Department of Anesthesiology, Columbia University Irving Medical Center, New York, New York, USA.
Barnard College of Columbia University, New York, New York, USA.
Alzheimers Dement. 2024 Jan;20(1):494-510. doi: 10.1002/alz.13464. Epub 2023 Sep 11.
Anesthesia often exacerbates memory recall difficulties in individuals with Alzheimer's disease (AD), but the underlying mechanisms remain unclear.
We used in vivo Ca imaging, viral-based circuit tracing, and chemogenetic approaches to investigate anesthesia-induced remote memory impairment in mouse models of presymptomatic AD.
Our study identified pyramidal neuron hyperactivity in the anterior cingulate cortex (ACC) as a significant contributor to anesthesia-induced remote memory impairment. This ACC hyperactivation arises from the disinhibition of local inhibitory circuits and increased excitatory inputs from the hippocampal CA1 region. Inhibiting hyperactivity in the CA1-ACC circuit improved memory recall after anesthesia. Moreover, anesthesia led to increased tau phosphorylation in the hippocampus, and inhibiting this hyperphosphorylation prevented ACC hyperactivity and subsequent memory impairment.
Hippocampal-cortical hyperactivity plays a role in anesthesia-induced remote memory impairment. Targeting tau hyperphosphorylation shows promise as a therapeutic strategy to mitigate anesthesia-induced neural network dysfunction and retrograde amnesia in AD.
麻醉常使阿尔茨海默病（AD）患者的记忆再现困难加重，但潜在机制仍不清楚。
我们采用活体钙成像、病毒源性回路示踪和化学遗传学方法，研究了 AD 前症小鼠模型中麻醉引起的远期记忆障碍。
我们的研究发现，扣带前皮质（ACC）中的锥体神经元过度活跃是麻醉引起的远期记忆障碍的一个重要原因。这种 ACC 过度兴奋源于局部抑制回路的去抑制和来自海马 CA1 区的兴奋性输入增加。抑制 CA1-ACC 回路的过度兴奋可改善麻醉后的记忆再现。此外，麻醉导致海马区 tau 过度磷酸化，抑制这种过度磷酸化可防止 ACC 过度兴奋和随后的记忆障碍。
海马-皮质过度兴奋在麻醉引起的远期记忆障碍中起作用。靶向 tau 过度磷酸化显示出作为一种治疗策略的潜力，可减轻 AD 中麻醉引起的神经网络功能障碍和逆行性遗忘。
