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General anesthesia alters CNS and astrocyte expression of activity-dependent and activity-independent genes

Zoeb Jiwaji1,2,3,4, Nóra M Márkus1,2, Jamie McQueen1,2

  • 1UK Dementia Research Institute, Edinburgh Medical School, The University of Edinburgh, Edinburgh, United Kingdom.

Frontiers in Network Physiology
|September 6, 2023
PubMed

Insights

General anesthesia suppresses brain activity and alters gene expression, potentially harming brain health, especially in elderly or dementia patients. This study reveals anesthesia's effects extend beyond activity suppression, inducing inflammation and reactive astrocytes.

Area of Science:

  • Neuroscience
  • Anesthesiology
  • Molecular Biology

Background:

  • General anesthesia is common but can cause long-term central nervous system (CNS) adverse effects, particularly in vulnerable populations like the elderly or dementia patients.
  • Neuronal activity is crucial for brain health, and its suppression is a hallmark of anesthetic-induced unconsciousness.
  • The full impact of anesthesia on brain gene regulation beyond simple activity suppression remains unclear.

Purpose of the Study:

  • To investigate the comprehensive effects of general anesthesia on cortical gene expression.
  • To determine if anesthesia-induced gene expression changes are solely due to suppressed neuronal activity.
  • To examine the specific impact of general anesthesia on astrocyte gene expression profiles.

Main Methods:

  • Analysis of cortical gene expression changes following general anesthesia in vivo.
  • Comparison with gene expression patterns from in vitro studies involving complete blockade of neuronal firing.
  • Focused analysis of astrocyte gene expression changes in response to anesthesia.

Main Results:

  • General anesthesia reduced the expression of activity-dependent genes in the cortex.
  • Anesthesia induced gene expression patterns associated with neuroprotection repression and apoptosis promotion, mirroring complete neuronal inactivity.
  • Anesthesia also triggered non-activity-regulated genes linked to inflammation and cell death.
  • Astrocytes exhibited gene expression changes indicative of both low activity and a reactive state, similar to conditions like stroke and neuroinflammation.

Conclusions:

  • General anesthesia's effects on cortical gene expression align with significant repression of brain activity.
  • Anesthesia induces additional deleterious effects beyond activity suppression, including inflammation and cell death pathways.
  • General anesthesia promotes a reactive astrocyte profile, suggesting a detrimental impact on brain health, particularly in susceptible individuals.
Keywords:
astrocytesgeneral anesthesianeurodegenerating diseasessynaptic activitytranscriptional regulation

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