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Fluoxetine Enhances Neurogenesis in Aged Rats with Cortical Infarcts, but This is not Reflected in a Behavioral Recovery

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Abstract

Age is associated with poor outcome and impaired functional recovery after stroke. Fluoxetine, which is widely used in clinical practice, can regulate hippocampal neurogenesis in young rodents. As the rate of neurogenesis is dramatically reduced during aging, we studied the effect of post-stroke fluoxetine treatment on neurogenesis in the subventricular zone (SVZ) and subgranular zone (SGZ) of dentate gyrus (DG) and whether this would be associated with any behavioral recovery after the cortical infarct in aged rats. Aged rats were randomly assigned to four groups: sham-operated rats, sham-operated rats treated with fluoxetine, rats subjected to cerebral ischemia, and rats with ischemia treated with fluoxetine. Focal cortical ischemia was induced by intracranial injection of vasoconstrictive peptide, endothelin-1 (ET-1). Fluoxetine was administered in the drinking water for 3 weeks starting 1 week after ischemia at a dose of 18 mg/kg/day. Behavioral recovery was evaluated on post-stroke days 29 to 31 after which the survival rate and fate of proliferating cells in the SVZ and DG were assessed by immunohistochemistry. Apoptosis was measured with the TUNEL assay. The results indicated that chronic fluoxetine treatment after stroke enhanced the proliferation of newborn neurons in the SVZ, but not in SGZ, and it suppressed perilesional apoptosis. Fluoxetine treatment did not affect the survival or differentiation of newly generated cells in the SVZ i.e., the enhanced neurogenesis was not translated into a behavioral outcome.

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Acknowledgments

This study was supported by the National Natural Science Foundation of China (No. 81372104, No. 30872736), Program for Liaoning Excellent Talents in University (No. LR2013039) and the Research Fund for the Doctoral Program of Higher Education of China (No. 20112104110003).

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Authors and Affiliations

  1. Neurology, The First Hospital of China Medical University, No.155, North Nan**g Street, He** District, Shenyang, Liaoning, 110001, China

    **aoyu Sun, Zhike Zhou, Tingting Liu, Shanshan Zhao & Chuansheng Zhao

  2. Cardiology, Sheng**g Hospital of China Medical University, Shenyang, China

    Mei Zhao

  3. Dermatology, The First Hospital of China Medical University, Shenyang, China

    Ting **ao

  4. Key Laboratory of Immunodermatology, Ministry of Health, Ministry of Education, Shenyang, China

    Ting **ao

  5. Institute of Clinical Medicine – Neurology, University of Eastern Finland, P. O. Box 1627, 70211, Kuopio, Finland

    Jukka Jolkkonen

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  1. **aoyu Sun
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  2. Zhike Zhou
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  4. Mei Zhao
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  8. Chuansheng Zhao
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Correspondence to Chuansheng Zhao.

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The authors declare that they have no competing interests.

Ethical Approval

The experiments were performed in conformity with the Use Committee of China Medical University [No.: SCXK (Liao) 2008–0005] and were approved by the Institutional Animal Care.

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Sun, X., Zhou, Z., Liu, T. et al. Fluoxetine Enhances Neurogenesis in Aged Rats with Cortical Infarcts, but This is not Reflected in a Behavioral Recovery. J Mol Neurosci 58, 233–242 (2016). https://doi.org/10.1007/s12031-015-0662-y

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