A series of quantitative microscopic studies which have been completed in this laboratory has demonstrated that in schizophrenic brain there is no evidence for a process of neuronal degeneration in the prefrontal, anterior cingulate or primary motor cortex. The evidence does suggest, however, that novel cytoarchitectural variations, particularly in anterior cingulate cortex, may occur in relation to this disorder. In the region of layer II of the cingulate cortex, there may be a unique structural variation in which there are smaller domains or aggregates of neurons with a diameter of approximately 300 microm, as well as greater numbers of long, vertical axons which may be associative in nature. This proposal describes a series of quantitative morphometric and immunocytochemical studies of the cerebral cortex which aim to replicate and extend these earlier studies in a new cohort of schizophrenics to test the reliability of these findings. In addition, patients with psychosis in the setting of primary effective disorder will also be studied, so that the effects of long-term psychosis and/or neuroleptic exposure can be evaluated. The studies to be done include: a) determinations of cell counts and neuronal cell size; b) computer-assisted analyses of the spatial arrangement of neurons along distances ranging up to 400 microm; c) three-dimensional reconstructions of tracings of neurons, and possibly axons, in order to determine whether macrocolumnar differences in anterior cingulate cortex may occur; d) quantitation of immunocytochemical reaction product for markers of axons, dendrites and functional synapses by either microdensitometry or manual counting.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH042261-02
Application #
3381437
Study Section
(BPNB)
Project Start
1987-09-01
Project End
1990-07-31
Budget Start
1988-08-01
Budget End
1989-07-31
Support Year
2
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Mc Lean Hospital (Belmont, MA)
Department
Type
DUNS #
City
Belmont
State
MA
Country
United States
Zip Code
02478
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Subburaju, Sivan; Benes, Francine M (2012) Induction of the GABA cell phenotype: an in vitro model for studying neurodevelopmental disorders. PLoS One 7:e33352
Sheng, Guoqing; Demers, Matthew; Subburaju, Sivan et al. (2012) Differences in the circuitry-based association of copy numbers and gene expression between the hippocampi of patients with schizophrenia and the hippocampi of patients with bipolar disorder. Arch Gen Psychiatry 69:550-61
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Benes, Francine M; Lim, Benjamin; Subburaju, Sivan (2009) Site-specific regulation of cell cycle and DNA repair in post-mitotic GABA cells in schizophrenic versus bipolars. Proc Natl Acad Sci U S A 106:11731-6
Lisman, John E; Coyle, Joseph T; Green, Robert W et al. (2008) Circuit-based framework for understanding neurotransmitter and risk gene interactions in schizophrenia. Trends Neurosci 31:234-42
Woo, Tsung-Ung W; Shrestha, Kevin; Lamb, Dorian et al. (2008) N-methyl-D-aspartate receptor and calbindin-containing neurons in the anterior cingulate cortex in schizophrenia and bipolar disorder. Biol Psychiatry 64:803-9
Buttner, Ned; Bhattacharyya, Sujoy; Walsh, John et al. (2007) DNA fragmentation is increased in non-GABAergic neurons in bipolar disorder but not in schizophrenia. Schizophr Res 93:33-41
Benes, Francine M; Lim, Benjamin; Matzilevich, David et al. (2007) Regulation of the GABA cell phenotype in hippocampus of schizophrenics and bipolars. Proc Natl Acad Sci U S A 104:10164-9

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