A reduced number of cortical neurons show increased Caldendrin protein levels in chronic schizophrenia.
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 Ca(2+)-signaling as a multifunctional regulator of intracellular Ca(2+) 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 Ca(2+)-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 Ca(2+)-channels and Ca(2+)-release channels the loss of Caldendrin mediated synapto-dendritic Ca(2+)-signaling processes in some neurons together with its concurrent upregulation in others should profoundly change their synapto-dendritic Ca(2+)-signaling. These observations add to existing evidence for a de-regulation of neuronal Ca(2+)-signaling in schizophrenia.
Bernstein
Hans-Gert
HG
Department of Psychiatry, Faculty of Medicine, Otto-von-Guericke University, Leipziger Str. 44, 39120 Magdeburg, Germany.
Sahin
Jale
J
Smalla
Karl-Heinz
KH
Gundelfinger
Eckart D
ED
Bogerts
Bernhard
B
Kreutz
Michael R
MR
D000328:Adult; D001344:Autopsy; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D002908:Chronic Disease; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D012559:Schizophrenia / Q000145:classification / Q000378:metabolism* / Q000473:pathology; D012563:Schizophrenia, Paranoid / Q000145:classification / Q000378:metabolism / Q000473:pathology
D002135:Calcium-Binding Proteins; C085577:Ca2+-binding protein-1