Kannan and Pletnikov


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presentation made by Dr. Misha Pletnikov November 13, 2012 on the Schizophrenia Research Forum (www.schizophreniaforum.org).

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  • Kannan and Pletnikov

    1. 1. Toxoplasma gondii and cognitive deficits in schizophrenia: an animal model perspective G. Kannan and M. Pletnikov Departments of Psychiatry and Behavioral Sciences, Neuroscience, Molecular and Comparative Pathobiology Johns Hopkins University School of Medicine Baltimore, Maryland
    2. 2. Animal models of mental disease• Replicating psychiatric symptoms is a daunting task• Animal model needs to address the specific question• Various approaches – Using etiologically relevant environmental and/or genetic risk factors to better understand the underlying neurobiology of psychiatric disease
    3. 3. Animal models of T. gondii infection• A microbial pathogen relevant to schizophrenia• Many infections have species-specific mechanisms and pose challenges for animal models• T. gondii infection likely involves the similar mechanisms in humans and animals
    4. 4. Cognitive deficits in schizophrenia• Least amenable to treatment• Learning and memory tests to study cognitive impairment – Translational potential vs. other tests – Similar underlying biology • Synaptic pathology• Complexity of T. gondii effects on cognition – Please, see Table in our review for diversity of effects • Type or strain of T. gondii • Sex-dependent effects • Time of infection
    5. 5. T. gondii strain-related cognitive deficit Working memory Spatial recognition 80 80% of alternations 60 * 60 Time (sec) 40 40 20 20 0 0 Control PRU ME49 Control PRU ME49 Kannan et al, 2010
    6. 6. Sex-dependent cognitive impairment Social transmission of food preference 120 100 Control% Cued food /total PRU 80 60 40 20 0 Male Female Xia, Kannan et al, 2012
    7. 7. Time-dependent disruption of pre-pulse inhibition 80 DPBS PRU Juvenile 60 40 * 20% of PPI 0 p4 p8 p12 p16 p20 80 Control Adult 60 PRU 40 20 0 p4 p8 p12 p16 p20 Pre-pulse levels Kannan et al, prelim data
    8. 8. Schizophrenia is a Developmental Disorder (Jaaro-Peled et al., TINS, 2009)
    9. 9. Targeting glutamatergic synapses• Effects of pro-inflammatory factors on glutamatergic synaptic neurotransmission• Major histocompatibility complex class I (MHCI) molecules in neuroplasticity• Decreased expression of NMDA receptors on GABA neurons as a result of GABA neurons dysfunction due to neuroinflammation• Elevated levels of KYNA to antagonize NMDA receptors• Auto-antibodies to NMDA receptors
    10. 10. AcknowledgementsPletnikov labGeetha KannanChunxia YangBagrat AbazyanAlexey ShevelkinMeng XiaSofya AbazyanMichelle PotterFabrice CasseusJoshua CrawfordThe Stanley Division at HopkinsRobert YolkenLori BrandoJ-C XiaoEmily SeveranceSarven SabunciyanJHU Schizophrenia Conte CenterAkira Sawa Supported by the Stanley Medical Research Institute, NIMH