Excitotoxic neuronal injury in chronic homocysteine neurotoxicity studied in vitro: The role of NMDA and group I metabotropic glutamate receptors

• Authors: E. Zieminska , J.W. Lazarewicz
• Languages of publication: EN

Abstracts

EN

Elevated homocysteine is a risk factor in cardiovascular diseases and neurodegeneration. Among the putative mechanisms of homocysteine-evoked neurotoxicity, disturbances in methylation processes and NMDA receptor-mediated excitotoxicity have been suggested. Our previous studies demonstrated that group I metabotropic glutamate receptors along with NMDA receptors participate in acute homocysteine-induced neuronal damage. In this study, using propidium iodide staining, we tested whether the same mechanism may mediate chronic homocysteine neurotoxicity. Our results confirmed that the application of D,L-homocysteine in micromolar concentrations for 3 days induces neurodegeneration in primary cultures of cerebellar granule neurons. Uncompetitive NMDA receptor antagonist MK-801, and mGlu1 or mGlu5 receptor antagonists (LY367385 and MPEP, respectively), given alone provided very limited neuroprotection. However, simultaneous application of the NMDA receptor antagonists MK-801, memantine or amantadine and MPEP almost completely prevented chronic homocysteine neurotoxicity. These findings suggest a novel therapeutic strategy to combat neurodegeneration induced by hyperhomocysteinemia comprising a combination of antagonists of group I metabotropic glutamate receptors and NMDA receptors.

Keywords

EN

EXCITOTOXICITY; HOMOCYSTEINE; NEURONAL INJURY; NEUROPROTECTION; NEUROTOXICITY

Discipline

• EXPERIMENTAL_BIOLOGY_&_MEDICINE: EXPERIMENTAL BIOLOGY & MEDICINE

• Publisher: Marceli Nencki Institute of Experimental Biology, Polish Academy of Sciences
• Journal: Acta Neurobiologiae Experimentalis
• Year: 2006
• Volume: 66
• Issue: 4
• Pages: 301-309

Contributors

author

E. Zieminska

author

J.W. Lazarewicz

• Document Type: ARTICLE
• Publication order reference: Jerzy W. Lazarewicz, Department of Neurochemistry, Medical Research Centre, Polish Academy of Sciences, 5 Pawinskiego Street, 02-106 Warsaw, Poland