TY - JOUR
T1 - Anaesthesia-induced Changes in Genomic Expression Leading to Neurodegeneration
AU - Alharbi, Khalid Saad
AU - Almalki, Waleed Hassan
AU - Alzarea, Sami I.
AU - Kazmi, Imran
AU - Al-Abbasi, Fahad A.
AU - Afzal, Obaid
AU - Saleh Altamimi, Abdulmalik
AU - Albratty, Mohammed
AU - Najmi, Asim
AU - Gupta, Gaurav
N1 - Publisher Copyright:
© 2024 Bentham Science Publishers.
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
KW - Aβ plaque-associated Alzheimer's disease
KW - General anaesthetics
KW - depression
KW - long-term potentiation
KW - neurodegenerative disorders
KW - γ-aminobutyric acid A (GABAA) receptor agonist
UR - http://www.scopus.com/inward/record.url?scp=85184344931&partnerID=8YFLogxK
U2 - 10.2174/1871527322666230508123558
DO - 10.2174/1871527322666230508123558
M3 - Short survey
C2 - 37157197
AN - SCOPUS:85184344931
SN - 1871-5273
VL - 23
SP - 411
EP - 419
JO - CNS and Neurological Disorders - Drug Targets
JF - CNS and Neurological Disorders - Drug Targets
IS - 4
ER -