Skip to main content

Advertisement

SpringerLink
Log in

Intracerebral Glycine Administration Impairs Energy and Redox Homeostasis and Induces Glial Reactivity in Cerebral Cortex of Newborn Rats

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Accumulation of glycine (GLY) is the biochemical hallmark of glycine encephalopathy (GE), an aminoacidopathy characterized by severe neurological dysfunction that may lead to early death. In the present study, we evaluated the effect of a single intracerebroventricular administration of GLY on bioenergetics, redox homeostasis, and histopathology in brain of neonatal rats. Our results demonstrated that GLY decreased the activities of the respiratory chain complex IV and creatine kinase, induced reactive species generation, and diminished glutathione (GSH) levels 1, 5, and 10 days after GLY injection in cerebral cortex of 1-day-old rats. GLY also increased malondialdehyde (MDA) levels 5 days after GLY infusion in this brain region. Furthermore, GLY differentially modulated the activities of superoxide dismutase, catalase, and glutathione peroxidase depending on the period tested after GLY administration. In contrast, bioenergetics and redox parameters were not altered in brain of 5-day-old rats. Regarding the histopathological analysis, GLY increased S100β staining in cerebral cortex and striatum, and GFAP in corpus callosum of 1-day-old rats 5 days after injection. Finally, we verified that melatonin prevented the decrease of complex IV and CK activities and GSH concentrations, and the increase of MDA levels and S100β staining caused by GLY. Based on our findings, it may be presumed that impairment of redox and energy homeostasis and glial reactivity induced by GLY may contribute to the neurological dysfunction observed in GE.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

References

  1. Hamosh A, Johnston MV (2001) Non-ketotic hyperglycinemia. In: Scriver CR, Beaudet A, Sly WS, Valle D (eds) The metabolic and molecular bases of inherited disease, vol Editors, 8th edn. McGraw-Hill, New York, pp 2065–2078

    Google Scholar 

  2. Applegarth DA, Toone JR, Lowry RB (2000) Incidence of inborn errors of metabolism in British Columbia, 1969–1996. Pediatrics 105(1):e10

    Article  CAS  PubMed  Google Scholar 

  3. Heindel W, Kugel H, Roth B (1993) Noninvasive detection of increased glycine content by proton MR spectroscopy in the brains of two infants with nonketotic hyperglycinemia. Am J Neuroradiol 14(3):629–635

    CAS  PubMed  Google Scholar 

  4. Raghavendra S, Ashalatha R, Thomas SV, Kesavadas C (2007) Focal neuronal loss, reversible subcortical focal T2 hypointensity in seizures with a nonketotic hyperglycemic hyperosmolar state. Neuroradiology 49(4):299–305. doi:10.1007/s00234-006-0189-6

    Article  CAS  PubMed  Google Scholar 

  5. Shuman RM, Leech RW, Scott CR (1978) The neuropathology of the nonketotic and ketotic hyperglycinemias: three cases. Neurology 28(2):139–146

    Article  CAS  PubMed  Google Scholar 

  6. Bekiesiniska-Figatowska M, Rokicki D, Walecki J (2001) MRI in nonketotic hyperglycinaemia: case report. Neuroradiology 43(9):792–793

    Article  CAS  PubMed  Google Scholar 

  7. Hennermann JB, Berger JM, Grieben U, Scharer G, Van Hove JL (2012) Prediction of long-term outcome in glycine encephalopathy: a clinical survey. J Inherit Metab Dis 35(2):253–261. doi:10.1007/s10545-011-9398-1

    Article  CAS  PubMed  Google Scholar 

  8. Tsuyusaki Y, Shimbo H, Wada T, Iai M, Tsuji M, Yamashita S, Aida N, Kure S, Osaka H (2012) Paradoxical increase in seizure frequency with valproate in nonketotic hyperglycinemia. Brain Dev 34(1):72–75. doi:10.1016/j.braindev.2011.01.005

    Article  PubMed  Google Scholar 

  9. Hara H, Sukamoto T, Kogure K (1993) Mechanism and pathogenesis of ischemia-induced neuronal damage. Prog Neurobiol 40(6):645–670. doi:10.1016/0301-0082(93)90009-H

    Article  CAS  PubMed  Google Scholar 

  10. Kure S, Tada K, Narisawa K (1997) Nonketotic hyperglycinemia: biochemical, molecular, and neurological aspects. Jpn J Hum Genet 42(1):13–22. doi:10.1007/BF02766917

    Article  CAS  PubMed  Google Scholar 

  11. Applegarth DA, Toone JR (2001) Nonketotic hyperglycinemia (glycine encephalopathy): laboratory diagnosis. Mol Genet Metab 74(1–2):139–146. doi:10.1006/mgme.2001.3224

    Article  CAS  PubMed  Google Scholar 

  12. Kono Y, Shigetomi E, Inoue K, Kato F (2007) Facilitation of spontaneous glycine release by anoxia potentiates NMDA receptor current in the hypoglossal motor neurons of the rat. Eur J Neurosci 25(6):1748–1756. doi:10.1111/j.1460-9568.2007.05426.x

    Article  PubMed  Google Scholar 

  13. Katsuki H, Watanabe Y, Fujimoto S, Kume T, Akaike A (2007) Contribution of endogenous glycine and d-serine to excitotoxic and ischemic cell death in rat cerebrocortical slice cultures. Life Sci 81(9):740–749. doi:10.1016/j.lfs.2007.07.001

    Article  CAS  PubMed  Google Scholar 

  14. Leipnitz G, Solano AF, Seminotti B, Amaral AU, Fernandes CG, Beskow AP, Dutra Filho CS, Wajner M (2009) Glycine provokes lipid oxidative damage and reduces the antioxidant defenses in brain cortex of young rats. Cell Mol Neurobiol 29(2):253–261. doi:10.1007/s10571-008-9318-6

    Article  CAS  PubMed  Google Scholar 

  15. Busanello EN, Moura AP, Viegas CM, Zanatta A, da Costa FG, Schuck PF, Wajner M (2010) Neurochemical evidence that glycine induces bioenergetical dysfunction. Neurochem Int 56(8):948–954. doi:10.1016/j.neuint.2010.04.002

    Article  CAS  PubMed  Google Scholar 

  16. Seminotti B, Knebel LA, Fernandes CG, Amaral AU, da Rosa MS, Eichler P, Leipnitz G, Wajner M (2011) Glycine intrastriatal administration induces lipid and protein oxidative damage and alters the enzymatic antioxidant defenses in rat brain. Life Sci 89(7–8):276–281. doi:10.1016/j.lfs.2011.06.013

    Article  CAS  PubMed  Google Scholar 

  17. Pai YJ, Leung KY, Savery D, Hutchin T, Prunty H, Heales S, Brosnan ME, Brosnan JT, Copp AJ, Greene ND (2015) Glycine decarboxylase deficiency causes neural tube defects and features of non-ketotic hyperglycinemia in mice. Nat Commun 6:6388. doi:10.1038/ncomms7388

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Olivera-Bravo S, Fernandez A, Sarlabos MN, Rosillo JC, Casanova G, Jimenez M, Barbeito L (2011) Neonatal astrocyte damage is sufficient to trigger progressive striatal degeneration in a rat model of glutaric acidemia-I. PLoS One 6(6):e20831. doi:10.1371/journal.pone.0020831

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Olivera-Bravo S, Isasi E, Fernandez A, Rosillo JC, Jimenez M, Casanova G, Sarlabos MN, Barbeito L (2014) White matter injury induced by perinatal exposure to glutaric acid. Neurotox Res 25(4):381–391. doi:10.1007/s12640-013-9445-9

    Article  CAS  PubMed  Google Scholar 

  20. Olivier P, Fontaine RH, Loron G, Van Steenwinckel J, Biran V, Massonneau V, Kaindl A, Dalous J, Charriaut-Marlangue C, Aigrot MS, Pansiot J, Verney C, Gressens P, Baud O (2009) Melatonin promotes oligodendroglial maturation of injured white matter in neonatal rats. PLoS One 4(9):e7128. doi:10.1371/journal.pone.0007128

    Article  PubMed  PubMed Central  Google Scholar 

  21. Evelson P, Travacio M, Repetto M, Escobar J, Llesuy S, Lissi EA (2001) Evaluation of total reactive antioxidant potential (TRAP) of tissue homogenates and their cytosols. Arch Biochem Biophys 388(2):261–266. doi:10.1006/abbi.2001.2292

    Article  CAS  PubMed  Google Scholar 

  22. Schapira AHV, Mann VM, Cooper JM, Dexter D, Daniel SE, Jenner P, Clark JB, Marsden CD (1990) Anatomic and disease specificity of NADH CoQ1 reductase (complex I) deficiency in Parkinson’s disease. J Neurochem 55(6):2142–2145

    Article  CAS  PubMed  Google Scholar 

  23. Fischer JC, Ruitenbeek W, Berden JA, Trijbels JM, Veerkamp JH, Stadhouders AM, Sengers RC, Janssen AJ (1985) Differential investigation of the capacity of succinate oxidation in human skeletal muscle. Clin Chim Acta 153(1):23–36

    Article  CAS  PubMed  Google Scholar 

  24. Rustin P, Chretien D, Bourgeron T, Gerard B, Rotig A, Saudubray JM, Munnich A (1994) Biochemical and molecular investigations in respiratory chain deficiencies. Clin Chim Acta 228(1):35–51

    Article  CAS  PubMed  Google Scholar 

  25. da Silva CG, Ribeiro CAJ, Leipnitz G, Dutra CS, Wyse ATS, Wannmacher CMD, Sarkis JJF, Jakobs C, Wajner M (2002) Inhibition of cytochrome c oxidase activity in rat cerebral cortex and human skeletal muscle by d-2-hydroxyglutaric acid in vitro. Biochim Biophys Acta 1586(1):81–91. doi:10.1016/S09254439(01)00088-6

    Article  PubMed  Google Scholar 

  26. Hughes BP (1962) A method for estimation of serum creatine kinase and its use in comparing creatine kinase and aldolase activity in normal and pathological sera. Clin Chim Acta 7(5):597–603

    Article  CAS  PubMed  Google Scholar 

  27. da Silva CG, Bueno ARF, Schuck PF, Leipnitz G, Ribeiro CAJ, Rosa RB, Dutra CS, Wyse ATS, Wannmacher CMD, Wajner M (2004) Inhibition of creatine kinase activity from rat cerebral cortex by d-2-hydroxyglutaric acid in vitro. Neurochem Int 44(1):45–52. doi:10.1016/S0197-0186(03)00098-6

    Article  PubMed  Google Scholar 

  28. Yagi K (1998) Simple procedure for specific assay of lipid hydroperoxides in serum or plasma. Methods Mol Biol 108:107–110. doi:10.1385/0-89603-472-0:107

    CAS  PubMed  Google Scholar 

  29. LeBel CP, Ischiropoulos H, Bondy SC (1992) Evaluation of the probe 2′,7′-dichlorofluorescin as an indicator of reactive oxygen species formation and oxidative stress. Chem Res Toxicol 5(2):227–231

    Article  CAS  PubMed  Google Scholar 

  30. Browne RW, Armstrong D (1998) Reduced glutathione and glutathione disulfide. Methods Mol Biol 108:347–352. doi:10.1385/0-89603-472-0:347

    CAS  PubMed  Google Scholar 

  31. Marklund SL (1985) Product of extracellular-superoxide dismutase catalysis. FEBS Lett 184(2):237–239

    Article  CAS  PubMed  Google Scholar 

  32. Aebi H (1984) Catalase in vitro. Methods Enzymol 105:121–126

    Article  CAS  PubMed  Google Scholar 

  33. Wendel A (1981) Glutathione peroxidase. Methods Enzymol 77:325–333

    Article  CAS  PubMed  Google Scholar 

  34. Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65(1–2):55–63

    Article  CAS  PubMed  Google Scholar 

  35. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193(1):265–275

    CAS  PubMed  Google Scholar 

  36. Brun A, Borjeson M, Hultberg B, Sjoblad S, Akesson H, Litwin E (1979) Neonatal non-ketotic hyperglycinemia: a clinical, biochemical and neuropathological study including electronmicroscopic findings. Neuropadiatrie 10(2):195–205. doi:10.1055/s-0028-1085325

    Article  CAS  PubMed  Google Scholar 

  37. Korman SH, Wexler ID, Gutman A, Rolland MO, Kanno J, Kure S (2006) Treatment from birth of nonketotic hyperglycinemia due to a novel GLDC mutation. Ann Neurol 59(2):411–415. doi:10.1002/ana.20759

    Article  CAS  PubMed  Google Scholar 

  38. Halliwell B, Gutteridge JMC (2007) Measurement of reactive species. Free radicals in biology and medicine, 4th edn. Oxford University Press, Oxford

    Google Scholar 

  39. Moura AP, Grings M, Marcowich GF, Bumbel AP, Parmeggiani B, de Moura Alvorcem L, Wajner M, Leipnitz G (2014) Evidence that glycine induces lipid peroxidation and decreases glutathione concentrations in rat cerebellum. Mol Cell Biochem 395(1–2):125–134. doi:10.1007/s11010-014-2118-z

    Article  CAS  PubMed  Google Scholar 

  40. Reiter RJ, Tan DX, Rosales-Corral S, Manchester LC (2013) The universal nature, unequal distribution and antioxidant functions of melatonin and its derivatives. Mini Rev Med Chem 13(3):373–384. doi:10.2174/1389557511313030006

    CAS  PubMed  Google Scholar 

  41. Bromme HJ, Morke W, Peschke D, Ebelt H (2000) Scavenging effect of melatonin on hydroxyl radicals generated by alloxan. J Pineal Res 29(4):201–208. doi:10.1034/j.1600-0633.2002.290402.x

    Article  CAS  PubMed  Google Scholar 

  42. Matuszak Z, Reszka K, Chignell CF (1997) Reaction of melatonin and related indoles with hydroxyl radicals: EPR and spin trapping investigations. Free Radic Biol Med 23(3):367–372. doi:10.1016/S0891-5849(96)00614-4

    Article  CAS  PubMed  Google Scholar 

  43. Stasica P, Ulanski P, Rosiak JM (1998) Melatonin as a hydroxyl radical scavenger. J Pineal Res 25(1):65–66

    Article  CAS  PubMed  Google Scholar 

  44. Reyes-Toso CF, Rebagliati IR, Ricci CR, Linares LM, Albornoz LE, Cardinali DP, Zaninovich A (2006) Effect of melatonin treatment on oxygen consumption by rat liver mitochondria. Amino Acids 31(3):299–302. doi:10.1007/s00726-005-0280-z

    Article  CAS  PubMed  Google Scholar 

  45. Garcia JJ, Lopez-Pingarron L, Almeida-Souza P, Tres A, Escudero P, Garcia-Gil FA, Tan DX, Reiter RJ, Ramirez JM, Bernal-Perez M (2014) Protective effects of melatonin in reducing oxidative stress and in preserving the fluidity of biological membranes: a review. J Pineal Res 56(3):225–237. doi:10.1111/jpi.12128

    Article  CAS  PubMed  Google Scholar 

  46. Martin M, Macias M, Escames G, Reiter RJ, Agapito MT, Ortiz GG, Acuna-Castroviejo D (2000) Melatonin-induced increased activity of the respiratory chain complexes I and IV can prevent mitochondrial damage induced by ruthenium red in vivo. J Pineal Res 28(4):242–248. doi:10.1034/j.1600-079X.2000.280407.x

    Article  CAS  PubMed  Google Scholar 

  47. Gan L, Johnson JA (2014) Oxidative damage and the Nrf2-ARE pathway in neurodegenerative diseases. Biochim Biophys Acta 1842(8):1208–1218. doi:10.1016/j.bbadis.2013.12.011

    Article  CAS  PubMed  Google Scholar 

  48. Itoh K, Ishii T, Wakabayashi N, Yamamoto M (1999) Regulatory mechanisms of cellular response to oxidative stress. Free Radic Res 31(4):319–324

    Article  CAS  PubMed  Google Scholar 

  49. Johnson JA, Johnson DA, Kraft AD, Calkins MJ, Jakel RJ, Vargas MR, Chen PC (2008) The Nrf2-ARE pathway: an indicator and modulator of oxidative stress in neurodegeneration. Ann N Y Acad Sci 1147:61–69. doi:10.1196/annals.1427.036

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Shih AY, Johnson DA, Wong G, Kraft AD, Jiang L, Erb H, Johnson JA, Murphy TH (2003) Coordinate regulation of glutathione biosynthesis and release by Nrf2-expressing glia potently protects neurons from oxidative stress. J Neurosci 23(8):3394–3406

    CAS  PubMed  Google Scholar 

  51. Limon-Pacheco JH, Gonsebatt ME (2010) The glutathione system and its regulation by neurohormone melatonin in the central nervous system. Cent Nerv Syst Agents Med Chem 10(4):287–297. doi:10.2174/187152410793429683

    Article  CAS  PubMed  Google Scholar 

  52. Kaushik S, Kaur J (2003) Chronic cold exposure affects the antioxidant defense system in various rat tissues. Clin Chim Acta 333(1):69–77. doi:10.1016/S0009-8981(03)00171-2

    Article  CAS  PubMed  Google Scholar 

  53. Singh P, Jain A, Kaur G (2004) Impact of hypoglycemia and diabetes on CNS: correlation of mitochondrial oxidative stress with DNA damage. Mol Cell Biochem 260(1–2):153–159

    Article  CAS  PubMed  Google Scholar 

  54. Jafari M (2007) Dose- and time-dependent effects of sulfur mustard on antioxidant system in liver and brain of rat. Toxicology 231(1):30–39. doi:10.1016/j.tox.2006.11.048

    Article  CAS  PubMed  Google Scholar 

  55. Costa MZ, da Silva TM, Flores NP, Schmitz F, da Silva Scherer EB, Viau CM, Saffi J, Barschak AG, de Souza Wyse AT, Spanevello RM, Stefanello FM (2013) Methionine and methionine sulfoxide alter parameters of oxidative stress in the liver of young rats: in vitro and in vivo studies. Mol Cell Biochem 384(1–2):21–28. doi:10.1007/s11010-013-1777-5

    Article  CAS  PubMed  Google Scholar 

  56. da Rosa MS, Seminotti B, Amaral AU, Fernandes CG, Gasparotto J, Moreira JC, Gelain DP, Wajner M, Leipnitz G (2013) Redox homeostasis is compromised in vivo by the metabolites accumulating in 3-hydroxy-3-methylglutaryl-CoA lyase deficiency in rat cerebral cortex and liver. Free Radic Res 47(12):1066–1075. doi:10.3109/10715762.2013.853876

    Article  PubMed  Google Scholar 

  57. Sasso S, Dalmedico L, Delwing-Dal Magro D, Wyse AT, Delwing-de Lima D (2014) Effect of N-acetylarginine, a metabolite accumulated in hyperargininemia, on parameters of oxidative stress in rats: protective role of vitamins and l-NAME. Cell Biochem Funct 32(6):511–519. doi:10.1002/cbf.3045

    Article  CAS  PubMed  Google Scholar 

  58. Viegas CM, Zanatta A, Grings M, Hickmann FH, Monteiro WO, Soares LE, Sitta A, Leipnitz G, de Oliveira FH, Wajner M (2014) Disruption of redox homeostasis and brain damage caused in vivo by methylmalonic acid and ammonia in cerebral cortex and striatum of developing rats. Free Radic Res 48(6):659–669. doi:10.3109/10715762.2014.898842

    Article  CAS  PubMed  Google Scholar 

  59. Ferriero DM, Miller SP (2010) Imaging selective vulnerability in the developing nervous system. J Anat 217(4):429–435. doi:10.1111/j.1469-7580.2010.01226.x

    Article  PubMed  PubMed Central  Google Scholar 

  60. Ikonomidou C, Kaindl AM (2011) Neuronal death and oxidative stress in the developing brain. Antioxid Redox Signal 14(8):1535–1550. doi:10.1089/ars.2010.3581

    Article  CAS  PubMed  Google Scholar 

  61. Paupe A, Bidat L, Sonigo P, Lenclen R, Molho M, Ville Y (2002) Prenatal diagnosis of hypoplasia of the corpus callosum in association with non-ketotic hyperglycinemia. Ultrasound Obstet Gynecol 20(6):616–619. doi:10.1046/j.1469-0705.2002.00869

    Article  CAS  PubMed  Google Scholar 

  62. Press GA, Barshop BA, Haas RH, Nyhan WL, Glass RF, Hesselink JR (1989) Abnormalities of the brain in nonketotic hyperglycinemia: MR manifestations. AJNR Am J Neuroradiol 10(2):315–321

    CAS  PubMed  Google Scholar 

  63. del Toro M, Arranz JA, Macaya A, Riudor E, Raspall M, Moreno A, Vazquez E, Ortega A, Matsubara Y, Kure S, Roig M (2006) Progressive vacuolating glycine leukoencephalopathy with pulmonary hypertension. Ann Neurol 60(1):148–152. doi:10.1002/ana.20887

    Article  PubMed  Google Scholar 

  64. Sorci G, Bianchi R, Riuzzi F, Tubaro C, Arcuri C, Giambanco I, Donato R (2010). S100B protein, a damage-associated molecular pattern protein in the brain and heart, and beyond. Cardiovasc Psychiatry Neurol. doi:10.1155/2010/656481

  65. Cerutti SM, Chadi G (2000) S100 immunoreactivity is increased in reactive astrocytes of the visual pathways following a mechanical lesion of the rat occipital cortex. Cell Biol Int 24(1):35–49. doi:10.1006/cbir.1999.0451

    Article  CAS  PubMed  Google Scholar 

  66. Griffin WS, Sheng JG, Mrak RE (1998) Senescence-accelerated overexpression of S100beta in brain of SAMP6 mice. Neurobiol Aging 19(1):71–76

    Article  CAS  PubMed  Google Scholar 

  67. Celikbilek A, Akyol L, Sabah S, Tanik N, Adam M, Celikbilek M, Korkmaz M, Yilmaz N (2014) S100B as a glial cell marker in diabetic peripheral neuropathy. Neurosci Lett 558:53–57. doi:10.1016/j.neulet.2013.10.067

    Article  CAS  PubMed  Google Scholar 

  68. Avishai-Eliner S, Brunson KL, Sandman CA, Baram TZ (2002) Stressed-out, or in (utero)? Trends Neurosci 25(10):518–524

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Rice D, Barone S Jr (2000) Critical periods of vulnerability for the developing nervous system: evidence from humans and animal models. Environ Health Perspect 108(Suppl 3):511–533

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

The authors declare that there is no conflict of interest. This work was supported by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Programa de Apoio a Núcleos de Excelência (PRONEX II), Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS), Pró-Reitoria de Pesquisa/Universidade Federal do Rio Grande do Sul (PROPESQ/UFRGS), Financiadora de estudos e projetos (FINEP), Rede Instituto Brasileiro de Neurociência (IBN-Net) no. 01.06.0842-00, and Instituto Nacional de Ciência e Tecnologia em Excitotoxicidade e Neuroproteção (INCT-EN).

Author information

Authors and Affiliations

  1. Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos No. 2600, 90035-003, Porto Alegre, RS, Brazil

    Alana Pimentel Moura, Belisa Parmeggiani, Mateus Grings, Leonardo de Moura Alvorcem, Rafael Mello Boldrini, Anna Paula Bumbel, Marcela Moreira Motta, Bianca Seminotti, Moacir Wajner & Guilhian Leipnitz

  2. Serviço de Genética Médica do Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil

    Moacir Wajner

Authors
  1. Alana Pimentel Moura
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Belisa Parmeggiani
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mateus Grings
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Leonardo de Moura Alvorcem
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rafael Mello Boldrini
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Anna Paula Bumbel
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Marcela Moreira Motta
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Bianca Seminotti
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Moacir Wajner
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Guilhian Leipnitz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Guilhian Leipnitz.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Moura, A.P., Parmeggiani, B., Grings, M. et al. Intracerebral Glycine Administration Impairs Energy and Redox Homeostasis and Induces Glial Reactivity in Cerebral Cortex of Newborn Rats. Mol Neurobiol 53, 5864–5875 (2016). https://doi.org/10.1007/s12035-015-9493-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12035-015-9493-7

Keywords

Search

Navigation