Distribution of Monoamine Oxidase Proteins in Human Brain: Implications for Brain Imaging Studies

Journal of Cerebral Blood Flow and Metabolism - Tập 33 Số 6 - Trang 863-871 - 2013
Junchao Tong1,2, Jeffrey H. Meyer3, Yoshiaki Furukawa4, Isabelle Boileau1, Li‐Jan Chang2, Alan A. Wilson5, Sylvain Houle1
1Addiction Imaging Research Group, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
2Human Brain Laboratory, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
3Mood and Anxiety Division, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
4Department of Neurology, Juntendo Tokyo Koto Geriatric Medical Center, and Faculty of Medicine, University & Post Graduate University of Juntendo, Tokyo, Japan
5Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada

Tóm tắt

Positron emission tomography (PET) imaging of monoamine oxidases (MAO-A: [11C]harmine, [11C]clorgyline, and [11C]befloxatone; MAO-B: [11C]deprenyl-D2) has been actively pursued given clinical importance of MAOs in human neuropsychiatric disorders. However, it is unknown how well PET outcome measures for the different radiotracers are quantitatively related to actual MAO protein levels. We measured regional distribution ( n = 38) and developmental/aging changes (21 hours to 99 years) of both MAOs by quantitative immunoblotting in autopsied normal human brain. MAO-A was more abundant than MAO-B in infants, which was reversed as MAO-B levels increased faster before 1 year and, unlike MAO-A, kept increasing steadily to senescence. In adults, regional protein levels of both MAOs were positively and proportionally correlated with literature postmortem data of MAO activities and binding densities. With the exception of [11C]befloxatone (binding potential (BP), r = 0.61, P = 0.15), correlations between regional PET outcome measures of binding in the literature and MAO protein levels were good ( P < 0.01) for [11C]harmine (distribution volume, r = 0.86), [11C]clorgyline (λk3, r = 0.82), and [11C]deprenyl-D2 (λk3 or modified Patlak slope, r = 0.78 to 0.87), supporting validity of the latter imaging measures. However, compared with in vitro data, the latter PET measures underestimated regional contrast by ~2-fold. Further studies are needed to address cause of the in vivo vs. in vitro nonproportionality.

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Thông tin xuất bản

Journal of Cerebral Blood Flow and Metabolism

Tập 33 Số 6

863-871

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