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School of Medicine
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Faculty Director: Mikhail V. Pletnikov, M.D., Ph.D
Our laboratory is interested in the neurobiology of neurodevelopmental diseases such as schizophrenia and autism. The major focus of the laboratory is to evaluate how adverse environmental factors and vulnerable genes interact to affect brain and behavior development. We address these experimental questions by using methods of cell and molecular biology, neuroimmunology, neurochemistry, psychopharmacology and developmental psychobiology.
The current projects in our laboratory are:
Genetic risk factors in neuron-astrocyte interaction during neurodevelopment
We have been developing and characterizing cell and animal models of inducible expression of a mutant human gene, disrupted-in-schizophrenia-1, which is disrupted due to a chromosomal translocation in a large Scottish pedigree which segregates with major mental illnesses. Recently, we have initiated a new program to elucidate the roles for schizophrenia genetic risk factors in neuron-astrocyte interaction during neurodevelopment. In collaboration with the laboratory of Dr. Solomon H. Snyder (Neuroscience), we evaluate the mechanisms whereby DISC1 regulates the enzymatic activity of serine racemase in astrocytes to produce D-serine, a critical co-agonist of NMDA receptors. In collaboration with the laboratory of Dr. Dwight Bergles (Neuroscience), we study the roles for DISC1 in astrocytes during neurodevelopment.
Gene-environment interplay in the pathogenesis of psychiatric conditions
Utilizing our transgenic DISC1 cell and mouse models, we study the pathways whereby adverse environmental factors such viral infection, stress, or malnutrition interact with the genetic mutations at molecular, cellular, and system levels. The ultimate goal of this research program is to identify molecular pathways that mediate specific gene-environment interactions that could serve potential targets for novel therapeutic interventions.
The neuroimmune interactions in abnormal neurodevelopment
Dysregulation in neuroimmune mechanisms is believed to be crucial to the interplay between genes and environment in mental illnesses. We use several approaches to elucidate the mechanisms of contribution of neuroinflammation to abnormal brain functioning. In collaboration with Dr Harvey Singer (Neurology), we study putative autoimmune mechanisms potentially responsible for abnormal brain development that could result in autism-like conditions. In collaboration with Dr. Carlos Pardo-Vallamizar (Neurology), we analyze the role of neuroimmune mechanisms in mediating the neurobehavioral effects of prenatal immune activation and secreted cytokines in associated with autism spectrum disorders.
Undergraduate, graduate students, fellows, and faculty members are welcome to join the laboratory to take part in basic research training and/or collaborations.
Graduate Students (CMM)
Kannan G, Pletnikov MV. Toxoplasma Gondii and Cognitive Deficits in Schizophrenia: An Animal Model Perspective. Schizophr Bull. 2012 Sep 1.
Ma TM, Abazyan S, Abazyan B, Nomura J, Yang C, Seshadri S, Sawa A, Snyder SH, Pletnikov MV. Pathogenic disruption of DISC1-serine racemase binding elicits schizophrenia-like behavior via D-serine depletion. Mol Psychiatry. 2012 Jul 17.
Abazyan B, Nomura J, Kannan G, Ishizuka K, Tamashiro KL, Nucifora F, PogorelovV, Ladenheim B, Yang C, Krasnova IN, Cadet JL, Pardo C, Mori S, Kamiya A, Vogel MW, Sawa A, Ross CA, Pletnikov MV. Prenatal interaction of mutant DISC1 and immune activation produces adult psychopathology. Biol Psychiatry. 2010 Dec15;68(12):1172-81. Erratum in: Biol Psychiatry. 2011 Feb 15;69(4):390.
Ayhan Y, Abazyan B, Nomura J, Kim R, Ladenheim B, Krasnova IN, Sawa A, Margolis RL, Cadet JL, Mori S, Vogel MW, Ross CA, Pletnikov MV. Differential effects of prenatal and postnatal expressions of mutant human DISC1 on neurobehavioral phenotypes in transgenic mice: evidence for neurodevelopmental origin of major psychiatric disorders. Mol Psychiatry. 2011 Mar;16(3):293-306.
Ayhan Y, Sawa A, Ross CA, Pletnikov MV. Animal models of gene-environment interactions in schizophrenia. Behav Brain Res. 2009 Dec 7;204(2):274-81.
Ross CA, Margolis RL, Reading SA, Pletnikov M, Coyle JT. Neurobiology of schizophrenia. Neuron. 2006 Oct 5;52(1):139-53.