Format

Send to

Choose Destination
Exp Neurol. 2016 Apr;278:4-10. doi: 10.1016/j.expneurol.2016.01.019. Epub 2016 Jan 26.

Treatment with the MAO-A inhibitor clorgyline elevates monoamine neurotransmitter levels and improves affective phenotypes in a mouse model of Huntington disease.

Author information

1
Translational Laboratory in Genetic Medicine (TLGM), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos, Level 5, Singapore 138648.
2
Cardiovascular Research Institute, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
3
Translational Laboratory in Genetic Medicine (TLGM), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos, Level 5, Singapore 138648; Cardiovascular Research Institute, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
4
Translational Laboratory in Genetic Medicine (TLGM), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos, Level 5, Singapore 138648; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 117597, Singapore; Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, BC V5Z 4H4, Canada.
5
Translational Laboratory in Genetic Medicine (TLGM), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos, Level 5, Singapore 138648; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 117597, Singapore. Electronic address: pouladi@tlgm.a-star.edu.sg.

Abstract

Abnormal monoamine oxidase A and B (MAO-A/B) activity and an imbalance in monoamine neurotransmitters have been suggested to underlie the pathobiology of depression, a major psychiatric symptom observed in patients with neurodegenerative diseases, such as Huntington disease (HD). Increased MAO-A/B activity has been observed in brain tissue from patients with HD and in human and rodent HD neural cells. Using the YAC128 mouse model of HD, we studied the effect of an irreversible MAO-A inhibitor, clorgyline, on the levels of select monoamine neurotransmitters associated with affective function. We observed a decrease in striatal levels of the MAO-A/B substrates, dopamine and norepinephrine, in YAC128 HD mice compared with wild-type mice, which was accompanied by increased anxiety- and depressive-like behaviour at five months of age. Treatment for 26 days with clorgyline restored dopamine, serotonin, and norepinephrine neurotransmitter levels in the striatum and reduced anxiety- and depressive-like behaviour in YAC128 HD mice. This study supports a potential therapeutic use for MAO-A inhibitors in the treatment of depression and anxiety in patients with HD.

KEYWORDS:

Anxiety; Depression; Huntington's disease; Monoamine oxidase; Monoamine oxidase inhibitors; Monoamines; Mouse model; Psychiatric features

PMID:
26825854
DOI:
10.1016/j.expneurol.2016.01.019
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center