Brain and Spinal Injury Center, San Francisco General Hospital, University of California at San Francisco San Francisco, CA, USA ; Department of Physical Therapy and Rehabilitation Science, University of California at San Francisco San Francisco, CA, USA.
Front Cell Neurosci. 2013 Sep 6;7:145. doi: 10.3389/fncel.2013.00145.
Throughout life new neurons are continuously added to the hippocampal circuitry involved with spatial learning and memory. These new cells originate from neural precursors in the subgranular zone of the dentate gyrus, migrate into the granule cell layer, and integrate into neural networks encoding spatial and contextual information. This process can be influenced by several environmental and endogenous factors and is modified in different animal models of neurological disorders. Neuroinflammation, as defined by the presence of activated microglia, is a common key factor to the progression of neurological disorders. Analysis of the literature shows that microglial activation impacts not only the production, but also the migration and the recruitment of new neurons. The impact of microglia on adult-born neurons appears much more multifaceted than ever envisioned before, combining both supportive and detrimental effects that are dependent upon the activation phenotype and the factors being released. The development of strategies aimed to change microglia toward states that promote functional neurogenesis could therefore offer novel therapeutic opportunities against neurological disorders associated with cognitive deficits and neuroinflammation. The present review summarizes the current knowledge on how production, distribution, and recruitment of new neurons into behaviorally relevant neural networks are modified in the inflamed hippocampus.
在整个生命过程中,新的神经元不断被添加到与空间学习和记忆相关的海马回路中。这些新的细胞来源于齿状回颗粒下区的神经前体细胞,迁移到颗粒细胞层,并整合到编码空间和上下文信息的神经网络中。这个过程可以受到几种环境和内源性因素的影响,并在不同的神经障碍动物模型中被改变。神经炎症,即激活的小胶质细胞的存在,是神经障碍进展的一个共同关键因素。文献分析表明,小胶质细胞的激活不仅影响新神经元的产生,还影响其迁移和募集。小胶质细胞对成年神经元的影响比以前想象的要复杂得多,它结合了支持和有害的作用,这取决于激活表型和释放的因子。因此,开发旨在使小胶质细胞向促进功能性神经发生的状态转变的策略,可能为与认知缺陷和神经炎症相关的神经障碍提供新的治疗机会。本综述总结了目前关于在炎症海马体中,新神经元的产生、分布和募集如何被改变以适应行为相关神经网络的知识。