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Glycine intracerebroventricular administration disrupts mitochondrial energy homeostasis in cerebral cortex and striatum of young rats.
- Source :
-
Neurotoxicity research [Neurotox Res] 2013 Nov; Vol. 24 (4), pp. 502-11. Date of Electronic Publication: 2013 May 03. - Publication Year :
- 2013
-
Abstract
- High tissue levels of glycine (GLY) are the biochemical hallmark of nonketotic hyperglycinemia (NKH), an inherited metabolic disease clinically characterized by severe neurological symptoms and brain abnormalities. Considering that the mechanisms underlying the neuropathology of this disease are not fully established, the present work investigated the in vivo effects of intracerebroventricular administration of GLY on important parameters of energy metabolism in cerebral cortex and striatum from young rats. Our results show that GLY reduced CO₂ production using glucose as substrate and inhibited the activities of citrate synthase and isocitrate dehydrogenase in striatum, whereas no alterations of these parameters were verified in cerebral cortex 30 min after GLY injection. We also observed that GLY diminished the activities of complex IV in cerebral cortex and complex I-III in striatum at 30 min and inhibited complex I-III activity in striatum at 24 h after its injection. Furthermore, GLY reduced the activity of total and mitochondrial creatine kinase in both brain structures 30 min and 24 h after its administration. In contrast, the activity of Na⁺, K⁺-ATPase was not altered by GLY. Finally, the antioxidants N-acetylcysteine and creatine, and the NMDA receptor antagonist MK-801 attenuated or fully prevented the inhibitory effects of GLY on creatine kinase and respiratory complexes in cerebral cortex and striatum. Our data indicate that crucial pathways for energy production and intracellular energy transfer are severely compromised by GLY. It is proposed that bioenergetic impairment induced by GLY in vivo may contribute to the neurological dysfunction found in patients affected by NKH.
- Subjects :
- Animals
Carbon Dioxide metabolism
Cerebral Cortex drug effects
Cerebral Cortex enzymology
Corpus Striatum drug effects
Corpus Striatum enzymology
Glycine administration & dosage
Homeostasis drug effects
Infusions, Intraventricular
Mitochondria drug effects
Mitochondria enzymology
Rats
Rats, Wistar
Cerebral Cortex metabolism
Corpus Striatum metabolism
Energy Metabolism drug effects
Glycine pharmacology
Mitochondria metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1476-3524
- Volume :
- 24
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Neurotoxicity research
- Publication Type :
- Academic Journal
- Accession number :
- 23640702
- Full Text :
- https://doi.org/10.1007/s12640-013-9396-1