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

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.

• Authors: 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
• Journal: Molecular neurobiology (Mol Neurobiol) Vol. 53 Issue 9 Pg. 5864-5875 (11 2016) ISSN: 1559-1182 [Electronic] United States
• PMID: 26497039 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• Glial Fibrillary Acidic Protein
• Reactive Oxygen Species
• S100 Proteins
• Malondialdehyde
• Electron Transport Complex IV
• Creatine Kinase
• Glutathione
• Melatonin
• Glycine

Topics

• Animals
• Animals, Newborn
• Antioxidants (metabolism)
• Cell Survival (drug effects)
• Cerebral Cortex (pathology)
• Corpus Callosum (metabolism)
• Creatine Kinase (metabolism)
• Electron Transport Complex IV (metabolism)
• Energy Metabolism (drug effects)
• Glial Fibrillary Acidic Protein (metabolism)
• Glutathione (metabolism)
• Glycine (administration & dosage)
• Homeostasis (drug effects)
• Injections, Intraventricular
• Lipid Peroxidation (drug effects)
• Malondialdehyde (metabolism)
• Melatonin (pharmacology)
• Neuroglia (drug effects, metabolism, pathology)
• Oxidation-Reduction
• Rats, Wistar
• Reactive Oxygen Species (metabolism)
• S100 Proteins (metabolism)