Disrupted Neuroglial Metabolic Coupling after Peripheral Surgery
Disrupted Neuroglial Metabolic Coupling after Peripheral Surgery
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DOI：
10.1523/jneurosci.1797-17.2017
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发表时间：
2018-01-10
影响因子：
5.3
通讯作者：
Gomez-Galan, Marta
中科院分区：
文献类型：
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作者：
Femenia, Teresa;Gimenez-Cassina, Alfredo;Gomez-Galan, Marta
周围的免疫相关事件可以远程影响大脑功能，导致神经退行性过程和认知能力下降。在小鼠中，外周手术会诱发与海马突触可塑性变化和短暂认知能力下降相关的全身炎症反应，但其潜在机制仍不清楚。在这里，我们研究了外周手术对雄性小鼠术后 6、24 和 72 小时海马神经元回路内与认知处理相关的神经元胶质功能的影响。 6 小时后，我们检测到海马中的促炎细胞因子 IL-6，随后星形胶质细胞和神经元蛋白的 mRNA 和蛋白表达发生变化，这些变化是大脑最佳能量供应以及突触中谷氨酸的再摄取和循环所必需的。同样，术后 24 小时，结构蛋白（GFAP 和 AQP4）的 mRNA 表达受到影响。此时，星形胶质细胞的功能分析显示静息钙信号传导减少。通过全细胞膜片钳检查神经元活动显示术后 72 小时谷氨酸能传递水平升高和 AMPA 受体亚基组成发生变化。最后，乳酸（一种由星形胶质细胞产生的必需能量底物，对记忆形成至关重要）会在术后 6 小时和 72 小时下降。基于与我们之前研究的时间相似性，我们提出，先前报道的小鼠术后 72 小时观察到的认知能力下降可能是星形胶质细胞颞海马代谢、结构和功能变化的结果，导致神经胶质代谢耦合破坏，从而导致神经元功能障碍。
Immune-related events in the periphery can remotely affect brain function, contributing to neurodegenerative processes and cognitive decline. In mice, peripheral surgery induces a systemic inflammatory response associated with changes in hippocampal synaptic plasticity and transient cognitive decline, however, the underlying mechanisms remain unknown. Here we investigated the effect of peripheral surgery on neuronal-glial function within hippocampal neuronal circuits of relevance to cognitive processing in male mice at 6, 24, and 72 h postsurgery. At 6 h we detect the proinflammatory cytokine IL-6 in the hippocampus, followed up by alterations in the mRNA and protein expression of astrocytic and neuronal proteins necessary for optimal energy supply to the brain and for the reuptake and recycling of glutamate in the synapse. Similarly, at 24 h postsurgery the mRNA expression of structural proteins (GFAP and AQP4) was compromised. At this time point, functional analysis in astrocytes revealed a decrease in resting calcium signaling. Examination of neuronal activity by whole-cell patch-clamp shows elevated levels of glutamatergic transmission and changes in AMPA receptor subunit composition at 72 h postsurgery. Finally, lactate, an essential energy substrate produced by astrocytes and critical for memory formation, decreases at 6 and 72 h after surgery. Based on temporal parallels with our previous studies, we propose that the previously reported cognitive decline observed at 72 h postsurgery in mice might be the consequence of temporal hippocampal metabolic, structural, and functional changes in astrocytes that lead to a disruption of the neuroglial metabolic coupling and consequently to a neuronal dysfunction.