A reduced number of cortical neurons show increased Caldendrin protein levels in chronic schizophrenia

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• 作者：Hans-Gert Bernstein ; Jale Sahin ; Karl-Heinz Smalla ; Eckart D. Gundelfinger ; Bernhard Bogerts ; Michael R. Kreutz
• 关键词：Caldendrin ; Neuronal Ca²⁺-sensor ; Synapse ; Chronic schizophrenia ; Postsynaptic density ; SAP97 ; Left dorsolateral prefrontal cortex ; Quantitative immunoblotting
• 刊名：Schizophrenia Research
• 出版年：2007
• 期刊代码：240_09209964
• 类别：med
• 出版时间：November 2007
• 卷：96
• 期：1-3
• 页码：246-256
• 文件大小：857 K

摘要

Caldendrin is a neuronal calcium sensor protein that is tightly associated with the postsynaptic density (PSD) of excitatory synapses. It has an established role in synapto-dendritic Ca²⁺-signaling as a multifunctional regulator of intracellular Ca²⁺ levels. Previous work has shown that expression levels of protein components involved in signaling processes at excitatory synapses are significantly altered in the brains of schizophrenic patients. Furthermore, it is widely accepted that synaptic pathology associated with the glutamatergic N-methyl-d-aspartate (NMDA) receptor is a feature of the disease. Here we report that in postmortem brains of chronic schizophrenics (N: 12) as compared to age-and sex-matched controls (N: 12) the number of Caldendrin-immunoreactive neurons are significantly reduced in the left dorsolateral prefrontal cortex, a brain region prominently associated with schizophrenia. Less dramatic changes were observed in other cortical regions. However, despite the reduced number of immunoreactive neurons, absolute Caldendrin protein levels were elevated and no change in Caldendrin PSD-levels were observed as compared to the left dorsolateral prefrontal cortex in the normal human brain. Thus, synapto-dendritic Ca²⁺-signaling via Caldendrin is altered in schizophrenic patients by a redistribution of the protein into a lower number of pyramidal neurons, which express higher Caldendrin levels. Since Caldendrin is a multivalent regulator of voltage dependent Ca²⁺-channels and Ca²⁺-release channels the loss of Caldendrin mediated synapto-dendritic Ca²⁺-signaling processes in some neurons together with its concurrent upregulation in others should profoundly change their synapto-dendritic Ca²⁺-signaling. These observations add to existing evidence for a de-regulation of neuronal Ca²⁺-signaling in schizophrenia.