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Metabolic Brain Disease
Published in: Metabolic Brain Disease 2/2017

01-04-2017 | Original Article

NMR-based metabolomics reveals brain region-specific metabolic alterations in streptozotocin-induced diabetic rats with cognitive dysfunction

Authors: Hong Zheng, Qiuting Lin, Dan Wang, Pengtao Xu, Liangcai Zhao, Wenyi Hu, Guanghui Bai, Zhihan Yan, Hongchang Gao

Published in: Metabolic Brain Disease | Issue 2/2017

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Abstract

Diabetes mellitus (DM) can result in cognitive dysfunction, but its potential metabolic mechanisms remain unclear. In the present study, we analyzed the metabolite profiling in eight different brain regions of the normal rats and the streptozotocin (STZ)-induced diabetic rats accompanied by cognitive dysfunction using a 1H NMR-based metabolomic approach. A mixed linear model analysis was performed to assess the effects of DM, brain region and their interaction on metabolic changes. We found that different brain regions in rats displayed significant metabolic differences. In addition, the hippocampus was more susceptible to DM compared with other brain regions in rats. More interestingly, significant interaction effects of DM and brain region were observed on alanine, creatine/creatine-phosphate, lactate, succinate, aspartate, glutamate, glutamine, γ-aminobutyric acid, glycine, choline, N-acetylaspartate, myo-inositol and taurine. Based on metabolic pathway analysis, we speculate that cognitive dysfunction in the STZ-induced diabetic rats may be associated with brain region-specific metabolic alterations involving energy metabolism, neurotransmitters, membrane metabolism and osmoregulation.
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Literature
Bakker FC, Klijn CJ, Jennekens-Schinkel A, van der Tweel I, van der Grond J, van Huffelen AC, Tulleken CA, Kappelle LJ (2003) Cognitive impairment is related to cerebral lactate in patients with carotid artery occlusion and ipsilateral transient ischemic attacks. Stroke 34(6):1419–1424CrossRefPubMed
Baslow MH (2003) N-acetylaspartate in the vertebrate brain: metabolism and function. Neurochem Res 28(6):941–953CrossRefPubMed
Bélanger M, Allaman I, Magistretti PJ (2011) Brain energy metabolism: focus on astrocyte-neuron metabolic cooperation. Cell Metab 14(6):724–738CrossRefPubMed
Brands AMA, Biessels GJ, Haan EHFD, Kappelle LJ, Kessels RPC (2005) The effects of type 1 diabetes on cognitive performance: a meta-analysis. Diabetes Care 28(3):726–735CrossRefPubMed
Duarte JM, Lei H, Mlynárik V, Gruetter R (2012) The neurochemical profile quantified by in vivo 1H NMR spectroscopy. NeuroImage 61(2):342–362CrossRefPubMed
Gold SM, Dziobek I, Sweat V, Tirsi A, Rogers K, Bruehl H, Tsui W, Richardson S, Javier E, Convit A (2007) Hippocampal damage and memory impairments as possible early brain complications of type 2 diabetes. Diabetologia 50(4):711–719CrossRefPubMed
Hellweg R, Nitsch R, Hock C, Jaksch M, Hoyer S (1992) Nerve growth factor and choline acetyltransferase activity levels in the rat brain following experimental impairment of cerebral glucose and energy metabolism. J Neurosci Res 31(3):479–486CrossRefPubMed
Huerta KC, Téllez GY, Salinas CAA, Díaz JMM (2013) Cognitive function in type 2 diabetes: a review. Salud Mental 36(2):149–157CrossRef
Isaacks RE, Bender AS, Kim CY, Prieto NM, Norenberg MD (1994) Osmotic regulation of myo-inositol uptake in primary astrocyte cultures. Neurochem Res 19(3):331–338CrossRefPubMed
Ivanisevic J, Epstein AA, Kurczy ME, Benton PH, Uritboonthai W, Fox HS, Boska MD, Gendelman HE, Siuzdak G (2014) Brain region mapping using global metabolomics. Chem Biol 21(11):1575–1584CrossRefPubMedPubMedCentral
Kamal A, Biessels GJ, Duis SEJ, Gispen WH (2000) Learning and hippocampal synaptic plasticity in streptozotocin-diabetic rats: interaction of diabetes and ageing. Diabetologia 43(4):500–506CrossRefPubMed
Kim B, Feldman EL (2015) Insulin resistance as a key link for the increased risk of cognitive impairment in the metabolic syndrome. Exp Mol Med 47(3):e149CrossRefPubMedPubMedCentral
Lalandea J, Halleyb H, Balayssaca S (2014) 1H NMR metabolomic signatures in five brain regions of the APPswe Tg2576 mouse model of Alzheimer’s disease at four ages. J Alzheimers Dis 39(1):121–143
Lei Y, Li D, Deng J, Shao WH, Fan SH, Wang X, Huang H, Chen SG, Zhang HZ, Zhang L, Zhang Y, Li WJ, Huang RZ, Liu X, Zhou CJ, Chen JJ, Xie P (2014) Metabolomic profiling of three brain regions from a postnatal infected Borna disease virus Hu-H1 rat model. Metabolomics 10(3):484–495CrossRef
Lenzen S (2008) The mechanisms of alloxan- and streptozotocin-induced diabetes. Diabetologia 51(2):216–226CrossRefPubMed
Liguori C, Stefani A, Sancesario G, Sancesario GM, Marciani MG, Pierantozzi M (2015) CSF lactate levels, τ proteins, cognitive decline: a dynamic relationship in Alzheimer’s disease. J Neurol Neurosurg Psychiatry 86(6):655–659CrossRefPubMed
Liu Y, Liu H, Yang J, Liu X, Lu S, Wen T, Xie L, Wang G (2008) Increased amyloid beta-peptide (1-40) level in brain of streptozotocin-induced diabetic rats. Neuroscience 153(3):796–802CrossRefPubMed
Michel V, Yuan Z, Ramsubir S, Bakovic M (2006) Choline transport for phospholipid synthesis. Exp Biol Med 231(5):490–504
Myhrer T (2003) Neurotransmitter systems involved in learning and memory in the rat: a meta-analysis based on studies of four behavioral tasks. Brain Res Rev 41(2):268–287CrossRefPubMed
Nagayach A, Patro N, Patro I (2014) Astrocytic and microglial response in experimentally induced diabetic rat brain. Metab Brain Dis 29(3):747–761CrossRefPubMed
Ni Y, Su M, Lin J, Wang X, Qiu Y, Zhao A, Chen T, Jia W (2008) Metabolic profiling reveals disorder of amino acid metabolism in four brain regions from a rat model of chronic unpredictable mild stress. FEBS Lett 582(17):2627–2636CrossRefPubMed
OBrien JT, Erkinjuntti T, Reisberg B, Roman G, Sawada T, Pantoni L, Bowler JV, Ballard C, DeCarli C, Gorelick PB, Rockwood K, Burns A, Gauthier S, ST DK (2003) Vascular cognitive impairment. Lancet Neurol 2(2):89–98
Pasantes-Morales H, Schousboe A (1997) Role of taurine in osmoregulation in brain cells: mechanisms and functional implications. Amino Acids 12(3):281–292CrossRef
Paxinos G, Watson C (2005) The rat brain in stereotaxic coordinates. Elsevier Academic Press, Amsterdam
Pugliese M, Carrasco JL, Andrade C, Mas E, Mascort J, Mahy N (2005) Severe cognitive impairment correlates with higher cerebrospinal fluid levels of lactate and pyruvate in a canine model of senile dementia. Prog Neuro-Psychopharmacol Biol Psychiatry 29(4):603–610CrossRef
Redish AD, Touretztky DS (1998) The role of the hippocampus in the Morris water maze. In Computational Neuroscience. Springer US, pp. 101–106
Sharma M, Gupta YK (2001) Intracerebroventricular injection of streptozotocin in rats produces both oxidative stress in the brain and cognitive impairment. Life Sci 68(9):1021–1029CrossRefPubMed
Shingo AS, Kanabayashi T, Murase T, Kito S (2012) Cognitive decline in STZ-3 V rats is largely due to dysfunctional insulin signalling through the dentate gyrus. Behav Brain Res 229(2):378–383CrossRefPubMed
Tao Z, Shi A, Zhao J (2015) Epidemiological perspectives of diabetes. Cell Biochem Biophys 73(1):181–185CrossRefPubMed
van den Berg RA, Hoefsloot HC, Westerhuis JA, Smilde AK, van der Werf MJ (2006) Centering, scaling, and transformations: improving the biological information content of metabolomics data. BMC Genomics 7:142CrossRefPubMedPubMedCentral
Wada H, Okada Y, Uzuo H, Nakamura H (1998) The effects of glucose, mannose, fructose and lactate on the preservation of neural activity in the hippocampal slices from the Guinea pig. Brain Res 788(1):144–150CrossRefPubMed
Willette AA, Xu G, Johnson SC, Birdsill AC, Jonaitis EM, Sager MA, Hermann BP, La Rue A, Asthana S, Bendlin BB (2013) Insulin resistance, brain atrophy, and cognitive performance in late middle–aged adults. Diabetes Care 36(2):443–449CrossRefPubMedPubMedCentral
Wishart DS, Jewison T, Guo AC, Wilson M, Knox C, Liu Y, Djoumbou Y, Mandal R, Aziat F, Dong E, Bouatra S, Sinelnikov I, Arndt D, Xia J, Liu P, Yallou F, Bjorndahl T, Perez-Pineiro R, Eisner R, Allen F, Neveu V, Greiner R, Scalbert A (2012) HMDB 3.0-the human metabolome database in 2013. Nucleic Acids Res 41:801–807CrossRef
Wyss MT, Jolivet R, Buck A, Magistretti PJ, Weber B (2011) In vivo evidence for lactate as a neuronal energy source. J Neurosci 31(20):7477–7485CrossRefPubMed
Yagihashi S, Mizukami H, Sugimoto K (2011) Mechanism of diabetic neuropathy: where are we now and where to go? J Diabetes Invest 2(1):18–32CrossRef
Yamane K, Yokono K, Okada Y (2000) Anaerobic glycolysis is crucial for the maintenance of neural activity in Guinea pig hippocampal slices. J Neurosci Methods 103(2):163–171CrossRefPubMed
Yonguc GN, Ozdemir MB, Küçükatay V, Sahiner M, Akcilar R, Adiguzel E, Akdogan I (2014) Memory function and total pyramidal neuron number of hippocampus in streptozotocin-induced diabetic rats. J Neurol Sci 31(3):461–473
Zheng H, Zhao LC, Xia HH, Xu CC, Wang D, Liu K, Lin L, Li XK, Yan ZH, Gao HC (2016) NMR-based metabolomics reveal a recovery from metabolic changes in the striatum of 6-OHDA-induced rats treated with basic fibroblast growth factor. Mol Neurobiol 53:6690–6697
Zheng H, Zheng YQ, Wang D, Cai AM, Lin QT, Zhao LC, Chen MJ, Deng MJ, Ye XJ, Gao HC (2017) Analysis of neuron-astrocyte metabolic cooperation in the brain of db/db mice with cognitive decline using 13C NMR spectroscopy. J Cereb Blood Flow Metab 37(1):332-343.
Metadata
Title
NMR-based metabolomics reveals brain region-specific metabolic alterations in streptozotocin-induced diabetic rats with cognitive dysfunction
Authors
Hong Zheng
Qiuting Lin
Dan Wang
Pengtao Xu
Liangcai Zhao
Wenyi Hu
Guanghui Bai
Zhihan Yan
Hongchang Gao
Publication date
01-04-2017
Publisher
Springer US
Published in
Metabolic Brain Disease / Issue 2/2017
Print ISSN: 0885-7490
Electronic ISSN: 1573-7365
DOI
https://doi.org/10.1007/s11011-016-9949-0

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