Hyperpolarized [1-13C] pyruvate MR spectroscopy detect altered glycolysis in the brain of a cognitively impaired mouse model fed high-fat diet 11 Medical and Health Sciences 1109 Neurosciences 11 Medical and Health Sciences 1103 Clinical Sciences

Young Suk Choi, Somang Kang, Sang Yoon Ko, Saeram Lee, Jae Young Kim, Hansol Lee, Jae Eun Song, Dong Hyun Kim, Eosu Kim, Chul Hoon Kim, Lisa Saksida, Ho Taek Song, Jong Eun Lee

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Higher dietary intakes of saturated fatty acid increase the risk of developing Alzheimer's disease and dementia, and even in people without diabetes higher glucose levels may be a risk factor for dementia. The mechanisms causing neuronal dysfunction and dementia by consuming high-fat diet degrading the integrity of the blood-brain barrier (BBB) has been suggested but are not yet fully understood, and metabolic state of the brain by this type of insult is still veiled. The objective of this study was to investigate the effect of high-fat diet on the brain metabolism by a multimodal imaging method using the hyperpolarizedcarbon 13 ( 13 C)-pyruvate magnetic resonance (MR) spectroscopy and dynamic contrast-enhanced MR imaging in conjunction with the biochemical assay and the behavior test in a mouse model fed high-fat diet (HFD). In mice were fed 60% HFD for 6 months, hyperpolarized [1- 13 C] pyruvate MR spectroscopy showed decreased perfusion (p < 0.01) and increased conversion from pyruvate to lactate (p < 0.001) in the brain. The hippocampus and striatum showed the highest conversion ratio. The functional integrity of the blood-brain barrier tested by dynamic contrast-enhanced MR imaging showed no difference to the control. Lactate was increased in the cortex (p < 0.01) and striatum (p < 0.05), while PDH activity was decreased in the cortex (p < 0.01) and striatum (p < 0.001) and the phosphorylated PDH was increased in the striatum (p < 0.05). Mice fed HFD showed less efficiency in learning memory compared with control (p < 0.05). To determine whether hyperpolarized 13 C-pyruvate magnetic resonance (MR) spectroscopy could detect a much earier event in the brain. Mice fed HFD for 3 months did not show a detectable cognitive decline in water maze based learning memory. Hyperpolarized [1- 13 C] pyruvate MR spectroscopy showed increased lactate conversion (P <.001), but no difference in cerebral perfusion. These results suggest that the increased hyperpolarized [1- 13 C] lactate signal in the brain of HFD-fed mice represent that altered metabolic alteration toward to glycolysis and hypoperfusion by the long-term metabolic stress by HFD further promote to glycolysis. The hyperpolarized [1- 13 C] pyruvate MR spectroscopy can be used to monitor the brain metabolism and will provide information helpful to understand the disease process.

Original languageEnglish
Article number74
JournalMolecular Brain
Volume11
Issue number1
DOIs
Publication statusPublished - 2018 Dec 18

Fingerprint

High Fat Diet
Glycolysis
Neurosciences
Pyruvic Acid
Magnetic Resonance Spectroscopy
Health
Brain
Lactic Acid
Blood-Brain Barrier
Dementia
Alzheimer Disease
Perfusion
Multimodal Imaging
Magnetic Resonance Imaging
Maze Learning
Physiological Stress
Hippocampus
Fatty Acids
Learning
Efficiency

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cellular and Molecular Neuroscience

Cite this

Choi, Young Suk ; Kang, Somang ; Ko, Sang Yoon ; Lee, Saeram ; Kim, Jae Young ; Lee, Hansol ; Song, Jae Eun ; Kim, Dong Hyun ; Kim, Eosu ; Kim, Chul Hoon ; Saksida, Lisa ; Song, Ho Taek ; Lee, Jong Eun. / Hyperpolarized [1-13C] pyruvate MR spectroscopy detect altered glycolysis in the brain of a cognitively impaired mouse model fed high-fat diet 11 Medical and Health Sciences 1109 Neurosciences 11 Medical and Health Sciences 1103 Clinical Sciences. In: Molecular Brain. 2018 ; Vol. 11, No. 1.
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abstract = "Higher dietary intakes of saturated fatty acid increase the risk of developing Alzheimer's disease and dementia, and even in people without diabetes higher glucose levels may be a risk factor for dementia. The mechanisms causing neuronal dysfunction and dementia by consuming high-fat diet degrading the integrity of the blood-brain barrier (BBB) has been suggested but are not yet fully understood, and metabolic state of the brain by this type of insult is still veiled. The objective of this study was to investigate the effect of high-fat diet on the brain metabolism by a multimodal imaging method using the hyperpolarizedcarbon 13 ( 13 C)-pyruvate magnetic resonance (MR) spectroscopy and dynamic contrast-enhanced MR imaging in conjunction with the biochemical assay and the behavior test in a mouse model fed high-fat diet (HFD). In mice were fed 60{\%} HFD for 6 months, hyperpolarized [1- 13 C] pyruvate MR spectroscopy showed decreased perfusion (p < 0.01) and increased conversion from pyruvate to lactate (p < 0.001) in the brain. The hippocampus and striatum showed the highest conversion ratio. The functional integrity of the blood-brain barrier tested by dynamic contrast-enhanced MR imaging showed no difference to the control. Lactate was increased in the cortex (p < 0.01) and striatum (p < 0.05), while PDH activity was decreased in the cortex (p < 0.01) and striatum (p < 0.001) and the phosphorylated PDH was increased in the striatum (p < 0.05). Mice fed HFD showed less efficiency in learning memory compared with control (p < 0.05). To determine whether hyperpolarized 13 C-pyruvate magnetic resonance (MR) spectroscopy could detect a much earier event in the brain. Mice fed HFD for 3 months did not show a detectable cognitive decline in water maze based learning memory. Hyperpolarized [1- 13 C] pyruvate MR spectroscopy showed increased lactate conversion (P <.001), but no difference in cerebral perfusion. These results suggest that the increased hyperpolarized [1- 13 C] lactate signal in the brain of HFD-fed mice represent that altered metabolic alteration toward to glycolysis and hypoperfusion by the long-term metabolic stress by HFD further promote to glycolysis. The hyperpolarized [1- 13 C] pyruvate MR spectroscopy can be used to monitor the brain metabolism and will provide information helpful to understand the disease process.",
author = "Choi, {Young Suk} and Somang Kang and Ko, {Sang Yoon} and Saeram Lee and Kim, {Jae Young} and Hansol Lee and Song, {Jae Eun} and Kim, {Dong Hyun} and Eosu Kim and Kim, {Chul Hoon} and Lisa Saksida and Song, {Ho Taek} and Lee, {Jong Eun}",
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Hyperpolarized [1-13C] pyruvate MR spectroscopy detect altered glycolysis in the brain of a cognitively impaired mouse model fed high-fat diet 11 Medical and Health Sciences 1109 Neurosciences 11 Medical and Health Sciences 1103 Clinical Sciences. / Choi, Young Suk; Kang, Somang; Ko, Sang Yoon; Lee, Saeram; Kim, Jae Young; Lee, Hansol; Song, Jae Eun; Kim, Dong Hyun; Kim, Eosu; Kim, Chul Hoon; Saksida, Lisa; Song, Ho Taek; Lee, Jong Eun.

In: Molecular Brain, Vol. 11, No. 1, 74, 18.12.2018.

Research output: Contribution to journalArticle

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T1 - Hyperpolarized [1-13C] pyruvate MR spectroscopy detect altered glycolysis in the brain of a cognitively impaired mouse model fed high-fat diet 11 Medical and Health Sciences 1109 Neurosciences 11 Medical and Health Sciences 1103 Clinical Sciences

AU - Choi, Young Suk

AU - Kang, Somang

AU - Ko, Sang Yoon

AU - Lee, Saeram

AU - Kim, Jae Young

AU - Lee, Hansol

AU - Song, Jae Eun

AU - Kim, Dong Hyun

AU - Kim, Eosu

AU - Kim, Chul Hoon

AU - Saksida, Lisa

AU - Song, Ho Taek

AU - Lee, Jong Eun

PY - 2018/12/18

Y1 - 2018/12/18

N2 - Higher dietary intakes of saturated fatty acid increase the risk of developing Alzheimer's disease and dementia, and even in people without diabetes higher glucose levels may be a risk factor for dementia. The mechanisms causing neuronal dysfunction and dementia by consuming high-fat diet degrading the integrity of the blood-brain barrier (BBB) has been suggested but are not yet fully understood, and metabolic state of the brain by this type of insult is still veiled. The objective of this study was to investigate the effect of high-fat diet on the brain metabolism by a multimodal imaging method using the hyperpolarizedcarbon 13 ( 13 C)-pyruvate magnetic resonance (MR) spectroscopy and dynamic contrast-enhanced MR imaging in conjunction with the biochemical assay and the behavior test in a mouse model fed high-fat diet (HFD). In mice were fed 60% HFD for 6 months, hyperpolarized [1- 13 C] pyruvate MR spectroscopy showed decreased perfusion (p < 0.01) and increased conversion from pyruvate to lactate (p < 0.001) in the brain. The hippocampus and striatum showed the highest conversion ratio. The functional integrity of the blood-brain barrier tested by dynamic contrast-enhanced MR imaging showed no difference to the control. Lactate was increased in the cortex (p < 0.01) and striatum (p < 0.05), while PDH activity was decreased in the cortex (p < 0.01) and striatum (p < 0.001) and the phosphorylated PDH was increased in the striatum (p < 0.05). Mice fed HFD showed less efficiency in learning memory compared with control (p < 0.05). To determine whether hyperpolarized 13 C-pyruvate magnetic resonance (MR) spectroscopy could detect a much earier event in the brain. Mice fed HFD for 3 months did not show a detectable cognitive decline in water maze based learning memory. Hyperpolarized [1- 13 C] pyruvate MR spectroscopy showed increased lactate conversion (P <.001), but no difference in cerebral perfusion. These results suggest that the increased hyperpolarized [1- 13 C] lactate signal in the brain of HFD-fed mice represent that altered metabolic alteration toward to glycolysis and hypoperfusion by the long-term metabolic stress by HFD further promote to glycolysis. The hyperpolarized [1- 13 C] pyruvate MR spectroscopy can be used to monitor the brain metabolism and will provide information helpful to understand the disease process.

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