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J Psychiatr Res. 2008 Jul;42(8):612-21. doi: 10.1016/j.jpsychires.2007.07.006. Epub 2008 Mar 4.

Evidence of altered calmodulin immunoreactivity in areas 9 and 32 of schizophrenic prefrontal cortex.

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Lehman College, CUNY, Department of Biological Sciences, 250 Bedford Park Blvd., Bronx, NY 10468, USA.


Schizophrenia is a severe neuropsychiatric disorder. Previous studies have implicated the prefrontal cortex (PFC) [Harrison PJ. The neuropathology of schizophrenia a critical review of the data and their interpretation. Brain 1999;122:593-624; Jones LB. Recent cytoarchitectonic changes in the prefrontal cortex of schizophrenics. Frontiers of Bioscience 2001;6:E148-53]. Recent immunocytochemical studies have shown a dramatic decrease in MAP2 and neurogranin [Jones L, Johnson N, Byne W. Alterations in MAP2 staining in area 9 and 32 of schizophrenic prefrontal cortex. Psychiatry Research 2002;114:137-48; Broadbelt K, Pamprasaud A, Jones LB. Evidence of altered neurogranin immunoreactivity in areas 9 and 32 of schizophrenic prefrontal cortex. Schizophrenia Research 2006;87:6-14] a loss of either is suggestive of dendritic lesions [Li GL, Farooque M, Lewen A., Lennmyr F, Holtz A., Olsson Y. MAP2 and neurogranin as markers for dendritic lesions in cns injury an immunohistochemical study in the rat. APMIS 2002;108:98-106.]. Neurogranin is an upstream regulator of calcium and calmodulin [Prichard L, Deloulmes JC, Storm DR. Interactions between Neurogranin and Calmodulin in vivo. Journal of Biological Chemistry 1999;274:7689-94]. A direct action of this pathway is the phosphorylation of MAP2, which is required for microtubule stabilization. Because of the above findings as well as moropholigical alterations [Broadbelt K, Byne W, Jones LB. Evidence for a decrease in primary and secondary basilar dendrites on pyramidal cells in area 32 of schizophrenic prefrontal cortex. Schizophrenia Research 2002;58:75-81] we examined the expression of the active form of calmodulin in layers III and V of areas 9 and 32 in six controls and six schizophrenics matched for age, sex, and postmortem interval. Using area fraction analysis we quantified immunostaining and counted the number of immunopositive pyramidal cells and interneurons as well as immunonegative pyramidal cells. Area fraction analysis showed a significant decrease in immunostaining in area nine layers III (58%) and V (44%), area 32 layers III (51%) and V (32%). We found a significant reduction in the density of immunopositive pyramidal cells in area 9 (11%) layer III, (20%) layer V, area 32 (16%) layer III and (17%) layer V with no difference in immunopositive interneurons. These data suggest a loss of the active form of calmodulin with pyramidal cells being preferentially affected suggesting that the calcium calmodulin dependent pathway may be altered in the pyramidal cells in the PFC.

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