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Publication : Forebrain-specific expression of monoamine oxidase A reduces neurotransmitter levels, restores the brain structure, and rescues aggressive behavior in monoamine oxidase A-deficient mice.

First Author  Chen K Year  2007
Journal  J Biol Chem Volume  282
Issue  1 Pages  115-23
PubMed ID  17090537 Mgi Jnum  J:118132
Mgi Id  MGI:3698663 Doi  10.1074/jbc.M609830200
Citation  Chen K, et al. (2007) Forebrain-specific expression of monoamine oxidase A reduces neurotransmitter levels, restores the brain structure, and rescues aggressive behavior in monoamine oxidase A-deficient mice. J Biol Chem 282(1):115-23
abstractText  Previous studies have established that abrogation of monoamine oxidase (MAO) A expression leads to a neurochemical, morphological, and behavioral specific phenotype with increased levels of serotonin (5-HT), norepinephrine, and dopamine, loss of barrel field structure in mouse somatosensory cortex, and an association with increased aggression in adults. Forebrain-specific MAO A transgenic mice were generated from MAO A knock-out (KO) mice by using the promoter of calcium-dependent kinase IIalpha (CaMKIIalpha). The presence of human MAO A transgene and its expression were verified by PCR of genomic DNA and reverse transcription-PCR of mRNA and Western blot, respectively. Significant MAO A catalytic activity, autoradiographic labeling of 5-HT, and immunocytochemistry of MAO A were found in the frontal cortex, striatum, and hippocampus but not in the cerebellum of the forebrain transgenic mice. Also, compared with MAO A KO mice, lower levels of 5-HT, norepinephrine, and DA and higher levels of MAO A metabolite 5-hydroxyindoleacetic acid were found in the forebrain regions but not in the cerebellum of the transgenic mice. These results suggest that MAO A is specifically expressed in the forebrain regions of transgenic mice. This forebrain-specific differential expression resulted in abrogation of the aggressive phenotype. Furthermore, the disorganization of the somatosensory cortex barrel field structure associated with MAO A KO mice was restored and became morphologically similar to wild type. Thus, the lack of MAO A in the forebrain of MAO A KO mice may underlie their phenotypes.
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