Metabolic Changes Associated with a Rat Model of Diabetic Depression Detected by Ex Vivo 1H Nuclear Magnetic Resonance Spectroscopy in the Prefrontal Cortex, Hippocampus, and Hypothalamus

Diabetic patients often present with comorbid depression. However, the pathogenetic mechanisms underlying diabetic depression (DD) remain unclear. To explore the mechanisms underpinning the pathogenesis of the disease, we used ex vivo 1H nuclear magnetic resonance spectroscopy and immunohistochemist...

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Main Authors: Kun Liu, Liangcai Zhao, Wen Xu, Qiuting Lin, Yongjin Zhou, Xiaoyan Huang, Xinjian Ye, Jiawei He, Guanghui Bai, Zhihan Yan, Hongchang Gao
Format: Article
Language:English
Published: Wiley 2018-01-01
Series:Neural Plasticity
Online Access:http://dx.doi.org/10.1155/2018/6473728
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author Kun Liu
Liangcai Zhao
Wen Xu
Qiuting Lin
Yongjin Zhou
Xiaoyan Huang
Xinjian Ye
Jiawei He
Guanghui Bai
Zhihan Yan
Hongchang Gao
author_facet Kun Liu
Liangcai Zhao
Wen Xu
Qiuting Lin
Yongjin Zhou
Xiaoyan Huang
Xinjian Ye
Jiawei He
Guanghui Bai
Zhihan Yan
Hongchang Gao
author_sort Kun Liu
collection DOAJ
description Diabetic patients often present with comorbid depression. However, the pathogenetic mechanisms underlying diabetic depression (DD) remain unclear. To explore the mechanisms underpinning the pathogenesis of the disease, we used ex vivo 1H nuclear magnetic resonance spectroscopy and immunohistochemistry to investigate the main metabolic and pathological changes in various rat brain areas in an animal model of DD. Compared with the control group, rats in the DD group showed significant decreases in neurotransmitter concentrations of glutamate (Glu) and glutamine (Gln) in the prefrontal cortex (PFC), hippocampus, and hypothalamus and aspartate and glycine in the PFC and hypothalamus. Gamma-aminobutyric acid (GABA) was decreased only in the hypothalamus. Levels of the energy product, lactate, were higher in the PFC, hippocampus, and hypothalamus of rats with DD than those in control rats, while creatine was lower in the PFC and hippocampus, and alanine was lower in the hypothalamus. The levels of other brain metabolites were altered, including N-acetyl aspartate, taurine, and choline. Immunohistochemistry analysis revealed that expressions of both glutamine synthetase and glutaminase were decreased in the PFC, hippocampus, and hypothalamus of rats with DD. The metabolic changes in levels of Glu, Gln, and GABA indicate an imbalance of the Glu-Gln metabolic cycle between astrocytes and neurons. Our results suggest that the development of DD in rats may be linked to brain metabolic changes, including inhibition of the Glu-Gln cycle, increases in anaerobic glycolysis, and disturbances in the lactate-alanine shuttle, and associated with dysfunction of neurons and astrocytes.
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spelling doaj-art-e8bfaad4a27640dd8f3b9aca099153f72025-08-20T02:22:01ZengWileyNeural Plasticity2090-59041687-54432018-01-01201810.1155/2018/64737286473728Metabolic Changes Associated with a Rat Model of Diabetic Depression Detected by Ex Vivo 1H Nuclear Magnetic Resonance Spectroscopy in the Prefrontal Cortex, Hippocampus, and HypothalamusKun Liu0Liangcai Zhao1Wen Xu2Qiuting Lin3Yongjin Zhou4Xiaoyan Huang5Xinjian Ye6Jiawei He7Guanghui Bai8Zhihan Yan9Hongchang Gao10Radiology Department of the Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou 325035, ChinaSchool of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, ChinaRadiology Department of the Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou 325035, ChinaSchool of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, ChinaRadiology Department of the Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou 325035, ChinaRadiology Department of the Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou 325035, ChinaRadiology Department of the Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou 325035, ChinaRadiology Department of the Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou 325035, ChinaRadiology Department of the Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou 325035, ChinaRadiology Department of the Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou 325035, ChinaSchool of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, ChinaDiabetic patients often present with comorbid depression. However, the pathogenetic mechanisms underlying diabetic depression (DD) remain unclear. To explore the mechanisms underpinning the pathogenesis of the disease, we used ex vivo 1H nuclear magnetic resonance spectroscopy and immunohistochemistry to investigate the main metabolic and pathological changes in various rat brain areas in an animal model of DD. Compared with the control group, rats in the DD group showed significant decreases in neurotransmitter concentrations of glutamate (Glu) and glutamine (Gln) in the prefrontal cortex (PFC), hippocampus, and hypothalamus and aspartate and glycine in the PFC and hypothalamus. Gamma-aminobutyric acid (GABA) was decreased only in the hypothalamus. Levels of the energy product, lactate, were higher in the PFC, hippocampus, and hypothalamus of rats with DD than those in control rats, while creatine was lower in the PFC and hippocampus, and alanine was lower in the hypothalamus. The levels of other brain metabolites were altered, including N-acetyl aspartate, taurine, and choline. Immunohistochemistry analysis revealed that expressions of both glutamine synthetase and glutaminase were decreased in the PFC, hippocampus, and hypothalamus of rats with DD. The metabolic changes in levels of Glu, Gln, and GABA indicate an imbalance of the Glu-Gln metabolic cycle between astrocytes and neurons. Our results suggest that the development of DD in rats may be linked to brain metabolic changes, including inhibition of the Glu-Gln cycle, increases in anaerobic glycolysis, and disturbances in the lactate-alanine shuttle, and associated with dysfunction of neurons and astrocytes.http://dx.doi.org/10.1155/2018/6473728
spellingShingle Kun Liu
Liangcai Zhao
Wen Xu
Qiuting Lin
Yongjin Zhou
Xiaoyan Huang
Xinjian Ye
Jiawei He
Guanghui Bai
Zhihan Yan
Hongchang Gao
Metabolic Changes Associated with a Rat Model of Diabetic Depression Detected by Ex Vivo 1H Nuclear Magnetic Resonance Spectroscopy in the Prefrontal Cortex, Hippocampus, and Hypothalamus
Neural Plasticity
title Metabolic Changes Associated with a Rat Model of Diabetic Depression Detected by Ex Vivo 1H Nuclear Magnetic Resonance Spectroscopy in the Prefrontal Cortex, Hippocampus, and Hypothalamus
title_full Metabolic Changes Associated with a Rat Model of Diabetic Depression Detected by Ex Vivo 1H Nuclear Magnetic Resonance Spectroscopy in the Prefrontal Cortex, Hippocampus, and Hypothalamus
title_fullStr Metabolic Changes Associated with a Rat Model of Diabetic Depression Detected by Ex Vivo 1H Nuclear Magnetic Resonance Spectroscopy in the Prefrontal Cortex, Hippocampus, and Hypothalamus
title_full_unstemmed Metabolic Changes Associated with a Rat Model of Diabetic Depression Detected by Ex Vivo 1H Nuclear Magnetic Resonance Spectroscopy in the Prefrontal Cortex, Hippocampus, and Hypothalamus
title_short Metabolic Changes Associated with a Rat Model of Diabetic Depression Detected by Ex Vivo 1H Nuclear Magnetic Resonance Spectroscopy in the Prefrontal Cortex, Hippocampus, and Hypothalamus
title_sort metabolic changes associated with a rat model of diabetic depression detected by ex vivo 1h nuclear magnetic resonance spectroscopy in the prefrontal cortex hippocampus and hypothalamus
url http://dx.doi.org/10.1155/2018/6473728
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