New theories of schizophrenia present it as a disease of myelination. This project proposes to examine and quantify changes in oligodendrocytes and myelination in the cingulum bundle of schizophrenics. A deeper understanding of the pathophysiology of schizophrenia may lead to innovative treatments for this chronic disease. A second-order stereologic approach will be used to quantify changes in the spatial distribution of oligodendrocytes in the cingulum bundle of human schizophrenics, using postmortem materials. A mouse model genetically engineered to be missing MAG, a myelin-related protein, will be studied to quantify changes in prefrontal cortical pyramidal cells that may be affected by dysmyelination. Cell morphology, dendritic arborization, and myelination will be compared across mutant and wildtype mice. In addition, diffusion tensor imaging will be used to compare anisotropy between living schizophrenic patients and controls. The anisotropy data will be correlated with changes in metabolism observed by PET imaging and will also be compared across stages of the disease. The same data will allow tracing of the cingulum bundle in schizophrenics and controls to look for differences in fiber targeting. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
8F30MH082286-02
Application #
7216322
Study Section
Special Emphasis Panel (ZRG1-F01 (20))
Program Officer
Rubio, Mercedes
Project Start
2006-01-03
Project End
2009-05-31
Budget Start
2007-04-01
Budget End
2008-03-31
Support Year
2
Fiscal Year
2007
Total Cost
$31,268
Indirect Cost
Name
Mount Sinai School of Medicine
Department
Neurosciences
Type
Schools of Medicine
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029
Segal, Devorah; Haznedar, M Mehmet; Hazlett, Erin A et al. (2010) Diffusion tensor anisotropy in the cingulate gyrus in schizophrenia. Neuroimage 50:357-65
Segal, Devorah; Schmitz, Christoph; Hof, Patrick R (2009) Spatial distribution and density of oligodendrocytes in the cingulum bundle are unaltered in schizophrenia. Acta Neuropathol 117:385-94