Anaesthesia-induced Changes in Genomic Expression Leading to Neurodegeneration

Khalid Saad Alharbi, Waleed Hassan Almalki, Sami I. Alzarea, Imran Kazmi, Fahad A. Al-Abbasi, Obaid Afzal, Abdulmalik Saleh Altamimi, Mohammed Albratty, Asim Najmi, Gaurav Gupta

Research output: Contribution to journalShort surveypeer-review

16 Scopus citations

Abstract

General anaesthetics (GA) have been in continuous clinical use for more than 170 years, with millions of young and elderly populations exposed to GA to relieve perioperative discomfort and carry out invasive examinations. Preclinical studies have shown that neonatal rodents with acute and chronic exposure to GA suffer from memory and learning deficits, likely due to an imbalance between excitatory and inhibitory neurotransmitters, which has been linked to neurodevelopmental disorders. However, the mechanisms behind anaesthesia-induced alterations in late postnatal mice have yet to be established. In this narrative review, we present the current state of knowledge on early life anaesthesia exposure-mediated alterations of genetic expression, focusing on insights gathered on propofol, ketamine, and isoflurane, as well as the relationship between network effects and subsequent biochem-ical changes that lead to long-term neurocognitive abnormalities. Our review provides strong evidence and a clear picture of anaesthetic agents' pathological events and associated transcriptional changes, which will provide new insights for researchers to elucidate the core ideas and gain an in-depth understanding of molecular and genetic mechanisms. These findings are also helpful in generating more evidence for understanding the exacerbated neuropathology, impaired cognition, and LTP due to acute and chronic exposure to anaesthetics, which will be beneficial for the prevention and treatment of many diseases, such as Alzheimer's disease. Given the many procedures in medical practice that re-quire continuous or multiple exposures to anaesthetics, our review will provide great insight into the possible adverse impact of these substances on the human brain and cognition.

Original languageEnglish
Pages (from-to)411-419
Number of pages9
JournalCNS and Neurological Disorders - Drug Targets
Volume23
Issue number4
DOIs
StatePublished - 2024

Keywords

  • Aβ plaque-associated Alzheimer's disease
  • General anaesthetics
  • depression
  • long-term potentiation
  • neurodegenerative disorders
  • γ-aminobutyric acid A (GABAA) receptor agonist

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