Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023
Anesthesia-induced hippocampal-cortical hyperactivity and tau hyperphosphorylation impair remote memory retrieval in Alzheimer's disease.
СтатьяПоддержка исследования: вне правительства СШАПоддержка NIH: внешняя программаНазвание и аннотация: Перевод в очереди
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Chen Kai, Gupta Riya, Martín-Ávila Alejandro, Cui Meng, Xie Zhongcong, Yang Guang
Аннотация
INTRODUCTION: Anesthesia often exacerbates memory recall difficulties in individuals with Alzheimer's disease (AD), but the underlying mechanisms remain unclear.
METHODS: We used in vivo Ca2+ imaging, viral-based circuit tracing, and chemogenetic approaches to investigate anesthesia-induced remote memory impairment in mouse models of presymptomatic AD.
RESULTS: 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.
DISCUSSION: 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.
METHODS: We used in vivo Ca2+ imaging, viral-based circuit tracing, and chemogenetic approaches to investigate anesthesia-induced remote memory impairment in mouse models of presymptomatic AD.
RESULTS: 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.
DISCUSSION: 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.