Neonatal hyperglycemia induces cell death in the rat brain.

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.

• 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
• Journal: Metabolic brain disease (Metab Brain Dis) Vol. 33 Issue 1 Pg. 333-342 (02 2018) ISSN: 1573-7365 [Electronic] United States
• PMID: 29260360 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• bcl-2-Associated X Protein
• Mitogen-Activated Protein Kinases

Topics

• Animals
• Brain (metabolism, pathology)
• Cell Death (physiology)
• Diabetes Mellitus, Experimental (metabolism, pathology)
• Female
• Hyperglycemia (metabolism)
• MAP Kinase Signaling System (physiology)
• Male
• Mitogen-Activated Protein Kinases (metabolism)
• Neurons (metabolism)
• Phosphorylation
• Rats, Wistar
• bcl-2-Associated X Protein (metabolism)