TWO TYPES OF MONOAMINE OXIDASE

Summary

Principal Investigator: Jean Shih
Abstract: DESCRIPTION: The objectives of this project are to understand the[unreadable] regulation and the in-vivo function of monoamine oxidase (MAO) A and B,[unreadable] which are isoenzymes important for the degradation of monoamine[unreadable] neurotransmitters and biogenic amines. Abnormal levels of MAO activity have[unreadable] been associated with a number of mental disorders. A better understanding[unreadable] of these isoenzymes will allow for the development of more effective[unreadable] treatments for mental disorders. The specific aims are outlined below:[unreadable] [unreadable] To study the function of both MAO A and B in neurotransmitter metabolism and[unreadable] behavior using double knock-out (KO) mice MAO A and B (A/B) double KO mice[unreadable] will be generated by inactivating the MAO A gene of MAO KO mice via[unreadable] homologous recombination. PCR, Southern blot analysis, MAO catalytic[unreadable] activity and Western blot analysis will be used to ensure that both MAO A[unreadable] and B are deficient in these mice. Brain levels (whole brain and regions)[unreadable] of serotonin, norepinephrine and dopamine (MAO A substrates) and their[unreadable] metabolites will be determined in MAO A/B double KO and wild type mice by[unreadable] high pressure liquid chromatography (HPLC). Brain levels of the[unreadable] neuromodulator B-phenylethylamine (MAO B substrate) will be determined by[unreadable] Gas Chromatography/Mass Spectrometry (GC-MS). These levels will be[unreadable] correlated with MAO A and B catalytic activity. Aggressive behavior will be[unreadable] analyzed in male MAO A/B double KO mice and correlated with brain[unreadable] neurotransmitter levels.[unreadable] [unreadable] II. To investigate the role of factors F, M and Sp1 in the regulation of[unreadable] MAO B gene expression. The essential DNA bases required for factors F and M[unreadable] binding will be determined by site-directed mutagenesis and the role of each[unreadable] factor in MAO B gene expression will be identified by gel retardation and[unreadable] promoter activity assays. Using UV crosslinking experiments we will[unreadable] determine if the factors comprise of a single or multiple polypeptides.[unreadable] Full-length cDNAs encoding factors F and M will be cloned and their[unreadable] functional validity will be determined by gel retardation assays with[unreadable] expressed proteins. The cDNA encoding factor F, M and Sp1 will be[unreadable] transfected and the effect of expressed factors on MAO B expression in vivo[unreadable] will be studied by determination of promoter activity, MAO B mRNA levels,[unreadable] protein levels and catalytic activity.[unreadable] [unreadable] These studies are important for both basic neuropharmacology and clinical[unreadable] research.
Funding Period: 1985-09-01 - 2008-12-28
more information: NIH RePORT

Top Publications

  1. pmc Altered expression of tyrosine hydroxylase in the locus coeruleus noradrenergic system in citalopram neonatally exposed rats and monoamine oxidase a knock out mice
    Junlin Zhang
    Department of Anatomy, University of Mississippi Medical Center, Jackson, USA
    Anat Rec (Hoboken) 294:1685-97. 2011
  2. pmc Down-regulated GABAergic expression in the olfactory bulb layers of the mouse deficient in monoamine oxidase B and administered with amphetamine
    Hsiang Shu Yin
    Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, 100, Taiwan, ROC
    Cell Mol Neurobiol 30:511-9. 2010
  3. pmc A novel role for glyceraldehyde-3-phosphate dehydrogenase and monoamine oxidase B cascade in ethanol-induced cellular damage
    Xiao Ming Ou
    Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, Mississippi 39216, USA
    Biol Psychiatry 67:855-63. 2010
  4. pmc Monoamine oxidases regulate telencephalic neural progenitors in late embryonic and early postnatal development
    Aiwu Cheng
    Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, Maryland 21224, USA
    J Neurosci 30:10752-62. 2010
  5. pmc Maladaptive defensive behaviours in monoamine oxidase A-deficient mice
    Sean C Godar
    Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA 90089, USA
    Int J Neuropsychopharmacol 14:1195-207. 2011
  6. pmc Transcriptional regulation and multiple functions of MAO genes
    Jean C Shih
    Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, 1985 Zonal Avenue, Room 518, Los Angeles, CA 90089, USA
    J Neural Transm 118:979-86. 2011
  7. pmc Monoamine oxidase A regulates neural differentiation of murine embryonic stem cells
    Zhi Qiang Wang
    Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA 90089 9121, USA
    J Neural Transm 118:997-1001. 2011
  8. pmc Social deficits and perseverative behaviors, but not overt aggression, in MAO-A hypomorphic mice
    Marco Bortolato
    Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA 90089, USA
    Neuropsychopharmacology 36:2674-88. 2011
  9. pmc Monoamine oxidase A-mediated enhanced catabolism of norepinephrine contributes to adverse remodeling and pump failure in hearts with pressure overload
    Nina Kaludercic
    Division of Cardiology, Johns Hopkins Medical Institutions, Baltimore, MD 21205, USA
    Circ Res 106:193-202. 2010
  10. pmc Behavioral disinhibition and reduced anxiety-like behaviors in monoamine oxidase B-deficient mice
    Marco Bortolato
    Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA 90089, USA
    Neuropsychopharmacology 34:2746-57. 2009

Scientific Experts

  • Jean Shih
  • Xiao Ming Ou
  • Hsiang Shu Yin
  • Kevin Chen
  • Marco Bortolato
  • Sean C Godar
  • Anna L Scott
  • Zhi Qiang Wang
  • Junlin Zhang
  • Nina Kaludercic
  • Aiwu Cheng
  • Igor Rebrin
  • Weihua Wu
  • Gao Chen
  • Tso Jen Wang
  • Isabelle Seif
  • Zhiping Zhang
  • Soh Agatsuma
  • Qi Long Ying
  • Ryan D Darling
  • Rick C S Lin
  • Mollee R Farrell
  • Ping Li
  • Cara L Wellman
  • Roberto Frau
  • Mona Dousti
  • Kimberly L Simpson
  • Ian A Paul
  • Kathleen L Gabrielson
  • David A Kass
  • Xin Ouyang
  • Eiki Takimoto
  • Nazareno Paolocci
  • Jean Lud Cadet
  • Justin D Lathia
  • Randy D Blakely
  • Ning Feng
  • Karel Pacak
  • Mohamed Mughal
  • Mark P Mattson
  • Edwin W Lai
  • Bruce Ladenheim
  • Takahiro Nagayama
  • Fabio Di Lisa
  • Djahida Bedja
  • Shieva Davarian
  • Timothy K Gallaher
  • Wei Wen Lin
  • Yi Syuan Wu
  • Yu Shan Wang
  • Pei Lin Wu
  • Ru Band Lu
  • Hsin Yi Lo
  • Huei Chen Ko
  • Olivier Cases
  • San Yuan Huang
  • MoonSook Lee
  • Noboru Hiroi
  • Christina T Teng
  • Hongwen Zhu
  • Si Ho Choi

Detail Information

Publications21

  1. pmc Altered expression of tyrosine hydroxylase in the locus coeruleus noradrenergic system in citalopram neonatally exposed rats and monoamine oxidase a knock out mice
    Junlin Zhang
    Department of Anatomy, University of Mississippi Medical Center, Jackson, USA
    Anat Rec (Hoboken) 294:1685-97. 2011
    ..Our findings suggest that both genetic and environmental factors during early development may play a critical role in the regulation and proper function of NE TH expression in the neocortex...
  2. pmc Down-regulated GABAergic expression in the olfactory bulb layers of the mouse deficient in monoamine oxidase B and administered with amphetamine
    Hsiang Shu Yin
    Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, 100, Taiwan, ROC
    Cell Mol Neurobiol 30:511-9. 2010
    ..The data indicate that the activity of MAOB could modulate the regular and amphetamine-perturbed expression of GAD(67) and pCREB. Thus, interactions are suggested among the MAOB activity, GABA content of OlfB, and olfaction...
  3. pmc A novel role for glyceraldehyde-3-phosphate dehydrogenase and monoamine oxidase B cascade in ethanol-induced cellular damage
    Xiao Ming Ou
    Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, Mississippi 39216, USA
    Biol Psychiatry 67:855-63. 2010
    ..Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and monoamine oxidase B (MAO B) reportedly play a role in cellular dysfunction under stressful conditions and might contribute to EtOH-induced cell damage...
  4. pmc Monoamine oxidases regulate telencephalic neural progenitors in late embryonic and early postnatal development
    Aiwu Cheng
    Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, Maryland 21224, USA
    J Neurosci 30:10752-62. 2010
    ..Our findings reveal novel roles for MAOs and serotonin in the regulation of IPC proliferation in the developing brain...
  5. pmc Maladaptive defensive behaviours in monoamine oxidase A-deficient mice
    Sean C Godar
    Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA 90089, USA
    Int J Neuropsychopharmacol 14:1195-207. 2011
    ..Collectively, these results suggest that MAOA deficiency leads to a general inability to appropriately assess contextual risk and attune defensive and emotional responses to environmental cues...
  6. pmc Transcriptional regulation and multiple functions of MAO genes
    Jean C Shih
    Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, 1985 Zonal Avenue, Room 518, Los Angeles, CA 90089, USA
    J Neural Transm 118:979-86. 2011
    ..This review discusses the recent progress in the transcriptional regulation and multiple functions of MAO A and MAO B genes...
  7. pmc Monoamine oxidase A regulates neural differentiation of murine embryonic stem cells
    Zhi Qiang Wang
    Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA 90089 9121, USA
    J Neural Transm 118:997-1001. 2011
    ..Our results show that the differentiation to neural cells in MAO A(neo) ES cells was reduced compared to WT, suggesting MAO A played a regulatory role in stem cells neural differentiation...
  8. pmc Social deficits and perseverative behaviors, but not overt aggression, in MAO-A hypomorphic mice
    Marco Bortolato
    Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA 90089, USA
    Neuropsychopharmacology 36:2674-88. 2011
    ..Taken together, our findings indicate that MAO A hypomorphism results in behavioral and morphological alterations distinct from those featured by MAO-A KO mice...
  9. pmc Monoamine oxidase A-mediated enhanced catabolism of norepinephrine contributes to adverse remodeling and pump failure in hearts with pressure overload
    Nina Kaludercic
    Division of Cardiology, Johns Hopkins Medical Institutions, Baltimore, MD 21205, USA
    Circ Res 106:193-202. 2010
    ..Because excess reactive oxygen species and catecholamines are major contributors to the pathophysiology of congestive heart failure, MAOs could play an important role in this process...
  10. pmc Behavioral disinhibition and reduced anxiety-like behaviors in monoamine oxidase B-deficient mice
    Marco Bortolato
    Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA 90089, USA
    Neuropsychopharmacology 34:2746-57. 2009
    ..Taken together, these results suggest that MAO B deficiency may lead to behavioral disinhibition and decreased anxiety-like responses partially through regional increases of PEA levels...
  11. pmc Glyceraldehyde-3-phosphate dehydrogenase-monoamine oxidase B-mediated cell death-induced by ethanol is prevented by rasagiline and 1-R-aminoindan
    Xiao Ming Ou
    Division of Neurobiology and Behavioral Research, Department of Psychiatry and Human Behavior G 109, University of Mississippi Medical Center, 2500 N State Street, Jackson, MS 39216, USA
    Neurotox Res 16:148-59. 2009
    ....
  12. pmc Monoamine oxidase inactivation: from pathophysiology to therapeutics
    Marco Bortolato
    Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA 90089, USA
    Adv Drug Deliv Rev 60:1527-33. 2008
    ..This possibility further highlights MAO inactivation as a rich source of novel avenues in the treatment of mental disorders...
  13. ncbi Estrogen-related receptors-stimulated monoamine oxidase B promoter activity is down-regulated by estrogen receptors
    Zhiping Zhang
    Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    Mol Endocrinol 20:1547-61. 2006
    ..These studies provide new insight into the relationship between ERalpha, ERbeta, ERRalpha, and ERRgamma in modulation of MAO-B gene activity...
  14. ncbi Glucocorticoid and androgen activation of monoamine oxidase A is regulated differently by R1 and Sp1
    Xiao Ming Ou
    Department of Molecular Pharmacology and Toxicology, School of Pharmacy, University of Southern California 90033, USA
    J Biol Chem 281:21512-25. 2006
    ..Androgen receptor indirectly interacts with the Sp1, but not R1 transcription factor, on Sp1-binding sites. This study provides new insights on the differential regulation of MAO A by glucocorticoid and androgen...
  15. pmc Monoamine oxidase A and repressor R1 are involved in apoptotic signaling pathway
    Xiao Ming Ou
    Department of Molecular Pharmacology and Toxicology, School of Pharmacy, University of Southern California, Los Angeles, CA 90033, USA
    Proc Natl Acad Sci U S A 103:10923-8. 2006
    ..In summary, this study demonstrates the functions of MAO A and its repressor R1 in apoptotic signaling pathways...
  16. ncbi Monoamine oxidase A knockout mice exhibit impaired nicotine preference but normal responses to novel stimuli
    Soh Agatsuma
    Laboratory of Molecular Psychobiology, Department of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    Hum Mol Genet 15:2721-31. 2006
    ..Constitutive MAOA activity levels are likely to contribute to the vulnerability or resiliency to nicotine addiction by altering the rewarding effects of nicotine...
  17. ncbi Possible interaction between MAOA and DRD2 genes associated with antisocial alcoholism among Han Chinese men in Taiwan
    Tso Jen Wang
    Graduate Institute of Medical Sciences, National Defense Medical Center, Taiwan, ROC Tsaotun Psychiatric Center, Department of Health, Nantou, Taiwan, ROC
    Prog Neuropsychopharmacol Biol Psychiatry 31:108-14. 2007
    ..We concluded that the possible interactions between MAOA-uVNTR polymorphism and DRD2 TaqI A polymorphism might be related to Antisocial ALC among Han Chinese men in Taiwan...
  18. pmc 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
    Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, California 90089, USA
    J Biol Chem 282:115-23. 2007
    ..Thus, the lack of MAO A in the forebrain of MAO A KO mice may underlie their phenotypes...
  19. ncbi Monoamine oxidases: from tissue homogenates to transgenic mice
    Jean Chen Shih
    Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, 1985 Zonal Avenue, Los Angeles, CA 90089, USA
    Neurochem Res 32:1757-61. 2007
    ....
  20. pmc Novel monoamine oxidase A knock out mice with human-like spontaneous mutation
    Anna L Scott
    Department of Pharmacology and Pharmaceutical Sciences, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA
    Neuroreport 19:739-43. 2008
    ..These findings consolidate evidence linking MAO A to aggression and highlight subtle yet distinctive phenotypical characteristics...
  21. pmc R1, a novel repressor of the human monoamine oxidase A
    Kevin Chen
    Department of Molecular Pharmacology and Toxicology, School of Pharmacy, University of California, Los Angeles, California 90033, USA
    J Biol Chem 280:11552-9. 2005
    ..Northern blot analysis revealed the presence of endogenous R1 mRNA in human brain and peripheral tissues. Taken together, this study shows that R1 is a novel repressor that inhibits monoamine oxidase A gene expression...