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Cell Type-Specific Gene Expression and Editing Responses to Chronic Fluoxetine Treatment in the In Vivo Mouse Brain and Their Relevance for Stress-Induced Anhedonia

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Abstract

Recently developed methods for fluorescence-activated cell sorting (FACS) of freshly-isolated brain cells from transgenic mice combining fluorescent signals with cell type-specific markers allow cell-type separation. Based upon previous observations in primary cultures of mouse astrocytes we treated transgenic mice tagged with a neuron-specific or an astrocyte-specific marker with fluoxetine, either acute (10 mg/kg for 2 h) or chronic (10 mg/kg daily for 2 weeks). Acute treatment upregulated cfos and fosB mRNA expression in astrocytes and neurons. Chronic effects on astrocytes replicated those demonstrated in cultures, i.e., upregulation of mRNA and/or protein expression of 5-HT2B receptors (5-HT2BR), and GluK2 receptors, and of cPLA2a and ADAR2, together with increased GluK2 and 5-HT2BR editing. Neurons showed increased GluK4 and 5-HT2C receptor expression. To further correlate these findings with major depression we compared the changes in gene expression with those in a mouse model of anhedonia. Three out of 4 genes up-regulated in astrocytes by fluoxetine were down-regulated, whereas the neuronally upregulated 5-HT2C receptor gene showed no change. References are made to recent review papers discussing potential relations between observed fluoxetine effects and clinical effects of SSRIs, emphasizing that all 5 clinically used SSRIs have identical and virtually equipotent effects on cultured astrocytes.

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Acknowledgments

This study was supported by Grants No. 31000479 to BL and No. 30770667 and 31171036 to LP from the National Natural Science Foundation of China.

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The authors report no conflicts of interest.

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Authors and Affiliations

  1. Department of Clinical Pharmacology and Institute of Pathophysiology, China Medical University, No. 92 Beier Road, Heping District, Shenyang, People’s Republic of China

    Baoman Li, Lu Dong, Bing Wang & Liang Peng

  2. Laboratory of Molecular Biology, Liaoning University of Traditional Chinese Medicine, Shenyang, People’s Republic of China

    Liping Cai & Ning Jiang

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  1. Baoman Li
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  2. Lu Dong
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  3. Bing Wang
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  4. Liping Cai
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Correspondence to Baoman Li.

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In Honor of Leif Hertz

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Li, B., Dong, L., Wang, B. et al. Cell Type-Specific Gene Expression and Editing Responses to Chronic Fluoxetine Treatment in the In Vivo Mouse Brain and Their Relevance for Stress-Induced Anhedonia. Neurochem Res 37, 2480–2495 (2012). https://doi.org/10.1007/s11064-012-0814-1

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  • DOI: https://doi.org/10.1007/s11064-012-0814-1

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