Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, Rockefeller University, New York, USA.
Hippocampus. 2011 Mar;21(3):253-64. doi: 10.1002/hipo.20744.
Chronic restraint stress (CRS) induces the remodeling (i.e., retraction and simplification) of the apical dendrites of hippocampal CA3 pyramidal neurons in rats, suggesting that intrahippocampal connectivity can be affected by a prolonged stressful challenge. Since the structural maintenance of neuronal dendritic arborizations and synaptic connectivity requires neurotrophic support, we investigated the potential role of brain derived neurotrophic factor (BDNF), a neurotrophin enriched in the hippocampus and released from neurons in an activity-dependent manner, as a mediator of the stress-induced dendritic remodeling. The analysis of Golgi-impregnated hippocampal sections revealed that wild type (WT) C57BL/6 male mice showed a similar CA3 apical dendritic remodeling in response to three weeks of CRS to that previously described for rats. Haploinsufficient BDNF mice (BDNF(±) ) did not show such remodeling, but, even without CRS, they presented shorter and simplified CA3 apical dendritic arbors, like those observed in stressed WT mice. Furthermore, unstressed BDNF(±) mice showed a significant decrease in total hippocampal volume. The dendritic arborization of CA1 pyramidal neurons was not affected by CRS or genotype. However, only in WT mice, CRS induced changes in the density of dendritic spine shape subtypes in both CA1 and CA3 apical dendrites. These results suggest a complex role of BDNF in maintaining the dendritic and spine morphology of hippocampal neurons and the associated volume of the hippocampal formation. The inability of CRS to modify the dendritic structure of CA3 pyramidal neurons in BDNF(±) mice suggests an indirect, perhaps permissive, role of BDNF in mediating hippocampal dendritic remodeling.
慢性束缚应激（CRS）可诱导大鼠海马 CA3 锥体神经元树突的重塑（即回缩和简化），表明海马内连接可以受到长期应激挑战的影响。由于神经元树突分支和突触连接的结构维持需要神经营养支持，我们研究了脑源性神经营养因子（BDNF）的潜在作用，BDNF 是一种富含海马的神经营养因子，以活性依赖的方式从神经元中释放，作为应激诱导树突重塑的介质。高尔基浸渍海马切片的分析表明，野生型（WT）C57BL/6 雄性小鼠在三周的 CRS 后表现出与以前在大鼠中描述的相似的 CA3 顶树突重塑。BDNF 部分缺失（BDNF(±)）小鼠没有表现出这种重塑，但即使没有 CRS，它们也表现出更短和简化的 CA3 顶树突分支，类似于应激 WT 小鼠中观察到的。此外，未应激的 BDNF(±)小鼠的海马总体积显著减少。CA1 锥体神经元的树突分支不受 CRS 或基因型的影响。然而，只有在 WT 小鼠中，CRS 诱导了 CA1 和 CA3 顶树突中树突棘形状亚型密度的变化。这些结果表明 BDNF 在维持海马神经元的树突和棘形态以及海马结构的相关体积方面具有复杂的作用。CRS 不能改变 BDNF(±)小鼠 CA3 锥体神经元的树突结构表明 BDNF 在介导海马树突重塑中具有间接的、可能是许可的作用。
