Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, AP 70-228, 04510, Mexico, DF, Mexico.
Brain Struct Funct. 2018 Jul;223(6):2859-2877. doi: 10.1007/s00429-018-1664-7. Epub 2018 Apr 16.
The dentate gyrus (DG) is a neurogenic structure that exhibits functional and structural reorganization after injury. Neurogenesis and functional recovery occur after brain damage, and the possible relation between both processes is a matter of study. We explored whether neurogenesis and the activation of new neurons correlated with DG recovery over time. We induced a DG lesion in young adult rats through the intrahippocampal injection of kainic acid and analyzed functional recovery and the activation of new neurons after animals performed a contextual fear memory task (CFM) or a control spatial exploratory task. We analyzed the number of BrdU+ cells that co-localized with doublecortin (DCX) or with NeuN within the damaged DG and evaluated the number of cells in each population that were labelled with the activity marker c-fos after either task. At 10 days post-lesion (dpl), a region of the granular cell layer was devoid of cells, evidencing the damaged area, whereas at 30 dpl this region was significantly smaller. At 10 dpl, the number of BrdU+/DCX+/c-fos positive cells was increased compared to the sham-lesion group, but CFM was impaired. At 30 dpl, a significantly greater number of BrdU+/NeuN+/c-fos positive cells was observed than at 10 dpl, and activation correlated with CFM recovery. Performance in the spatial exploratory task induced marginal c-fos immunoreactivity in the BrdU+/NeuN+ population. We demonstrate that neurons born after the DG was damaged survive and are activated in a time- and task-dependent manner and that activation of new neurons occurs along functional recovery.
齿状回(DG)是一种具有神经发生功能的结构,在损伤后会发生功能和结构的重组。脑损伤后会发生神经发生和功能恢复,这两个过程之间的可能关系是研究的课题。我们探讨了神经发生和新神经元的激活是否与 DG 的随时间恢复相关。我们通过在海马内注射海人酸诱导年轻成年大鼠的 DG 损伤,并在动物执行情景恐惧记忆任务(CFM)或对照空间探索任务后分析 DG 的功能恢复和新神经元的激活。我们分析了在损伤的 DG 内与双皮质素(DCX)或神经元核抗原(NeuN)共定位的 BrdU+细胞的数量,并评估了在完成任一项任务后,用活性标志物 c-fos 标记的每个细胞群体中的细胞数量。在损伤后 10 天(dpl),颗粒细胞层的一个区域没有细胞,表明这是受损区域,而在 30 dpl 时,该区域明显缩小。在 10 dpl 时,与假手术组相比,BrdU+/DCX+/c-fos 阳性细胞的数量增加,但 CFM 受损。在 30 dpl 时,与 10 dpl 相比,BrdU+/NeuN+/c-fos 阳性细胞的数量显著增加,并且激活与 CFM 的恢复相关。在空间探索任务中,BrdU+/NeuN+群体中的 c-fos 免疫反应性略有增加。我们证明,在 DG 受损后产生的神经元存活并以时间和任务依赖的方式被激活,并且新神经元的激活发生在功能恢复的过程中。