TY - JOUR
T1 - General anesthesia alters CNS and astrocyte expression of activity-dependent and activity-independent genes
AU - Jiwaji, Zoeb
AU - Márkus, Nóra M
AU - McQueen, Jamie
AU - Emelianova, Katie
AU - He, Xin
AU - Dando, Owen
AU - Chandran, Siddharthan
AU - Hardingham, Giles E
N1 - Copyright © 2023 Jiwaji, Márkus, McQueen, Emelianova, He, Dando, Chandran and Hardingham.
PY - 2023/8/21
Y1 - 2023/8/21
N2 - General anesthesia represents a common clinical intervention and yet can result in long-term adverse CNS effects particularly in the elderly or dementia patients. Suppression of cortical activity is a key feature of the anesthetic-induced unconscious state, with activity being a well-described regulator of pathways important for brain health. However, the extent to which the effects of anesthesia go beyond simple suppression of neuronal activity is incompletely understood. We found that general anesthesia lowered cortical expression of genes induced by physiological activity
in vivo, and recapitulated additional patterns of gene regulation induced by total blockade of firing activity
in vitro, including repression of neuroprotective genes and induction of pro-apoptotic genes. However, the influence of anesthesia extended beyond that which could be accounted for by activity modulation, including the induction of non activity-regulated genes associated with inflammation and cell death. We next focused on astrocytes, important integrators of both neuronal activity and inflammatory signaling. General anesthesia triggered gene expression changes consistent with astrocytes being in a low-activity environment, but additionally caused induction of a reactive profile, with transcriptional changes enriched in those triggered by stroke, neuroinflammation, and Aß/tau pathology. Thus, while the effects of general anesthesia on cortical gene expression are consistent with the strong repression of brain activity, further deleterious effects are apparent including a reactive astrocyte profile.
AB - General anesthesia represents a common clinical intervention and yet can result in long-term adverse CNS effects particularly in the elderly or dementia patients. Suppression of cortical activity is a key feature of the anesthetic-induced unconscious state, with activity being a well-described regulator of pathways important for brain health. However, the extent to which the effects of anesthesia go beyond simple suppression of neuronal activity is incompletely understood. We found that general anesthesia lowered cortical expression of genes induced by physiological activity
in vivo, and recapitulated additional patterns of gene regulation induced by total blockade of firing activity
in vitro, including repression of neuroprotective genes and induction of pro-apoptotic genes. However, the influence of anesthesia extended beyond that which could be accounted for by activity modulation, including the induction of non activity-regulated genes associated with inflammation and cell death. We next focused on astrocytes, important integrators of both neuronal activity and inflammatory signaling. General anesthesia triggered gene expression changes consistent with astrocytes being in a low-activity environment, but additionally caused induction of a reactive profile, with transcriptional changes enriched in those triggered by stroke, neuroinflammation, and Aß/tau pathology. Thus, while the effects of general anesthesia on cortical gene expression are consistent with the strong repression of brain activity, further deleterious effects are apparent including a reactive astrocyte profile.
U2 - 10.3389/fnetp.2023.1216366
DO - 10.3389/fnetp.2023.1216366
M3 - Article
C2 - 37670849
SN - 2674-0109
VL - 3
SP - 1216366
JO - Frontiers in network physiology
JF - Frontiers in network physiology
ER -