Journal
BRAIN RESEARCH
Volume 1370, Issue -, Pages 204-214Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.brainres.2010.11.020
Keywords
Monoamine oxidase; Enzyme inhibitor; Ro 41-1049; Lazabemide; In vitro binding; Mapping; Neurodegeneration; Inflammatory response; Gliosis
Categories
Funding
- Health Research Council of New Zealand
- Neurological Foundation of New Zealand
Ask authors/readers for more resources
Huntington's disease (HD) is a rare genetic disease associated with the degeneration of GABAergic striatal projection neurons in the basal ganglia leading to movement disorders with behavioral symptoms for which there is presently no therapy. Abnormally high levels of monoamine oxidase (MAO) activity, which are potentially linked to cytotoxic free radical formation, are known to occur during aging and in neurodegenerative disorders (MAO-B is markedly increased in plaque-associated astrocytes in Alzheimer's disease). We therefore measured, with anatomical resolution, MAO-A and -B activities in 5 cases of HD (severity grades 1-3) and age-matched controls by quantitative enzyme radioautography using radiolabeled enzyme inhibitors H-3-Ro 41-1049 and H-3-lazabemide, respectively, as high-affinity ligands in vitro. MAO-A was increased significantly (ca. 50%; p < 0.01) in the putamen and substantia nigra pars compacta of the basal ganglia and in the pons. Higher increases in MAO-B (75%-200%; p < 0.01) occurred in the putamen, ventral striatum, globus pallidus externus and internus of the basal ganglia and in the insular cortex. The increased enzyme levels (especially of MAO-B) seemed to correlate with the grade of disease severity. We conclude that MAO increases in those regions of HD brains which are known to undergo neurodegeneration accompanied by glioses. Whether or not this increased enzyme activity is a cause or effect of the resulting loss of the GABAergic projection neurons in HD is yet to be clarified. Moreover, it remains to be seen if selective enzyme inhibitors have therapeutic utility in the treatment of HD by reducing oxidative stress locally. (C) 2010 Elsevier B.V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available