Behavioral Neurobiology and Neuroimmunology Laboratory

Faculty Director: Mikhail V. Pletnikov, M.D., Ph.D

Link to PubMed publications for Pletnikov, M

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:

Cell and mouse models of inducible expression of disrupted-in-schizophrenia-1 (DISC1)

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. The in vitro part of the project is focused on evaluation of the molecular and cellular effects mutant human DISC1 using stable clones of neuron-like PC12 cells?and primary neurons with inducible expression of the mutant and wild-type DISC1 proteins. The in vivo part of the research project aims at characterizing the neurobehavioral effects of mutant hDISC1 in transgenic mice across the entire life span. By regulating when during development and where in the brain mutant hDISC1 is expressed, we seek to identify the critical periods and brain regions important for the effects of mutant hDISC1 to take place.

Gene-environment interplay in the pathogenesis of psychiatric conditions

Utilizing our transgenic DISC1 cell and mouse models, we are studying 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. Using a neonatal Borna disease virus infection model, we are trying to understand how interactions between neurons, astrocytes and microglia shape neuro-inflammatory response in the brain, leading to neuronal dysfunction, damage or death with associated behavioral deficits. In collaboration with Dr Harvey Singer (Neurology), we have been studying putative autoimmune mechanisms potentially responsible for abnormal brain development that could result in autism-like conditions. In collaboration with Drs. Andrew Zimmerman (Kennedy Krieger Institute) and Carlos Pardo-Vallamizar (Neurology), we have been studying a role of neuroimmune mechanisms in mediating the neurobehavioral effects of terbutaline that has been associated with some case of autism spectrum disorders. In collaboration with Dr Ellen K. Silbergeld (Environmental Health Sciences, Johns Hopkins?Bloomberg School of Public Health), we have been studying interactions between various adverse environmental factors in the pathogenesis of abnormal brain maturation.

Undergraduate, graduate students, fellows, and faculty members are welcome to join the laboratory to take part in basic research training and/or collaborations.

LAB MEMBERS

SELECTED REFERENCES

Pletnikov MV, Rubin SA, Vasudevan K, Moran TH, Carbone KM. Developmental brain injury associated with abnormal play behavior in neonatally Borna disease virus-infected Lewis rats: a model of autism. Behav Brain Res. 1999 Apr;100(1-2):43-50.

Pletnikov MV, Moran TH, Carbone KM.?Borna disease virus infection of the neonatal rat: developmental brain injury model of autism spectrum disorders. Front Biosci. 2002 Mar 1;7:d593-607.

Sawa A, Pletnikov MV, Kamiya A. Neuron-glia interactions clarify genetic-environmental links in mental illness. Trends Neurosci. 2004 Jun;27(6):294-7.

Ovanesov MV, Sauder C, Rubin SA, Richt J, Nath A, Carbone KM, Pletnikov MV. Activation of microglia by borna disease virus infection: in vitro study. J Virol. 2006 Dec;80(24):12141-8.

Ross CA, Margolis RL, Reading SA, Pletnikov M, Coyle JT. Neurobiology of schizophrenia. Neuron. 2006 Oct 5;52(1):139-53.

Lancaster K, Dietz DM, Moran TH, Pletnikov MV. Abnormal social behaviors in young and adult rats neonatally infected with Borna disease virus. Behav Brain Res. 2007, 176(1):141-8.

Pletnikov MV, Xu Y, Ovanesov MV, Kamiya A, Sawa A, Ross CA. PC12 cell model of inducible expression of mutant DISC1: New evidence for a dominant-negative mechanism of abnormal neuronal differentiation. Neurosci Res. 2007.

See also the Department's Schizophrenia Program