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

• Published in: Schizophrenia research Vol. 87; no. 1; pp. 6 - 14
• Main Authors: Broadbelt, Kevin, Ramprasaud, Andrew, Jones, Liesl B.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.10.2006; Elsevier Science
• Subjects: Adult; Adult and adolescent clinical studies; Aged; Biological and medical sciences; Blotting, Western; Calcium; Cell Count; Cortex; Dendrite; Dendrites - immunology; Dendrites - metabolism; Dendrites - pathology; Female; Humans; Immunocytochemistry; Immunohistochemistry - methods; Male; Medical sciences; Middle Aged; Morphology; Neurogranin - immunology; Neurogranin - metabolism; Phosphorylation; Prefrontal Cortex - immunology; Prefrontal Cortex - metabolism; Prefrontal Cortex - pathology; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychoses; Pyramidal Cells - immunology; Pyramidal Cells - metabolism; Pyramidal Cells - pathology; Schizophrenia; Schizophrenia - immunology; Schizophrenia - metabolism; Schizophrenia - pathology; Signal Transduction - physiology; Schizophrenia; Calcium; Immunocytochemistry; Morphology; Cortex; Dendrite; Human; Central nervous system; Prefrontal cortex; Inorganic element; Encephalon; Psychosis; Anatomic pathology
• ISSN: 0920-9964; 1573-2509
• DOI: 10.1016/j.schres.2006.04.028

Schizophrenia is a complex and poorly understood neuropsychiatric disorder. Much research has begun to implicate the prefrontal cortex in the disease. Using immunocytochemistry we determined if neurogranin, a protein found in dendrites, spines and cell bodies and an upstream regulator of calcium was altered in areas 9 and 32 of schizophrenic prefrontal cortex. We examined its expression in pyramidal cells in layers III and V. Tissues from 7 controls and 7 schizophrenics (from our original MAP2 study, Jones, L., Johnson, N., Byne, W., 2002. Alterations in MAP2 staining in area 9 and 32 of schizophrenic prefrontal cortex. Psych. Res. 114, 137–148) matched for age, sex and postmortem interval were examined. Using area fraction analysis we quantified the immunostaining. Additionally, we counted the number of positively stained pyramidal cells in the same 7 pairs. Neurogranin immunostaining was dramatically reduced in both layers III (72%) and V (50%) in area 9. In area 32 there was a more modest reduction in both layers III (36%) and V (40%). There was no difference in either brain region or layer in the density of positively stained pyramidal cells. These data confirm mounting evidence suggesting dendritic loss in the prefrontal cortex and suggest that the loss of protein does not appear to be due to a change in the number of cells producing the protein but rather in the amount of protein being produced. Additionally, these data suggest that the loss of neurogranin may alter the calcium–calmodulin dependent pathways due to its role as a regulator of calmodulin suggesting a link between structural and functional alterations of the pyramidal cells in the prefrontal cortex.