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成年大鼠局灶性损伤后齿状回的功能恢复伴随着结构重组。

Functional recovery of the dentate gyrus after a focal lesion is accompanied by structural reorganization in the adult rat.

机构信息

Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, AP 70-228, 04510, México, D.F., México.

出版信息

Brain Struct Funct. 2013 Mar;218(2):437-53. doi: 10.1007/s00429-012-0407-4. Epub 2012 Apr 6.

Abstract

The adult brain is highly plastic and tends to undergo substantial reorganization after injury to compensate for the lesion effects. It has been shown that such reorganization mainly relies on anatomical and biochemical modifications of the remaining cells which give rise to a network rewiring without reinstating the original morphology of the damaged region. However, few studies have analyzed the neurorepair potential of a neurogenic structure. Thus, the aim of this work was to analyze if the DG could restore its original morphology after a lesion and to establish if the structural reorganization is accompanied by behavioral and electrophysiological recovery. Using a subepileptogenic injection of kainic acid (KA), we induced a focal lesion in the DG and assessed in time (1) the loss and recovery of dependent and non dependent DG cognitive functions, (2) the anatomical reorganization of the DG using a stereological probe and immunohistochemical markers for different neuronal maturation stages and, (3) synaptic plasticity as assessed through the induction of in vivo long-term potentiation (LTP) in the mossy fiber pathway (CA3-DG). Our results show that a DG focal lesion with KA leads to a well delimited region of neuronal loss, disorganization of the structure, the loss of associated mnemonic functions and the impairment to elicit LTP. However, behavioral and synaptic plasticity expression occurs in a time dependent fashion and occurs along the morphological restoration of the DG. These results provide novel information on neural plasticity events associated to functional reorganization after damage.

摘要

成年人大脑具有高度的可塑性,在受伤后往往会经历大量的重组,以补偿损伤的影响。已经表明,这种重组主要依赖于剩余细胞的解剖和生化修饰,从而导致网络重新布线,而不会恢复受损区域的原始形态。然而,很少有研究分析过神经发生结构的神经修复潜力。因此,本工作的目的是分析 DG 是否能在损伤后恢复其原始形态,并确定结构重组是否伴随着行为和电生理恢复。我们使用亚癫痫发作剂量的海人酸(KA)进行注射,在 DG 中诱导了一个局灶性损伤,并在时间上进行了以下评估:(1)依赖和非依赖 DG 认知功能的丧失和恢复;(2)使用立体学探针和不同神经元成熟阶段的免疫组织化学标记物评估 DG 的解剖结构重组;(3)通过在苔藓纤维通路(CA3-DG)中诱导体内长时程增强(LTP)来评估突触可塑性。我们的结果表明,KA 诱导的 DG 局灶性损伤会导致神经元丢失的界限分明区域、结构紊乱、与记忆相关的功能丧失以及无法引发 LTP。然而,行为和突触可塑性的表达是随时间发生的,并与 DG 的形态恢复同时发生。这些结果提供了关于损伤后与功能重组相关的神经可塑性事件的新信息。

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