Hippocampus-prefrontal cortex inputs modulate spatial learning and memory in a mouse model of sepsis induced by cecal ligation puncture.
Hippocampus-prefrontal cortex inputs modulate spatial learning and memory in a mouse model of sepsis induced by cecal ligation puncture.
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海马-前额叶皮层输入调节盲肠结扎穿刺诱发脓毒症小鼠模型的空间学习和记忆
DOI：
10.1111/cns.14013
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发表时间：
2023-01
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
--
作者：
脓毒症相关脑病（SAE）通常会导致认知障碍。然而，SAE的病理生理学复杂且不清楚。在这里，我们研究了海马（HPC）-前额叶皮层（PFC）在盲肠结扎穿刺（CLP）诱导的脓毒症小鼠认知功能障碍中的作用。从HPC到PFC的神经投射首先通过逆行追踪和病毒表达来确定。通过PFC中c-Fos-阳性神经元的免疫荧光染色显示HPC-PFC通路的化学发生激活。使用Morris水迷宫（MWM）和巴恩斯迷宫（BM）评估认知功能。采用Western blotting法检测PFC和HPC中谷氨酸受体及相关分子的表达。HPC-PFC通路的化学发生激活增强了CLP诱导的脓毒症小鼠的认知功能障碍。谷氨酸受体介导CLP小鼠中HPC‐PFC通路激活的效应。HPC-PFC通路的激活导致PFC中NMDAR、AMPAR和下游信号分子（包括CaMKIIa、pCREB和BDNF）的水平显著增加。然而，使用α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体2，3-二羟基-6-硝基-7-氨磺酰基-苯并（F）喹喔啉（NBQX）抑制谷氨酸受体，（AMPAR抑制剂）或D-2-氨基-5-膦酰基戊酸酯（D-AP 5）（其是NMDA受体拮抗剂）消除了这种增加。我们的研究揭示了HPC-PFC途径在改善CLP脓毒症小鼠模型中认知功能障碍方面的重要作用，并为SAE提供了一种新的发病机制。脓毒症相关脑病的拟定机制。HPC‐PFC通路在脓毒症相关脑病（SAE）的认知功能障碍中起重要作用。具体而言，谷氨酸受体介导的下游信号传导中的CaMKII/CREB/BDNF通路似乎是连接HPC‐mPFC通路与SAE中空间记忆受损的重要分子机制。
Sepsis‐associated encephalopathy (SAE) often leads to cognitive impairments. However, the pathophysiology of SAE is complex and unclear. Here, we investigated the role of hippocampus (HPC)‐prefrontal cortex (PFC) in cognitive dysfunction in sepsis induced by cecal ligation puncture (CLP) in mice. The neural projections from the HPC to PFC were first identified via retrograde tracing and viral expression. Chemogenetic activation of the HPC‐PFC pathway was shown via immunofluorescent staining of c‐Fos‐positive neurons in PFC. Morris Water Maze (MWM) and Barnes maze (BM) were used to evaluate cognitive function. Western blotting analysis was used to determine the expression of glutamate receptors and related molecules in PFC and HPC. Chemogenetic activation of the HPC‐PFC pathway enhanced cognitive dysfunction in CLP‐induced septic mice. Glutamate receptors mediated the effects of HPC‐PFC pathway activation in CLP mice. The activation of the HPC‐PFC pathway resulted in significantly increased levels of NMDAR, AMPAR, and downstream signaling molecules including CaMKIIa, pCREB, and BDNF in PFC. However, inhibition of glutamate receptors using 2,3‐dihydroxy‐6‐nitro‐7‐sulphamoyl‐benzo (F)quinoxaline (NBQX), which is an α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptor (AMPAR inhibitor), or D‐2‐amino‐5‐phosphonopentanoate (D‐AP5), which is an NMDA receptor antagonist abolished this increase. Our study reveals the important role of the HPC‐PFC pathway in improving cognitive dysfunction in a mouse model of CLP sepsis and provides a novel pathogenetic mechanism for SAE. The proposed mechanism of sepsis‐associated encephalopathy. HPC‐PFC pathway plays an important role in cognitive dysfunction in sepsis‐associated encephalopathy (SAE). Specifically, CaMKII/CREB/BDNF pathway in the glutamate receptor‐mediated downstream signaling appears to be an important molecular mechanism linking the HPC‐mPFC pathway with impairing spatial memory in SAE.
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影响因子：
34.7
作者：
Lisman, John;Yasuda, Ryohei;Raghavachari, Sridhar
通讯作者：
Raghavachari, Sridhar
影响因子：
5.3
作者：
Liu, Jianfeng;Wu, Ruyan;Li, Jun-Xu
通讯作者：
Li, Jun-Xu
DOI：
10.1038/nri3552
发表时间：
2013-12
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1177/0271678x21999553
发表时间：
2021-09
期刊：
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
影响因子：
--
作者：
Chandra PK;Cikic S;Baddoo MC;Rutkai I;Guidry JJ;Flemington EK;Katakam PV;Busija DW
通讯作者：
Busija DW
影响因子：
5.7
作者：
Chavan, Sangeeta S.;Huerta, Patricio T.;Diamond, Betty
通讯作者：
Diamond, Betty