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

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. 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. 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. 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. 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. 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. 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. Schizophrenia is a Developmental Disorder
(Jaaro-Peled et al., TINS, 2009)

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. Acknowledgements
Pletnikov lab
Geetha Kannan
Chunxia Yang
Bagrat Abazyan
Alexey Shevelkin
Meng Xia
Sofya Abazyan
Michelle Potter
Fabrice Casseus
Joshua Crawford
The Stanley Division at Hopkins
Robert Yolken
Lori Brando
J-C Xiao
Emily Severance
Sarven Sabunciyan
JHU Schizophrenia Conte Center
Akira Sawa
Supported by the Stanley Medical Research Institute, NIMH