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Updated: Aug 5, 2026
In Vivo Chronic Two-Photon Imaging of Microglia in the Mouse Hippocampus
Published on: July 6, 2022
Microglial Activation Is Associated with Hippocampal Synaptic Degeneration and Cognitive Deficits Following Repeated
Liyun Deng1,2, Mengchan Su2,3, Ying Cui1,2
1Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu 610041, China.
Abstract:
Propofol is a widely used intravenous anesthetic with recognized abuse potential; however, the effects of repeated propofol exposure on hippocampal function and cognition remain poorly understood. In the present study, we established a rat model of repeated subanesthetic intraperitoneal propofol administration and demonstrated that propofol induced robust conditioned place preference, indicating rewarding properties. Propofol-exposed rats exhibited significant impairments in hippocampus-dependent cognitive tasks. Transcriptomic analysis revealed marked transcriptional alterations enriched in pathways related to synaptic organization and plasticity following repeated propofol exposure. Consistently, Western blotting, transmission electron microscopy, and Golgi staining demonstrated pronounced reductions in dendritic spine density and synaptic integrity within the hippocampus. Moreover, aberrant microglial activation was observed in the hippocampus and was closely associated with synaptic degeneration and cognitive deficits. Importantly, pharmacological inhibition of microglial activation with minocycline effectively ameliorated propofol-induced cognitive impairment and synaptic degeneration. Collectively, these findings suggest that microglial activation is associated with hippocampal synaptic degeneration and cognitive deficits following repeated propofol exposure and may contribute to these pathological changes.
Insights
Repeated propofol (anesthetic) exposure impairs hippocampus-dependent cognition in rats by causing synaptic damage. Inhibiting microglial activation reversed these cognitive deficits, highlighting microglia's role in propofol's neurotoxicity.
Area of Science:
- Neuroscience
- Pharmacology
- Toxicology
Background:
- Propofol is a common anesthetic with abuse potential.
- Its long-term effects on the hippocampus and cognition are not well understood.
Purpose of the Study:
- To investigate the impact of repeated propofol administration on hippocampal function and cognition.
- To explore the underlying mechanisms, including synaptic changes and microglial activation.
Main Methods:
- A rat model of repeated subanesthetic propofol administration.
- Behavioral testing for hippocampus-dependent cognition.
- Transcriptomic analysis, Western blotting, electron microscopy, and Golgi staining for synaptic integrity.
- Assessment of microglial activation and the effect of minocycline.
Main Results:
- Propofol induced rewarding effects and impaired cognitive function.
- Significant reductions in dendritic spine density and synaptic integrity were observed.
- Aberrant microglial activation in the hippocampus correlated with cognitive deficits.
- Minocycline treatment ameliorated propofol-induced cognitive impairments and synaptic damage.
Conclusions:
- Repeated propofol exposure leads to hippocampal synaptic degeneration and cognitive deficits.
- Microglial activation is implicated in these pathological changes.
- Inhibiting microglial activation may be a therapeutic strategy against propofol-induced neurotoxicity.
