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Olanzapine and S100 Proteins


In their recent paper, Fatemi et al (2006) reported on differential gene expression in the frontal cortex of rats chronically treated with olanzapine. They noted that two genes from the family of S100 proteins, S100A8 and S100A9, were significantly upregulated by olanzapine; S100A8 was increased at least twofold and S100A9 fourfold. Olanzapine is typically used to treat schizophrenia, bipolar disorder, and some forms of depression. Interestingly, it was recently suggested that an upregulation of S100 proteins might be common to antidepressant treatments (Manev and Manev, 2006).

The S100 protein family, which comprises 19 members, most of which are expressed in the brain (Donato, 1999), has been studied for its putative role in neurodegeneration (Businaro et al, 2006) and depression (Hetzel et al, 2005). A report by Whitaker-Azmitia et al (1993) pointed to a link between antidepressants and the glia release of S100B protein. Antidepressants were also shown to be capable of increasing the expression of S100B (Akhisaroglu et al, 2003). Subsequently, it was found that S100A10 protein content is lower in the postmortem brain of depressed subjects compared to samples from nondepressed controls, whereas experimental animals treated with antidepressants had elevated brain levels of S100A10 (Svenningsson et al, 2006).

The new information published by Fatemi et al (2006) provides additional impetus to research the putative role of S100 proteins in the pathobiology of neuropsychiatric disorders and in the mechanisms of action of psychotropic drugs.


  1. Akhisaroglu M, Manev R, Akhisaroglu E, Uz T, Manev H (2003). Both aging and chronic fluoxetine increase S100B content in the mouse hippocampus. Neuroreport 14: 1471–1473.

    CAS  Article  Google Scholar 

  2. Businaro R, Leone S, Fabrizi C, Sorci G, Donato R, Lauro GM et al (2006). S100B protects LAN-5 neuroblastoma cells against Abeta amyloid-induced neurotoxicity via RAGE engagement at low doses but increases Abeta amyloid neurotoxicity at high doses. J Neurosci Res 83: 897–906.

    CAS  Article  Google Scholar 

  3. Donato R (1999). Functional roles of S100 proteins, calcium-binding proteins of the EF-hand type. Biochim Biophys Acta 1450: 191–231.

    CAS  Article  Google Scholar 

  4. Fatemi SH, Reutiman TJ, Folsom TD, Bell C, Nos L, Fried P et al (2006). Chronic olanzapine treatment causes differential expression of genes in frontal cortex of rats as revealed by DNA microarray technique. Neuropsychopharmacology [E-pub ahead of print].

  5. Hetzel G, Moeller O, Evers S, Erfurth A, Ponath G, Arolt V et al (2005). The astroglial protein S100B and visually evoked event-related potentials before and after antidepressant treatment. Psychopharmacol (Berlin) 178: 161–166.

    CAS  Article  Google Scholar 

  6. Manev H, Manev R (2006). Nomen est Omen: do antidepressants increase p11 or S100A10? J Biomed Discov Collab 1: 5.

    Article  Google Scholar 

  7. Svenningsson P, Chergui K, Rachleff I, Flajolet M, Zhang X, Yacoubi ME et al (2006). Alterations in 5-HT1B receptor function by p11 in depression-like states. Science 311: 77–80.

    CAS  Article  Google Scholar 

  8. Whitaker-Azmitia PM, Clarke C, Azmitia EC (1993). Localization of 5-HT1A receptors to astroglial cells in adult rats: implications for neuronal-glial interactions and psychoactive drug mechanism of action. Synapse 14: 201–205.

    CAS  Article  Google Scholar 

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Correspondence to Hari Manev.

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Manev, H., Manev, R. Olanzapine and S100 Proteins. Neuropsychopharmacol 31, 2567 (2006).

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