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Increased Density of Catalytic Sites and Expression of Brain Monoamine Oxidase A in Humans with Hepatic Encephalopathy
Author(s) -
Mousseau D. D.,
Baker G. B.,
Butterworth R. F.
Publication year - 1997
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1997.68031200.x
Subject(s) - monoamine oxidase , monoamine neurotransmitter , biogenic amine , pathophysiology , monoamine oxidase a , hepatic encephalopathy , medicine , mania , endocrinology , biology , biochemistry , central nervous system , enzyme , serotonin , neurotransmitter , receptor , bipolar disorder , cirrhosis , lithium (medication)
Altered biogenic amine metabolism and function are believed to underlie certain of the neuropsychiatric symptoms, e.g., depression, mania, and anxiety, encountered in clinical hepatic encephalopathy (HE). We therefore investigated the activity of the degradative enzyme monoamine oxidase (MAO) and its binding parameters using [ 3 H]Ro 41‐1049 (defining MAO‐A) and [ 3 H]Ro 19‐6327 (Lazabemide; defining MAO‐B) in autopsied brain tissue from male cirrhotic patients with HE. The MAO‐B parameters in HE patient tissue were not significantly different from those determined for control tissue. In contrast, increases in MAO‐A activities in HE patient frontocortical (by ∼50%) and cerebellar (by ∼145%) tissues were observed, confirming our previous findings using comparable tissues. Increases in the abundance of the active MAO‐A protein were of the same order of magnitude, e.g., in frontal cortex by ∼85% and in cerebellum by ∼225%. Reverse transcriptase‐polymerase chain reaction indicated an increase in the level of gene expression (by ∼155%) and thus offers some of the first evidence of a transcriptional event potentially mediating MAO‐A function in human brain tissue. The levels of biogenic amine acid metabolites were increased as expected. As HE patients are most often treated for their hepatic symptoms rather than their neuropsychiatric manifestations, they represent an important “untreated” psychiatric population. The present findings are therefore not only important for our understanding of the pathophysiology of HE but also extremely relevant to our understanding of the pharmacotherapy of other neuropsychiatric disorders in which biogenic amine and MAO‐A dysfunction is indicated.