Top

Published in:

20-01-2022 | Intrauterine Growth Restriction | Original Article

Taurine supplementation improves hippocampal metabolism in immature rats with intrauterine growth restriction (IUGR) through protecting neurons and reducing gliosis

Authors: Qiong Fang, Jing Liu, Lang Chen, Qiaobin Chen, Yan Wang, Zuanfang Li, Wei Fu, Ying Liu

Published in: Metabolic Brain Disease | Issue 6/2022

Abstract

Taurine as an essential amino acid in the brain could play an important role in protecting the fetal brain of intrauterine growth restriction (IUGR). The hippocampus with IUGR showed neural metabolic disorder and structure changed that affected memory and learning ability. This study was aimed to identify the effect of taurine supplementation on the metabolism alterations and cellular composition changes of the hippocampus in IUGR immature rats. Metabolite concentrations were determined by magnetic resonance spectroscopy (MRS) in the hippocampus of juvenile rats with IUGR following taurine supplementation with antenatal or postnatal supply. The composition of neural cells in the hippocampus was observed by immunohistochemical staining (IHC) and western blotting (WB). Antenatal taurine supplementation increased the ratios of N-acetylaspartate (NAA) /creatine (Cr) and glutamate (Glu) /Cr of the hippocampus in the IUGR immature rats, but reduced the ratios of choline (Cho) /Cr and myoinositol (mI) /Cr. At the same time, the protein expression of NeuN in the IUGR rats was increased through intrauterine taurine supplementation, and the GFAP expression was reduced. Especially the effect of antenatal taurine was better than postpartum. Furthermore, there existed a positive correlation between the NAA/Cr ratio and the NeuN protein expression (R = 0.496 p < 0.001 IHC; R = 0.568 p < 0.001 WB), the same results existed in the relationship between the mI/Cr ratio and the GFAP protein expression (R = 0.338 p = 0.019 IHC; R = 0.440 p = 0.002 WB). Prenatal taurine supplementation can better improve hippocampal neuronal metabolism by increasing NAA / Cr ratio related to the number of neurons and reducing Cho / Cr ratio related to the number of glial cells.

Amaral AI, Meisingset TW, Kotter MR, Sonnewald U (2013) Metabolic aspects of neuron-oligodendrocyte-astrocyte interactions. Front Endocrinol (Lausanne) 4:54. https://doi.org/10.3389/fendo.2013.00054CrossRef

Batista TM, Ribeiro RA, Amaral AG, de Oliveira CA, Boschero AC, Carneiro EM (2012) Taurine supplementation restores glucose and carbachol-induced insulin secretion in islets from low-protein diet rats: involvement of Ach-M3R, Synt 1 and SNAP-25 proteins. J Nutr Biochem 23:306–312. https://doi.org/10.1016/j.jnutbio.2010.12.012CrossRefPubMed

Bell T, Boudes ES, Loo RS, Barker GJ, Lythgoe DJ, Edden R, Lebel RM, Wilson M, Harris AD (2020) In vivo Glx and Glu measurements from GABA-edited MRS at 3 T. NMR Biomed:e4245. https://doi.org/10.1002/nbm.4245

Bendix I, Miller SL, Winterhager E (2020) Editorial: causes and consequences of intrauterine growth restriction. Front Endocrinol (Lausanne) 11:205. https://doi.org/10.3389/fendo.2020.00205CrossRef

Boschen KE, Criss KJ, Palamarchouk V, Roth TL, Klintsova AY (2015) Effects of developmental alcohol exposure vs. intubation stress on BDNF and TrkB expression in the hippocampus and frontal cortex of neonatal rats. Int J Dev Neurosci 43:16–24. https://doi.org/10.1016/j.ijdevneu.2015.03.008CrossRefPubMedPubMedCentral

Camprubi CM, Balada CR, Ortega CJ, Ortega DLTM, Duran FC, Girabent-Farres M, Figueras-Aloy J, Krauel X, Alcantara S (2017) Learning and memory disabilities in IUGR babies: functional and molecular analysis in a rat model. Brain Behav 7:e631. https://doi.org/10.1002/brb3.631CrossRef

Catherine A (2017) Long-term neurodevelopmental outcomes in small babies. Obstet Gynaecol & Reprod Med 27:235–238. https://doi.org/10.1016/j.ogrm.2017.06.001

Catherine A (2020) Long-term neurodevelopmental outcomes in small babies. Obstet Gynaecol Reprod Med 30

Chen H, Liu J (2009) Effects of intrauterine growth limitation on perinatal brain development. Zhonghua Er Ke Za Zhi 47:33–35PubMed

Dieni S, Rees S (2003) Dendritic morphology is altered in hippocampal neurons following prenatal compromise. J Neurobiol 55:41–52. https://doi.org/10.1002/neu.10194CrossRefPubMed

Eixarch E, Munoz-Moreno E, Bargallo N, Batalle D, Gratacos E (2016) Motor and cortico-striatal-thalamic connectivity alterations in intrauterine growth restriction. Am J Obstet Gynecol 214:721–725. https://doi.org/10.1016/j.ajog.2015.12.028CrossRef

Fung C, Ke X, Brown AS, Yu X, McKnight RA, Lane RH (2012) Uteroplacental insufficiency alters rat hippocampal cellular phenotype in conjunction with ErbB receptor expression. Pediatr Res 72:2–9. https://doi.org/10.1038/pr.2012.32CrossRefPubMedPubMedCentral

Iruloh CG, D'Souza SW, Fergusson WD, Baker PN, Sibley CP, Glazier JD (2009) Amino acid transport systems beta and a in fetal T lymphocytes in intrauterine growth restriction and with tumor necrosis factor-alpha treatment. Pediatr Res 65:51–56. https://doi.org/10.1203/PDR.0b013e31818a0793CrossRefPubMedPubMedCentral

Jansson N, Pettersson J, Haafiz A, Ericsson A, Palmberg I, Tranberg M, Ganapathy V, Powell TL, Jansson T (2006) Down-regulation of placental transport of amino acids precedes the development of intrauterine growth restriction in rats fed a low protein diet. J Physiol 576:935–946. https://doi.org/10.1113/jphysiol.2006.116509CrossRefPubMedPubMedCentral

Kalanjati VP, Wixey JA, Miller SM, Colditz PB, Bjorkman ST (2017) GABAA receptor expression and white matter disruption in intrauterine growth restricted piglets. Int J Dev Neurosci 59:1–9. https://doi.org/10.1016/j.ijdevneu.2017.02.004CrossRefPubMed

Leitner Y, Fattal-Valevski A, Geva R, Eshel R, Toledano-Alhadef H, Rotstein M, Bassan H, Radianu B, Bitchonsky O, Jaffa AJ, Harel S (2007) Neurodevelopmental outcome of children with intrauterine growth retardation: a longitudinal, 10-year prospective study. J Child Neurol 22:580–587. https://doi.org/10.1177/0883073807302605CrossRefPubMed

Li F, Teng HY, Liu J, Wang HW, Zeng L, Zhao LF (2014) Antenatal taurine supplementation increases taurine content in intrauterine growth restricted fetal rat brain tissue. Metab Brain Dis 29:867–871. https://doi.org/10.1007/s11011-014-9532-5CrossRefPubMed

Lister JP, Blatt GJ, DeBassio WA, Kemper TL, Tonkiss J, Galler JR, Rosene DL (2005) Effect of prenatal protein malnutrition on numbers of neurons in the principal cell layers of the adult rat hippocampal formation. Hippocampus 15:393–403. https://doi.org/10.1002/hipo.20065CrossRefPubMed

Liu J, Liu L, Chen H (2011) Antenatal taurine supplementation for improving brain ultrastructure in fetal rats with intrauterine growth restriction. Neuroscience 181:265–270. https://doi.org/10.1016/j.neuroscience.2011.02.056CrossRefPubMed

Liu J, Liu L, Wang XF, Teng HY, Yang N (2012) Antenatal supplementation of taurine for protection of fetal rat brain with intrauterine growth restriction from injury by reducing neuronal apoptosis. Neuropediatrics 43:258–263. https://doi.org/10.1055/s-0032-1324730CrossRefPubMed

Liu J, Liu Y, Wang XF, Chen H, Yang N (2013a) Antenatal taurine supplementation improves cerebral neurogenesis in fetal rats with intrauterine growth restriction through the PKA-CREB signal pathway. Nutr Neurosci 16:282–287. https://doi.org/10.1179/1476830513Y.0000000057CrossRefPubMed

Liu J, Wang X, Liu Y, Yang N, Xu J, Ren X (2013b) Antenatal taurine reduces cerebral cell apoptosis in fetal rats with intrauterine growth restriction. Neural Regen Res 8:2190–2197. https://doi.org/10.3969/j.issn.1673-5374.2013.23.009CrossRefPubMedPubMedCentral

Liu F, Liu Y, Liu J, Ma LY (2015a) Antenatal taurine improves intrauterine growth-restricted fetal rat brain development which is associated with increasing the activity of PKA-CaMKII/c-fos signal pathway. Neuropediatrics 46:299–306. https://doi.org/10.1055/s-0035-1558434CrossRefPubMed

Liu J, Wang HW, Liu F, Wang XF (2015b) Antenatal taurine improves neuronal regeneration in fetal rats with intrauterine growth restriction by inhibiting the Rho-ROCK signal pathway. Metab Brain Dis 30:67–73. https://doi.org/10.1007/s11011-014-9572-xCrossRefPubMed

Lodygensky GA, Seghier ML, Warfield SK, Tolsa CB, Sizonenko S, Lazeyras F, Huppi PS (2008) Intrauterine growth restriction affects the preterm infant's hippocampus. Pediatr Res 63:438–443. https://doi.org/10.1203/PDR.0b013e318165c005CrossRefPubMed

Lu X, Jin C, Yang J, Liu Q, Wu S, Li D, Guan Y, Cai Y (2013) Prenatal and lactational lead exposure enhanced oxidative stress and altered apoptosis status in offspring rats' hippocampus. Biol Trace Elem Res 151:75–84. https://doi.org/10.1007/s12011-012-9531-5CrossRefPubMed

Luthra G, Vuckovic I, Bangdiwala A, Gray H, Redmon JB, Barrett ES, Sathyanarayana S, Nguyen R, Swan SH, Zhang S, Dzeja P, Macura SI, Nair KS (2018) First and second trimester urinary metabolic profiles and fetal growth restriction: an exploratory nested case-control study within the infant development and environment study. BMC Pregnancy Childbirth 18:48. https://doi.org/10.1186/s12884-018-1674-8CrossRefPubMedPubMedCentral

Maia AR, Batista TM, Victorio JA, Clerici SP, Delbin MA, Carneiro EM, Davel AP (2014) Taurine supplementation reduces blood pressure and prevents endothelial dysfunction and oxidative stress in post-weaning protein-restricted rats. PLoS ONE 9:e105851. https://doi.org/10.1371/journal.pone.0105851CrossRefPubMedPubMedCentral

Malhotra A, Castillo-Melendez M, Allison BJ, Sutherland AE, Nitsos I, Pham Y, Alves DARA, Fahey MC, Polglase GR, Jenkin G, Miller SL (2018) Neuropathology as a consequence of neonatal ventilation in premature growth-restricted lambs. Am J Physiol Regul Integr Comp Physiol 315:R1183–R1194. https://doi.org/10.1152/ajpregu.00171.2018CrossRefPubMed

Matthews LG, Smyser CD, Cherkerzian S, Alexopoulos D, Kenley J, Tuuli MG, Nelson DM, Inder TE (2019) Maternal pomegranate juice intake and brain structure and function in infants with intrauterine growth restriction: a randomized controlled pilot study. PLoS ONE 14:e219596. https://doi.org/10.1371/journal.pone.0219596CrossRef

McNamara RK, Able J, Jandacek R, Rider T, Tso P, Lindquist DM (2009) Perinatal n-3 fatty acid deficiency selectively reduces myo-inositol levels in the adult rat PFC: an in vivo (1)H-MRS study. J Lipid Res 50:405–411. https://doi.org/10.1194/jlr.M800382-JLR200CrossRefPubMedPubMedCentral

Miller SL, Yawno T, Alers NO, Castillo-Melendez M, Supramaniam VG, VanZyl N, Sabaretnam T, Loose JM, Drummond GR, Walker DW, Jenkin G, Wallace EM (2014) Antenatal antioxidant treatment with melatonin to decrease newborn neurodevelopmental deficits and brain injury caused by fetal growth restriction. J Pineal Res 56:283–294. https://doi.org/10.1111/jpi.12121CrossRefPubMed

Nardozza LM, Caetano AC, Zamarian AC, Mazzola JB, Silva CP, Marcal VM, Lobo TF, Peixoto AB, Araujo JE (2017) Fetal growth restriction: current knowledge. Arch Gynecol Obstet 295:1061–1077. https://doi.org/10.1007/s00404-017-4341-9CrossRefPubMed

Nealis JG, Rosman NP, De Piero TJ, Ouellette EM (1978) Neurologic sequelae of experimental febrile convulsions. Neurology 28:246–250. https://doi.org/10.1212/wnl.28.3.246CrossRefPubMed

Numano F, Inoue A, Enomoto M, Shinomiya K, Okawa A, Okabe S (2009) Critical involvement of Rho GTPase activity in the efficient transplantation of neural stem cells into the injured spinal cord. Mol Brain 2:37. https://doi.org/10.1186/1756-6606-2-37CrossRefPubMedPubMedCentral

Orije J, Kara F, Guglielmetti C, Praet J, Van der Linden A, Ponsaerts P, Verhoye M (2015) Longitudinal monitoring of metabolic alterations in cuprizone mouse model of multiple sclerosis using 1H-magnetic resonance spectroscopy. Neuroimage 114:128–135. https://doi.org/10.1016/j.neuroimage.2015.04.012CrossRefPubMed

Roelants-Van RA, van der Grond J, de Vries LS, Groenendaal F (2001) Value of (1)H-MRS using different echo times in neonates with cerebral hypoxia-ischemia. Pediatr Res 49:356–362. https://doi.org/10.1203/00006450-200103000-00009CrossRef

Saito S, Takahashi Y, Ohki A, Shintani Y, Higuchi T (2019) Early detection of elevated lactate levels in a mitochondrial disease model using chemical exchange saturation transfer (CEST) and magnetic resonance spectroscopy (MRS) at 7T-MRI. Radiol Phys Technol 12:46–54. https://doi.org/10.1007/s12194-018-0490-1CrossRefPubMed

Sanz-Cortes M, Figueras F, Bargallo N, Padilla N, Amat-Roldan I, Gratacos E (2010) Abnormal brain microstructure and metabolism in small-for-gestational-age term fetuses with normal umbilical artery Doppler. Ultrasound Obstet Gynecol 36:159–165. https://doi.org/10.1002/uog.7724CrossRefPubMed

Sanz-Cortes M, Egana-Ugrinovic G, Zupan R, Figueras F, Gratacos E (2014) Brainstem and cerebellar differences and their association with neurobehavior in term small-for-gestational-age fetuses assessed by fetal MRI. Am J Obstet Gynecol 210:451–452. https://doi.org/10.1016/j.ajog.2013.12.008CrossRef

Sanz-Cortes M, Simoes RV, Bargallo N, Masoller N, Figueras F, Gratacos E (2015) Proton magnetic resonance spectroscopy assessment of fetal brain metabolism in late-onset 'small for gestational age' versus 'intrauterine growth restriction' fetuses. Fetal Diagn Ther 37:108–116. https://doi.org/10.1159/000365102CrossRefPubMed

Simoes RV, Munoz-Moreno E, Carbajo RJ, Gonzalez-Tendero A, Illa M, Sanz-Cortes M, Pineda-Lucena A, Gratacos E (2015) In vivo detection of perinatal brain metabolite changes in a rabbit model of intrauterine growth restriction (IUGR). PLoS ONE 10:e131310. https://doi.org/10.1371/journal.pone.0131310CrossRef

Simoes RV, Munoz-Moreno E, Cruz-Lemini M, Eixarch E, Bargallo N, Sanz-Cortes M, Gratacos E (2017) Brain metabolite alterations in infants born preterm with intrauterine growth restriction: association with structural changes and neurodevelopmental outcome. Am J Obstet Gynecol 216:61–62. https://doi.org/10.1016/j.ajog.2016.09.089CrossRef

Sizonenko SV, Camm EJ, Dayer A, Kiss JZ (2008) Glial responses to neonatal hypoxic-ischemic injury in the rat cerebral cortex. Int J Dev Neurosci 26:37–45. https://doi.org/10.1016/j.ijdevneu.2007.08.014CrossRefPubMed

Starcevic M, Predojevic M, Butorac D, Tumbri J, Konjevoda P, Kadic AS (2016) Early functional and morphological brain disturbances in late-onset intrauterine growth restriction. Early Hum Dev 93:33–38. https://doi.org/10.1016/j.earlhumdev.2015.12.001CrossRefPubMed

Story L, Damodaram MS, Allsop JM, McGuinness A, Patel A, Wylezinska M, Hagberg H, Kumar S, Rutherford MA (2011) Brain metabolism in fetal intrauterine growth restriction: a proton magnetic resonance spectroscopy study. Am J Obstet Gynecol 205:481–483. https://doi.org/10.1016/j.ajog.2011.06.032CrossRef

Swanson AM, David AL (2015) Animal models of fetal growth restriction: considerations for translational medicine. Placenta 36:623–630. https://doi.org/10.1016/j.placenta.2015.03.003CrossRefPubMed

Tolcos M, Bateman E, O'Dowd R, Markwick R, Vrijsen K, Rehn A, Rees S (2011) Intrauterine growth restriction affects the maturation of myelin. Exp Neurol 232:53–65. https://doi.org/10.1016/j.expneurol.2011.08.002CrossRefPubMed

Tolsa CB, Zimine S, Warfield SK, Freschi M, Sancho RA, Lazeyras F, Hanquinet S, Pfizenmaier M, Huppi PS (2004) Early alteration of structural and functional brain development in premature infants born with intrauterine growth restriction. Pediatr Res 56:132–138. https://doi.org/10.1203/01.PDR.0000128983.54614.7ECrossRefPubMed

Tronnes H, Wilcox AJ, Lie RT, Markestad T, Moster D (2014) Risk of cerebral palsy in relation to pregnancy disorders and preterm birth: a national cohort study. Dev Med Child Neurol 56:779–785. https://doi.org/10.1111/dmcn.12430CrossRefPubMedPubMedCentral

Ureyen I, Ozyuncu O, Sahin-Uysal N, Kara O, Basaran D, Turgal M, Deren O (2017) Relationship of maternal mean platelet volume with fetal Doppler parameters and neonatal complications in pregnancies with and without intrauterine growth restriction. J Matern Fetal Neonatal Med 30:471–474. https://doi.org/10.1080/14767058.2016.1175423CrossRefPubMed

van Batenburg-Eddes T, de Groot L, Steegers EA, Hofman A, Jaddoe VW, Verhulst FC, Tiemeier H (2010) Fetal programming of infant neuromotor development: the generation R study. Pediatr Res 67:132–137. https://doi.org/10.1203/PDR.0b013e3181c2dc76CrossRefPubMed

Verschuren MT, Morton JS, Abdalvand A, Mansour Y, Rueda-Clausen CF, Compston CA, Luyckx V, Davidge ST (2012) The effect of hypoxia-induced intrauterine growth restriction on renal artery function. J Dev Orig Health Dis 3:333–341. https://doi.org/10.1017/S2040174412000268CrossRefPubMed

Vielhaber S, Niessen HG, Debska-Vielhaber G, Kudin AP, Wellmer J, Kaufmann J, Schonfeld MA, Fendrich R, Willker W, Leibfritz D, Schramm J, Elger CE, Heinze HJ, Kunz WS (2008) Subfield-specific loss of hippocampal N-acetyl aspartate in temporal lobe epilepsy. Epilepsia 49:40–50. https://doi.org/10.1111/j.1528-1167.2007.01280.xCrossRefPubMed

Wang Y, Li XW, Liu J, Fu W (2018) Antenatal taurine supplementation in fetal rats with growth restriction improves neural stem cell proliferation by inhibiting the activities of rho family factors. J Matern Fetal Neonatal Med 31:1454–1461. https://doi.org/10.1080/14767058.2017.1319353CrossRefPubMed

Winterhager E, Gellhaus A (2017) Transplacental nutrient transport mechanisms of intrauterine growth restriction in rodent models and humans. Front Physiol 8:951. https://doi.org/10.3389/fphys.2017.00951CrossRefPubMedPubMedCentral

Title: Taurine supplementation improves hippocampal metabolism in immature rats with intrauterine growth restriction (IUGR) through protecting neurons and reducing gliosis
Authors: Qiong Fang
Jing Liu
Lang Chen
Qiaobin Chen
Yan Wang
Zuanfang Li
Wei Fu
Ying Liu
Publication date: 20-01-2022
Publisher: Springer US
Keyword: Intrauterine Growth Restriction
Published in: Metabolic Brain Disease / Issue 6/2022
Print ISSN: 0885-7490
Electronic ISSN: 1573-7365
DOI: https://doi.org/10.1007/s11011-021-00896-0

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Taurine supplementation improves hippocampal metabolism in immature rats with intrauterine growth restriction (IUGR) through protecting neurons and reducing gliosis

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 6/2022

PI3K/AKT/mTOR signalling inhibitor chrysophanol ameliorates neurobehavioural and neurochemical defects in propionic acid-induced experimental model of autism in adult rats

Putative involvement of sirtuin modulators in LPS-induced sickness behaviour in mice

Promising protein biomarkers in the early diagnosis of Alzheimer’s disease

Neuroprotective Effects of Theobromine in permanent bilateral common carotid artery occlusion rat model of cerebral hypoperfusion

Preventive effects of arctigenin from Arctium lappa L against LPS-induced neuroinflammation and cognitive impairments in mice

Exogenous hydrogen sulfide restores CSE and CBS but no 3-MST protein expression in the hypothalamus and brainstem after severe traumatic brain injury