Anderson, Steven, Cline, Gary, Bini, Jason, Borkowski, Kamil, Knotts, Trina A, Rutledge, John C, and Mouse Metabolic Phenotyping Center Imaging Working Group

Subjects
Mouse Metabolic Phenotyping Center Imaging Working Group, Blood-Brain Barrier, Brain, Animals, Mice, Inbred C57BL, Mice, Knockout, Mice, Receptors, LDL, Cognition, Diet, Western, Diet, Western, Inbred C57BL, Knockout, Receptors, LDL, General Science & Technology
Abstract

Recent work suggests that diet affects brain metabolism thereby impacting cognitive function. Our objective was to determine if a western diet altered brain metabolism, increased blood-brain barrier (BBB) transport and inflammation, and induced cognitive impairment in C57BL/6 (WT) mice and low-density lipoprotein receptor null (LDLr -/-) mice, a model of hyperlipidemia and cognitive decline. We show that a western diet and LDLr -/- moderately influence cognitive processes as assessed by Y-maze and radial arm water maze. Also, western diet significantly increased BBB transport, as well as microvessel factor VIII in LDLr -/- and microglia IBA1 staining in WT, both indicators of activation and neuroinflammation. Interestingly, LDLr -/- mice had a significant increase in 18F- fluorodeoxyglucose uptake irrespective of diet and brain 1H-magnetic resonance spectroscopy showed increased lactate and lipid moieties. Metabolic assessments of whole mouse brain by GC/MS and LC/MS/MS showed that a western diet altered brain TCA cycle and β-oxidation intermediates, levels of amino acids, and complex lipid levels and elevated proinflammatory lipid mediators. Our study reveals that the western diet has multiple impacts on brain metabolism, physiology, and altered cognitive function that likely manifest via multiple cellular pathways.

Published
2018

2. Reduced cognitive function, increased blood-brain-barrier transport and inflammatory responses, and altered brain metabolites in LDLr -/-and C57BL/6 mice fed a western diet

Author

Jennifer M Rutkowsky, Linda L Lee, Michelle Puchowicz, Mari S Golub, Douglas E Befroy, Dennis W Wilson, Steven Anderson, Gary Cline, Jason Bini, Kamil Borkowski, Trina A Knotts, John C Rutledge, Mouse Metabolic Phenotyping Center Imaging Working Group, and Deli, Mária A

Subjects
0301 basic medicine, lcsh:Medicine, Pathology and Laboratory Medicine, Inbred C57BL, Biochemistry, chemistry.chemical_compound, Mice, 0302 clinical medicine, Cognition, Glucose Metabolism, Receptors, Medicine and Health Sciences, 2.1 Biological and endogenous factors, Cognitive decline, Aetiology, lcsh:Science, Immune Response, Cognitive Impairment, Mice, Knockout, 2. Zero hunger, Multidisciplinary, Cognitive Neurology, Mouse Metabolic Phenotyping Center Imaging Working Group, Fatty Acids, Brain, Lipids, Cholesterol, medicine.anatomical_structure, Neurology, Blood-Brain Barrier, Neurological, Carbohydrate Metabolism, Western, Research Article, medicine.medical_specialty, General Science & Technology, Cognitive Neuroscience, Knockout, 1.1 Normal biological development and functioning, Immunology, Blood–brain barrier, Proinflammatory cytokine, LDL, 03 medical and health sciences, Signs and Symptoms, Diagnostic Medicine, Underpinning research, Internal medicine, medicine, Animals, Neuroinflammation, Nutrition, Inflammation, lcsh:R, Neurosciences, Biology and Life Sciences, Lipid metabolism, Lipid Metabolism, Diet, Brain Disorders, Mice, Inbred C57BL, Metabolism, 030104 developmental biology, Endocrinology, Receptors, LDL, chemistry, Diet, Western, LDL receptor, Cognitive Science, lcsh:Q, 030217 neurology & neurosurgery, Neuroscience, Lipoprotein
Abstract

Recent work suggests that diet affects brain metabolism thereby impacting cognitive function. Our objective was to determine if a western diet altered brain metabolism, increased blood-brain barrier (BBB) transport and inflammation, and induced cognitive impairment in C57BL/6 (WT) mice and low-density lipoprotein receptor null (LDLr -/-) mice, a model of hyperlipidemia and cognitive decline. We show that a western diet and LDLr -/- moderately influence cognitive processes as assessed by Y-maze and radial arm water maze. Also, western diet significantly increased BBB transport, as well as microvessel factor VIII in LDLr -/- and microglia IBA1 staining in WT, both indicators of activation and neuroinflammation. Interestingly, LDLr -/- mice had a significant increase in 18F- fluorodeoxyglucose uptake irrespective of diet and brain 1H-magnetic resonance spectroscopy showed increased lactate and lipid moieties. Metabolic assessments of whole mouse brain by GC/MS and LC/MS/MS showed that a western diet altered brain TCA cycle and β-oxidation intermediates, levels of amino acids, and complex lipid levels and elevated proinflammatory lipid mediators. Our study reveals that the western diet has multiple impacts on brain metabolism, physiology, and altered cognitive function that likely manifest via multiple cellular pathways.

Published
2018

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