Suppression of mPFC‐Amygdala Circuit Mitigates Sevoflurane‐Induced Cognitive Deficits in Aged Mice

作者：Junhua Li, Jin Wen, Meigu Zeng, Jinghong Mei, Cong Zeng, Ning Liufu, Yujuan Li · 发表于：CNS Neuroscience & Therapeutics · 年份：2025 · DOI：10.1111/cns.70443 · 被引用次数：5 · 研究领域：Intensive Care Unit Cognitive Disorders、Anesthesia and Neurotoxicity Research、Anesthesia and Sedative Agents

BACKGROUND: Perioperative neurocognitive disorders (PND) are common and costly complications in elderly surgical patients, yet the involvement of specific neural circuits in their etiology remains poorly understood. We hypothesized that neural projections from the medial prefrontal cortex (mPFC) to the amygdala contribute to PND pathogenesis. METHODS: Using chemogenetic approaches, we selectively suppressed or excited the mPFC and its projections to the amygdala in a murine model exposed to sevoflurane. We assessed cognitive deficits, synaptic plasticity (AMPA receptor activity, long-term potentiation [LTP]), mitochondrial stress, neuroinflammatory markers, and neuronal apoptosis in the amygdala. Additional interventions included pharmacological suppression of AMPA receptors, glutamate biosynthesis, and mitochondrial stress within the amygdala. RESULTS: Sevoflurane exposure activated the mPFC-amygdala circuit. Chemogenetic suppression of the mPFC attenuated sevoflurane-induced cognitive deficits, AMPA receptor hyperexcitation, mitochondrial dysfunction, neuroinflammation, and neuronal apoptosis in the amygdala. Retrograde inhibition of mPFC projections to the amygdala alleviated cognitive impairments, whereas retrograde excitation exacerbated them. Suppressing AMPA receptors, glutamate synthesis, or mitochondrial stress in the amygdala similarly reduced cognitive deficits and pathological alterations. Notably, mPFC suppression rescued sevoflurane-induced LTP impairment in the...