A consequence of immature breathing induces persistent changes in hippocampal synaptic plasticity and behavior: a role of prooxidant state and NMDA receptor imbalance.
A consequence of immature breathing induces persistent changes in hippocampal synaptic plasticity and behavior: a role of prooxidant state and NMDA receptor imbalance.
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未成熟呼吸的结果引起了海马突触可塑性和行为的持续变化：促氧化剂状态和NMDA受体失衡的作用。
DOI：
10.3389/fnmol.2023.1192833
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发表时间：
2023
影响因子：
4.8
通讯作者：
Garcia III, Alfredo J. J.
中科院分区：
文献类型：
--
作者：
Arias-Cavieres, Alejandra;Garcia III, Alfredo J. J.
早产导致呼吸不发达，并在新生儿早期引起间歇性缺氧。新生儿间歇性缺氧（nIH）是一种与生命后期神经认知缺陷风险增加有关的疾病。然而，nIH诱导的神经生理学变化的机制基础仍然很难解决。我们研究了nIH对新生小鼠海马突触可塑性和NMDA受体（NMDAr）表达的影响。我们的研究结果表明，nIH诱导促氧化状态，导致NMDAr亚基组成失衡，有利于GluN 2B而不是GluN 2A表达，并损害突触可塑性。这些后果持续到成年期，并与空间记忆的缺陷相吻合。治疗与抗氧化剂，锰（III）四（1-甲基-4-吡啶基）卟啉（MnTMPyP），在nIH有效地减轻了nIH的即时和长期影响。然而，MnTMPyP治疗后nIH没有阻止突触可塑性或行为的长期变化。除了证明促氧化剂状态在nIH介导的神经生理和行为缺陷中具有核心作用外，我们的研究结果还表明，在离散治疗窗口期间靶向促氧化剂状态可能为减轻出生后早期呼吸不稳定导致的长期神经生理和行为结果提供潜在途径。
Underdeveloped breathing results from premature birth and causes intermittent hypoxia during the early neonatal period. Neonatal intermittent hypoxia (nIH) is a condition linked to the increased risk of neurocognitive deficit later in life. However, the mechanistic basis of nIH-induced changes to neurophysiology remains poorly resolved. We investigated the impact of nIH on hippocampal synaptic plasticity and NMDA receptor (NMDAr) expression in neonatal mice. Our findings indicate that nIH induces a prooxidant state that leads to an imbalance in NMDAr subunit composition favoring GluN2B over GluN2A expression and impairs synaptic plasticity. These consequences persist in adulthood and coincide with deficits in spatial memory. Treatment with an antioxidant, manganese (III) tetrakis (1-methyl-4-pyridyl)porphyrin (MnTMPyP), during nIH effectively mitigated both immediate and long-term effects of nIH. However, MnTMPyP treatment post-nIH did not prevent long-lasting changes in either synaptic plasticity or behavior. In addition to demonstrating that the prooxidant state has a central role in nIH-mediated neurophysiological and behavioral deficits, our results also indicate that targeting the prooxidant state during a discrete therapeutic window may provide a potential avenue for mitigating long-term neurophysiological and behavioral outcomes that result from unstable breathing during early postnatal life.
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