HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 282, Issue 1, 115-123, January 5, 2007

This Article Full Text Full Text (PDF) All Versions of this Article: 282/1/115    most recent M609830200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Chen, K. Articles by Shih, J. C. Search for Related Content PubMed PubMed Citation Articles by Chen, K. Articles by Shih, J. C. Social Bookmarking                      What's this?

Forebrain-specific Expression of Monoamine Oxidase A Reduces Neurotransmitter Levels, Restores the Brain Structure, and Rescues Aggressive Behavior in Monoamine Oxidase A-deficient Mice^*

Kevin Chen, Olivier Cases¹, Igor Rebrin, Weihua Wu, Timothy K. Gallaher, Isabelle Seif^¶, and Jean Chen Shih^||2

From the Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, California 90089, the ^||Department of Cell and Neurobiology, School of Medicine, University of Southern California, Los Angeles, California 90089, INSERM U676, Bâtiment Ecran, Hôpital Robert Debré, 48 Boulevard Sérurier, 75019 Paris, France, and ^¶CNRS, Unité Mixte de Recherche 146, Institut Curie, 91405 Orsay, France

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 II (CaMKII). 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.

Received for publication, October 18, 2006 , and in revised form, November 6, 2006.

^* This work was supported in part by National Institute for Mental Health Grants R37 MH39085 (MERIT Award) and RO1 MH067968 and the Boyd and Elsie Welin professorship award (to J. C. S.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Recipient of support from the CNRS.

² To whom correspondence should be addressed: Dept. of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Rm. 518, 1985 Zonal Ave., Los Angeles, CA 90089. Tel.: 323-442-1441; Fax: 323-442-3229; E-mail: jcshih{at}hsc.usc.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?