Search results

Search:
in the keywords: NEURONAL INJURY

Sort By:

Limit search:

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

100%

Zieminska E., Lazarewicz J. W.

Acta Neurobiologiae Experimentalis

2006

vol. 66

issue 4

301-309

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.

Refine search results

1 Acta Neurobiologiae Experimentalis

1 2006

1 Lazarewicz J. W.

1 Zieminska E.

Search results

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