Mikhail Pletnikov MD, PhD

Professor of Psychiatry, Neuroscience, and Molecular and Comparative Pathobiology

mpletnik@jhmi.edu
Telephone Number: 410-502-3760
Fax Number: 410-614-0013

Johns Hopkins University
School of Medicine
600 North Wolfe Street, CMSC 8-117
Baltimore, MD 21287
Room: CMSC 8-117
Children Medical and Surgical Center
Lab Page
Areas of Research
Systems, Cognitive + Computational Neuroscience
Neural Circuits, Ensembles + Connectomes
Neurobiology of Disease

Graduate Program Affiliations

Neuroscience Training Program

Cellular and Molecular Medicine

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    Our studies have demonstrated that inducible expression of mutant DISC1 was associated with mild but significant enlargement of the lateral ventricles in transgenic mice. Three-dimensional reconstruction of the brains and ventricles (green: lateral ventricles; purple: third and fourth ventricles) from the average MRI images of the control (control) and mutant (mutant) mice. Note that the ventricle enlargement occurs in the lateral ventricles in mutant mice. DISC1 is a strong candidate gene for schizophrenia and related disorders. Our transgenic mouse model expresses mutant human DISC1 that is a predicted protein product of the chromosomal translocation present in a large Scottish pedigree described previously.

Gene-environment interactions in neurodevelopmental disorders

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.


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