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Published in: Metabolic Brain Disease 1/2018

01-02-2018 | Original Article

Neonatal hyperglycemia induces cell death in the rat brain

Authors: Andrea Pereira Rosa, Caroline Paula Mescka, Felipe Maciel Catarino, Alexandre Luz de Castro, Rayane Brinck Teixeira, Cristina Campos, Guilherme Baldo, Débora Dalmas Graf, Angela de Mattos-Dutra, Carlos Severo Dutra-Filho, Alex Sander da Rosa Araujo

Published in: Metabolic Brain Disease | Issue 1/2018

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Abstract

Several studies have examined neonatal diabetes, a rare disease characterized by hyperglycemia and low insulin levels that is usually diagnosed in the first 6 month of life. Recently, the effects of diabetes on the brain have received considerable attention. In addition, hyperglycemia may perturb brain function and might be associated with neuronal death in adult rats. However, few studies have investigated the damaging effects of neonatal hyperglycemia on the rat brain during central nervous system (CNS) development, particularly the mechanisms involved in the disease. Thus, in the present work, we investigated whether neonatal hyperglycemia induced by streptozotocin (STZ) promoted cell death and altered the levels of proteins involved in survival/death pathways in the rat brain. Cell death was assessed using FluoroJade C (FJC) staining and the expression of the p38 mitogen-activated protein kinase (p38), phosphorylated-c-Jun amino-terminal kinase (p-JNK), c-Jun amino-terminal kinase (JNK), protein kinase B (Akt), phosphorylated-protein kinase B (p-Akt), glycogen synthase kinase-3β (Gsk3β), B-cell lymphoma 2 (Bcl2) and Bcl2-associated X protein (Bax) protein were measured by Western blotting. The main results of this study showed that the metabolic alterations observed in diabetic rats (hyperglycemia and hypoinsulinemia) increased p38 expression and decreased p-Akt expression, suggesting that cell survival was altered and cell death was induced, which was confirmed by FJC staining. Therefore, the metabolic conditions observed during neonatal hyperglycemia may contribute to the harmful effect of diabetes on the CNS in a crucial phase of postnatal neuronal development.
Literature
go back to reference Ellerby LM, Ellerby HM, Park SM, Holleran AL, Murphy AN, Fiskum G, Kane DJ, Testa MP, Kayalar C, Bredesen DE (1996) Shift of the cellular oxidation-reduction potential in neural cells expressing Bcl-2. J Neurochem 67(3):1259–1267CrossRefPubMed Ellerby LM, Ellerby HM, Park SM, Holleran AL, Murphy AN, Fiskum G, Kane DJ, Testa MP, Kayalar C, Bredesen DE (1996) Shift of the cellular oxidation-reduction potential in neural cells expressing Bcl-2. J Neurochem 67(3):1259–1267CrossRefPubMed
go back to reference Flanagan SE, Patch AM, Mackay DJ, Edghill EL, Gloyn AL, Robinson D, Shield JP, Temple K, Ellard S, Hattersley AT (2007) Mutations in ATP-sensitive K+ channel genes cause transient neonatal diabetes and permanent diabetes in childhood or adulthood. Diabetes 56(7):1930–1937. https://doi.org/10.2337/db07-0043 CrossRefPubMed Flanagan SE, Patch AM, Mackay DJ, Edghill EL, Gloyn AL, Robinson D, Shield JP, Temple K, Ellard S, Hattersley AT (2007) Mutations in ATP-sensitive K+ channel genes cause transient neonatal diabetes and permanent diabetes in childhood or adulthood. Diabetes 56(7):1930–1937. https://​doi.​org/​10.​2337/​db07-0043 CrossRefPubMed
go back to reference Kermer P, Klöcker N, Labes M, Bähr M (2000) Insulin-like growth factor-I protects axotomized rat retinal ganglion cells from secondary death via PI3-K-dependent Akt phosphorylation and inhibition of caspase-3 in vivo. J Neurosci 20(2):2–8PubMed Kermer P, Klöcker N, Labes M, Bähr M (2000) Insulin-like growth factor-I protects axotomized rat retinal ganglion cells from secondary death via PI3-K-dependent Akt phosphorylation and inhibition of caspase-3 in vivo. J Neurosci 20(2):2–8PubMed
go back to reference Klein D, Kern RM, Sokol RZ (1995) A method for quantification and correction of proteins after transfer to immobilization membranes. Biochem Mol Biol Int 36(1):59–66PubMed Klein D, Kern RM, Sokol RZ (1995) A method for quantification and correction of proteins after transfer to immobilization membranes. Biochem Mol Biol Int 36(1):59–66PubMed
go back to reference Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193(1):265–275PubMed Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193(1):265–275PubMed
go back to reference Quinn L (2001) Type 2 diabetes: epidemiology, pathophysiology, and diagnosis. Nurs Clin North Am 36(2):175–192 vPubMed Quinn L (2001) Type 2 diabetes: epidemiology, pathophysiology, and diagnosis. Nurs Clin North Am 36(2):175–192 vPubMed
go back to reference Wu KJ, Chen YF, Tsai HY, Wu CR, Wood WG (2012) Guizhi-Fuling-wan, a traditional Chinese herbal medicine, ameliorates memory deficits and neuronal apoptosis in the Streptozotocin-induced hyperglycemic rodents via the decrease of Bax/Bcl2 ratio and Caspase-3 expression. Evid Based Complement Alternat Med 2012:656150–656111. https://doi.org/10.1155/2012/656150 PubMedCentralPubMed Wu KJ, Chen YF, Tsai HY, Wu CR, Wood WG (2012) Guizhi-Fuling-wan, a traditional Chinese herbal medicine, ameliorates memory deficits and neuronal apoptosis in the Streptozotocin-induced hyperglycemic rodents via the decrease of Bax/Bcl2 ratio and Caspase-3 expression. Evid Based Complement Alternat Med 2012:656150–656111. https://​doi.​org/​10.​1155/​2012/​656150 PubMedCentralPubMed
Metadata
Title
Neonatal hyperglycemia induces cell death in the rat brain
Authors
Andrea Pereira Rosa
Caroline Paula Mescka
Felipe Maciel Catarino
Alexandre Luz de Castro
Rayane Brinck Teixeira
Cristina Campos
Guilherme Baldo
Débora Dalmas Graf
Angela de Mattos-Dutra
Carlos Severo Dutra-Filho
Alex Sander da Rosa Araujo
Publication date
01-02-2018
Publisher
Springer US
Published in
Metabolic Brain Disease / Issue 1/2018
Print ISSN: 0885-7490
Electronic ISSN: 1573-7365
DOI
https://doi.org/10.1007/s11011-017-0170-6

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