Ali Amira A H, Abdel-Hafiz Laila, Tundo-Lavalle Federica, Hassan Soha A, von Gall Charlotte
Institute of Anatomy II, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine-University, Düsseldorf, Germany.
Zoology Department, Faculty of Science, Suez University, Suez, Egypt.
FASEB J. 2021 May;35(5):e21546. doi: 10.1096/fj.202002419RR.
Adult neurogenesis occurs particularly in the subgranular zone (SGZ) of the hippocampus and the subventricular zone (SVZ) of the lateral ventricle. This continuous addition of neurons to pre-existing neuronal networks is essential for intact cognitive and olfactory functions, respectively. Purinergic signaling modulates adult neurogenesis, however, the role of individual purinergic receptor subtypes in this dynamic process and related cognitive performance is poorly understood. In this study, we analyzed the role of P2Y receptor in the neurogenic niches and in related forebrain functions such as spatial working memory and olfaction using mice with a targeted deletion of the P2Y receptor (P2Y2 ). Proliferation, migration, differentiation, and survival of neuronal precursor cells (NPCs) were analyzed by BrdU assay and immunohistochemistry; signal transduction pathway components were analyzed by immunoblot. In P2Y2 mice, proliferation of NPCs in the SGZ and the SVZ was reduced. However, migration, neuronal fate decision, and survival were not affected. Moreover, p-Akt expression was decreased in P2Y2 mice. P2Y2 mice showed an impaired performance in the Y-maze and a higher latency in the hidden food test. These data indicate that the P2Y receptor plays an important role in NPC proliferation as well as in hippocampus-dependent working memory and olfactory function.
成体神经发生尤其发生在海马体的颗粒下区（SGZ）和侧脑室的室下区（SVZ）。这种向已有的神经元网络持续添加神经元的过程分别对于完整的认知功能和嗅觉功能至关重要。嘌呤能信号传导调节成体神经发生，然而，单个嘌呤能受体亚型在这个动态过程及相关认知表现中的作用却知之甚少。在本研究中，我们使用P2Y受体（P2Y2）靶向缺失的小鼠，分析了P2Y受体在神经发生微环境以及相关的前脑功能（如空间工作记忆和嗅觉）中的作用。通过BrdU检测和免疫组织化学分析神经元前体细胞（NPCs）的增殖、迁移、分化和存活情况；通过免疫印迹分析信号转导通路成分。在P2Y2基因敲除小鼠中，SGZ和SVZ中NPCs的增殖减少。然而，迁移、神经元命运决定和存活不受影响。此外，P2Y2基因敲除小鼠中p-Akt表达降低。P2Y2基因敲除小鼠在Y迷宫实验中表现受损，在隐藏食物测试中潜伏期更长。这些数据表明，P2Y受体在NPC增殖以及海马体依赖的工作记忆和嗅觉功能中发挥重要作用。
