Anesthesia‐induced hippocampal‐cortical hyperactivity and tau hyperphosphorylation impair remote memory retrieval in Alzheimer's disease
Open accessAbstract
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 Ca 2+ 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.
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Post-anesthesia arousal is associated with hyperactivity in mice.
“Post-anesthesia arousal is associated with hyperactivity in mice11”
From A curious concept of CNS clearance (2025) · cites this paper as [11]
The Discussion (page unavailable) reports increased neuronal activity after sevoflurane anesthesia in presymptomatic Alzheimer’s-model mice, which supports a narrower version of the claim. It does not establish hyperactivity during post-anesthesia arousal: the Results measure neuronal activity the following day and report no significant increase in the mice’s locomotor activity. (LLM, conf=0.86)
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A curious concept of CNS clearance
Plá, V., Kroesbergen, E., Deng, S., Giannetto, M. J., Hablitz, L. M., Newbold, E., Ladrón-de-Guevara, A., Esmail, T., Gomolka, R. S., Mori, Y., et al. (2025) · Nature Neuroscience · doi:10.1038/s41593-025-01897-3 · Cited by 15 · see citing works
- Authors
- Chen, K., Gupta, R., Martín‐Ávila, A., Cui, M., Xie, Z., & Yang, G.
- Affiliations
- Columbia University Irving Medical Center (US)
- Columbia University (US)
- New York University (US)
- Purdue University West Lafayette (US)
- Harvard University (US)
- Corresponding author
- Xie, Zhongcong
- Yang, Guang
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2023-09-11
- Volume
- 20
- Issue
- 1
- Pages
- 494-510
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- PMC
- PMC10843666
- OpenAlex
- W4386592618
- Cited by
- 19
- References
- 5
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 5
- FWCI
- 2.11
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Alzheimer s & Dementia (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (GM131765, AG041274, AG062509, NS118302)
- Alzheimer's Association (AARFD‐17‐533584)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Anesthesia and Neurotoxicity Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Keywords
- anesthesia, Alzheimer's disease
- MeSH terms
- Alzheimer Disease, Anesthesia, Animals, Hippocampus, Memory, Memory Disorders, Mice, Memory, Long-Term
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