title: Astrocytic adenosine 5'-triphosphate release regulates the proliferation of neural stem cells in the adult hippocampus.
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.
authors: Department of Neurobiology, School of Basic Medical Sciences; Key Laboratory of Neuroplasticity of Guangdong Higher Education Institutes, and; School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.
authors: Xiong
authors: X
authors: Cao
authors: Liang-Ping
authors: LP
authors: Li
authors: Xi-He
authors: XH
authors: Qin
authors: Shu-Ji
authors: SJ
authors: Li
authors: Meng
authors: M
authors: Zhang
authors: Qian
authors: Q
authors: Wang
authors: Hong-Hai
authors: HH
authors: Hu
authors: Ying-Ying
authors: YY
authors: Fang
authors: Yu-Bo
authors: YB
authors: Gao
authors: Xiao-Wen
authors: XW
authors: Li
authors: Li-Rong
authors: LR
authors: Sun
authors: Wen-Chao
authors: WC
authors: Xiong
authors: Tian-Ming
authors: TM
authors: Gao
authors: Xin-Hong
authors: XH
authors: Zhu
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D048708:Cell Growth Processes / Q000502:physiology; D006624:Hippocampus / Q000166:cytology* / Q000378:metabolism*; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000172:deficiency / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D058953:Neural Stem Cells / Q000378:metabolism*; D055495:Neurogenesis; D015398:Signal Transduction
chemical_list: D053496:Inositol 1,4,5-Trisphosphate Receptors; D000255:Adenosine Triphosphate
keywords: Adenosine 5′-triphosphate; Adult hippocampal neurogenesis; Astrocyte; Neural stem cells; Proliferative factor