Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho Braga, Portugal ; ICVS/3B's - PT Government Associate Laboratory Braga/Guimarães, Portugal.
Front Cell Neurosci. 2013 Jul 29;7:122. doi: 10.3389/fncel.2013.00122. eCollection 2013.
Lipocalin-2 (LCN2), an iron-related protein well described to participate in the innate immune response, has been shown to modulate spine morphology and to regulate neuronal excitability. In accordance, LCN2-null mice are reported to have stress-induced anxiety. Here we show that, under standard housing conditions, LCN2-null mice display anxious and depressive-like behaviors, as well as cognitive impairment in spatial learning tasks. These behavioral alterations were associated with a hyperactivation of the hypothalamic-pituitary-adrenal axis and with an altered brain cytoarchitecture in the hippocampus. More specifically, we found that the granular and pyramidal neurons of the ventral hippocampus, a region described to be associated with emotion, were hypertrophic, while neurons from the dorsal hippocampus, a region implicated in memory and cognition, were atrophic. In addition, LCN2-null mice presented synaptic impairment in hippocampal long-term potentiation. Whether the LCN2 effects are mediated through modulation of the level of corticosteroids or through a novel mechanism, the present observations bring further into light this immune-related protein as a player in the fine-tuning of behavior and of synaptic activity.
脂联素 2（LCN2）是一种与铁相关的蛋白，其在先天免疫反应中的作用已得到充分描述，它被证明可以调节脊柱形态并调节神经元兴奋性。因此，LCN2 缺失小鼠表现出应激诱导的焦虑。在这里，我们发现，在标准饲养条件下，LCN2 缺失小鼠表现出焦虑和抑郁样行为，以及在空间学习任务中认知受损。这些行为改变与下丘脑-垂体-肾上腺轴的过度激活以及海马体中脑结构的改变有关。更具体地说，我们发现腹侧海马体（与情绪相关的区域）的颗粒细胞和锥体细胞发生了肥大，而背侧海马体（与记忆和认知有关的区域）的神经元则发生了萎缩。此外，LCN2 缺失小鼠在海马体长时程增强中出现了突触损伤。LCN2 的作用是通过调节皮质酮水平还是通过新的机制来介导的，目前的观察结果进一步揭示了这种免疫相关蛋白在行为和突触活动的微调中的作用。
