Quantitative distribution of monoamine oxidase A in brainstem monoamine nuclei is normal in major depression.
An abnormal expression of noradrenergic proteins (e.g., tyrosine hydroxylase, norepinephrine transporters) in the locus coeruleus has recently been demonstrated in subjects with major depression and/or victims of suicide. Monoamine oxidase A (MAO-A) is a key enzyme in the catabolism of biogenic amines and is expressed in brain noradrenergic neurons. In this study, the binding of [3H]Ro41-1049 to MAO-A was measured by quantitative autoradiography at multiple levels along the rostral-caudal axis of the noradrenergic locus coeruleus from subjects with major depression and age- and postmortem interval-matched control subjects who were psychiatrically normal. [3H]Ro41-1049 binding to MAO-A was unevenly distributed along the axis of the locus coeruleus, paralleling an uneven number of neuromelanin-containing (noradrenergic) neurons throughout the nucleus. Accordingly, there was a significant correlation between the number of neuromelanin-containing neurons per section and the specific binding of [3H]Ro41-1049 at any particular level of the locus coeruleus in control subjects (r(2)=0.25; p<0.001) and in subjects with major depression (r(2)=0.14; p<0. 001). Moderate levels of [3H]Ro41-1049 binding were observed in regions surrounding the locus coeruleus, including the central gray and the dorsal and median raphe nuclei. No significant differences in [3H]Ro41-1049 binding to MAO-A were observed at any level of the locus coeruleus, or raphe nuclei, comparing subjects with major depression to psychiatrically normal control subjects. These findings demonstrate that the pathophysiology of major depression is not likely to involve abnormalities in MAO-A.
Ordway
G A
GA
Department of Psychiatry, University of Mississippi Medical Center, Jackson, MS, USA. gordway@psychiatry.umsmed.edu
Farley
J T
JT
Dilley
G E
GE
Overholser
J C
JC
Meltzer
H Y
HY
Balraj
E K
EK
Stockmeier
C A
CA
Klimek
V
V
D000328:Adult; D000368:Aged; D015306:Biogenic Monoamines / Q000378:metabolism*; D001933:Brain Stem / Q000201:enzymology* / Q000473:pathology; D003866:Depressive Disorder / Q000378:metabolism*; D005260:Female; D006801:Humans; D008125:Locus Coeruleus / Q000201:enzymology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D011869:Radioligand Assay; D011903:Raphe Nuclei / Q000201:enzymology / Q000473:pathology; D013844:Thiazoles / Q000494:pharmacology
D015306:Biogenic Monoamines; D008996:Monoamine Oxidase Inhibitors; D013844:Thiazoles; C063456:Ro 41-1049; D008995:Monoamine Oxidase