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Expression of neuronal nitric oxide synthase in the hippocampal formation in affective disorders
Oliveira, R. M. W; Guimarães, F. S; Deakin, J. F. W.
  • Oliveira, R. M. W; Universidade Estadual de Maringá. Departamento de Farmácia e Farmacologia. Maringá. BR
  • Guimarães, F. S; Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Ribeirão Preto. BR
  • Deakin, J. F. W; The University of Manchester. Neuroscience and Psychiatry Unit. Manchester. GB
Braz. j. med. biol. res ; 41(4): 333-341, Apr. 2008. ilus, tab
Article in English | LILACS | ID: lil-479683
ABSTRACT
Hippocampal output is increased in affective disorders and is mediated by increased glutamatergic input via N-methyl-D-aspartate (NMDA) receptor and moderated by antidepressant treatment. Activation of NMDA receptors by glutamate evokes the release of nitric oxide (NO) by the activation of neuronal nitric oxide synthase (nNOS). The human hippocampus contains a high density of NMDA receptors and nNOS-expressing neurons suggesting the existence of an NMDA-NO transduction pathway which can be involved in the pathogenesis of affective disorders. We tested the hypothesis that nNOS expression is increased in the human hippocampus from affectively ill patients. Immunocytochemistry was used to demonstrate nNOS-expressing neurons in sections obtained from the Stanley Consortium postmortem brain collection from patients with major depression (MD, N = 15), bipolar disorder (BD, N = 15), and schizophrenia (N = 15) and from controls (N = 15). nNOS-immunoreactive (nNOS-IR) and Nissl-stained neurons were counted in entorhinal cortex, hippocampal CA1, CA2, CA3, and CA4 subfields, and subiculum. The numbers of Nissl-stained neurons were very similar in different diagnostic groups and correlated significantly with the number of nNOS-IR neurons. Both the MD and the BD groups had greater number of nNOS-IR neurons/400 µm² in CA1 (mean ± SEM MD = 9.2 ± 0.6 and BD = 8.4 ± 0.6) and subiculum (BD = 6.7 ± 0.4) when compared to control group (6.6 ± 0.5) and this was significantly more marked in samples from the right hemisphere. These changes were specific to affective disorders since no changes were seen in the schizophrenic group (6.7 ± 0.8). The results support the current view of the NMDA-NO pathway as a target for the pathophysiology of affective disorders and antidepressant drug development.
Subject(s)

Full text: Available Index: LILACS (Americas) Main subject: Schizophrenia / Bipolar Disorder / Depressive Disorder, Major / Nitric Oxide Synthase Type I / Hippocampus Type of study: Observational study Limits: Adult / Female / Humans / Male Language: English Journal: Braz. j. med. biol. res Journal subject: Biology / Medicine Year: 2008 Type: Article Affiliation country: Brazil / United kingdom Institution/Affiliation country: The University of Manchester/GB / Universidade Estadual de Maringá/BR / Universidade de São Paulo/BR

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Full text: Available Index: LILACS (Americas) Main subject: Schizophrenia / Bipolar Disorder / Depressive Disorder, Major / Nitric Oxide Synthase Type I / Hippocampus Type of study: Observational study Limits: Adult / Female / Humans / Male Language: English Journal: Braz. j. med. biol. res Journal subject: Biology / Medicine Year: 2008 Type: Article Affiliation country: Brazil / United kingdom Institution/Affiliation country: The University of Manchester/GB / Universidade Estadual de Maringá/BR / Universidade de São Paulo/BR