Naoya Nishioka1, Steven E Arnold. 1. Cellular and Molecular Neuropathology Program, Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania, Philadelphia, PA 19104, USA.
Abstract
OBJECTIVE: The authors investigated the idea that some patients with schizophrenia exhibit a chronic, deteriorating course without showing frank neurodegeneration at postmortem examination. Oxidative damage is one form of cellular injury that may cause cellular dysfunction without necessarily leading to neuron death. METHODS: Authors obtained postmortem hippocampi from 13 elderly non-psychiatric comparison cases and 10 patients with "poor-outcome" schizophrenia. The groups were compared for the presence of neuronal 8-hydroxy, 2' deoxyguanosine (8-OHdG), a robust marker of oxidized DNA, and neuronal Ki-67, a marker of cell-cycle activation, as well as neurofibrillary tangles, amyloid-beta senile plaques, and astrocytosis. RESULTS: The mean proportion of neurons exhibiting 8-OHdG immunoreactivity was 10 times higher in schizophrenia than in comparison cases. Ki-67 was similarly elevated and was correlated with 8-OHdG in the schizophrenia group. There were no significant between-group differences for densities of neurofibrillary tangles, amyloid-beta plaques, or astrocytes. CONCLUSIONS: Our data provide evidence for oxidative DNA damage and coordinated cell-cycle activation in elderly "poor-outcome" schizophrenia. These findings could have important implications for cellular metabolism, gene expression, and membrane functioning in schizophrenia.
OBJECTIVE: The authors investigated the idea that some patients with schizophrenia exhibit a chronic, deteriorating course without showing frank neurodegeneration at postmortem examination. Oxidative damage is one form of cellular injury that may cause cellular dysfunction without necessarily leading to neuron death. METHODS: Authors obtained postmortem hippocampi from 13 elderly non-psychiatric comparison cases and 10 patients with "poor-outcome" schizophrenia. The groups were compared for the presence of neuronal 8-hydroxy, 2' deoxyguanosine (8-OHdG), a robust marker of oxidized DNA, and neuronal Ki-67, a marker of cell-cycle activation, as well as neurofibrillary tangles, amyloid-beta senile plaques, and astrocytosis. RESULTS: The mean proportion of neurons exhibiting 8-OHdG immunoreactivity was 10 times higher in schizophrenia than in comparison cases. Ki-67 was similarly elevated and was correlated with 8-OHdG in the schizophrenia group. There were no significant between-group differences for densities of neurofibrillary tangles, amyloid-beta plaques, or astrocytes. CONCLUSIONS: Our data provide evidence for oxidative DNA damage and coordinated cell-cycle activation in elderly "poor-outcome" schizophrenia. These findings could have important implications for cellular metabolism, gene expression, and membrane functioning in schizophrenia.
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