Astrocytic Adenosine 5′-Triphosphate Release Regulates the Proliferation of Neural Stem Cells in the Adult Hippocampus

Authors

  • Xiong Cao,

    1. Department of Neurobiology, School of Basic Medical Sciences
    2. Key Laboratory of Neuroplasticity of Guangdong Higher Education Institutes, and
    3. School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China
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  • Liang-Ping Li,

    1. Department of Neurobiology, School of Basic Medical Sciences
    2. Key Laboratory of Neuroplasticity of Guangdong Higher Education Institutes, and
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  • Xi-He Qin,

    1. Department of Neurobiology, School of Basic Medical Sciences
    2. Key Laboratory of Neuroplasticity of Guangdong Higher Education Institutes, and
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  • Shu-Ji Li,

    1. Department of Neurobiology, School of Basic Medical Sciences
    2. Key Laboratory of Neuroplasticity of Guangdong Higher Education Institutes, and
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  • Meng Zhang,

    1. Department of Neurobiology, School of Basic Medical Sciences
    2. Key Laboratory of Neuroplasticity of Guangdong Higher Education Institutes, and
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  • Qian Wang,

    1. Department of Neurobiology, School of Basic Medical Sciences
    2. Key Laboratory of Neuroplasticity of Guangdong Higher Education Institutes, and
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  • Hong-Hai Hu,

    1. Department of Neurobiology, School of Basic Medical Sciences
    2. Key Laboratory of Neuroplasticity of Guangdong Higher Education Institutes, and
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  • Ying-Ying Fang,

    1. Department of Neurobiology, School of Basic Medical Sciences
    2. Key Laboratory of Neuroplasticity of Guangdong Higher Education Institutes, and
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  • Yu-Bo Gao,

    1. Department of Neurobiology, School of Basic Medical Sciences
    2. Key Laboratory of Neuroplasticity of Guangdong Higher Education Institutes, and
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  • Xiao-Wen Li,

    1. Department of Neurobiology, School of Basic Medical Sciences
    2. Key Laboratory of Neuroplasticity of Guangdong Higher Education Institutes, and
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  • Li-Rong Sun,

    1. Department of Neurobiology, School of Basic Medical Sciences
    2. Key Laboratory of Neuroplasticity of Guangdong Higher Education Institutes, and
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  • Wen-Chao Xiong,

    1. Department of Neurobiology, School of Basic Medical Sciences
    2. Key Laboratory of Neuroplasticity of Guangdong Higher Education Institutes, and
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  • Tian-Ming Gao,

    1. Department of Neurobiology, School of Basic Medical Sciences
    2. Key Laboratory of Neuroplasticity of Guangdong Higher Education Institutes, and
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  • Xin-Hong Zhu

    Corresponding author
    1. Department of Neurobiology, School of Basic Medical Sciences
    2. Key Laboratory of Neuroplasticity of Guangdong Higher Education Institutes, and
    3. School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China
    • Department of Neurobiology, Southern Medical University, Guangzhou 510515, China===

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    • Telephone: +86-20-61647112; Fax: +86-20-61647112


  • Author contributions: X.-H.Z. and T.-M.G.: conception and design and financial support; X.C.: performed the experiments; L.-P.L. and S.-J.L.: contributed to the cell culture; X.-H.Q. and Q.W.: performed the immunofluorescence staining and PCR; Y.-Y.F.: performed the stereotaxic microinjections; M.Z., L.-R.S., and W.-C.X.: contributed to the ATP measurements; H.-H.H.: performed the calcium imaging; X.-W.L. and Y.-B.G.: contributed to the animal care and genotyping; X.-H.Z., T.-M.G., and X.C.: manuscript writing and data analysis and interpretation.

Abstract

Astrocytes are key components of the niche for neural stem cells (NSCs) in the adult hippocampus and play a vital role in regulating NSC proliferation and differentiation. However, the exact molecular mechanisms by which astrocytes modulate NSC proliferation have not been identified. Here, we identified adenosine 5′-triphosphate (ATP) as a proliferative factor required for astrocyte-mediated proliferation of NSCs in the adult hippocampus. Our results indicate that ATP is necessary and sufficient for astrocytes to promote NSC proliferation in vitro. The lack of inositol 1,4,5-trisphosphate receptor type 2 and transgenic blockage of vesicular gliotransmission induced deficient ATP release from astrocytes. This deficiency led to a dysfunction in NSC proliferation that could be rescued via the administration of exogenous ATP. Moreover, P2Y1-mediated purinergic signaling is involved in the astrocyte promotion of NSC proliferation. As adult hippocampal neurogenesis is potentially involved in major mood disorder, our results might offer mechanistic insights into this disease. STEM Cells 2013;31:1633–1643

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