Anesthesia induces neuronal cell death in the developing rat brain via the intrinsic and extrinsic apoptotic pathways

Content Provider	Semantic Scholar
Author	Yon, Jung-Min Daniel-Johnson, Jennifer Carter, Lisa B. Jevtovic-Todorovic, Vesna
Copyright Year	2005
Abstract	It was shown recently that exposure of the developing rat brain during the peak of synaptogenesis to commonly used general anesthetics can trigger widespread apoptotic neurodegeneration in many regions of the developing rat brain and persistent learning/memory deficits later on in life. To understand the mechanism by which general anesthetics induce apoptotic neuronal death we studied two common apoptotic pathways-the intrinsic and the extrinsic pathway-at different time points during synaptogenesis. We found that the intrinsic pathway is activated early on during anesthesia exposure (within two hours), as measured by the down-regulation of bcl-x(L), up-regulation of cytochrome c and the activation of caspase-9 in 7-day-old rats (the peak of synaptogenesis), but remains inactivated in 14-day-old rats (the end of synaptogenesis). The extrinsic pathway is activated later on (within six hours of anesthesia exposure), as measured by the up-regulation of Fas protein and the activation of caspase-8 in 7-day-old rats, but remains inactivated in 14-day-old rats. Anesthesia-induced apoptotic neurodegeneration is age dependent with vulnerability closely correlating with the timing of synaptogenesis, i.e. the developing brain is most sensitive at the peak of synaptogenesis (7 days old) and least sensitive at the end of synaptogenesis (14 days old).
Starting Page	815
Ending Page	827
Page Count	13
File Format	PDF HTM / HTML
DOI	10.1016/j.neuroscience.2005.03.064
PubMed reference number	16154281
Journal	Medline
Volume Number	135
Alternate Webpage(s)	https://api.elsevier.com/content/article/pii/S0306452205003088
Alternate Webpage(s)	https://www.sciencedirect.com/science/article/pii/S0306452205003088?dgcid=api_sd_search-api-endpoint
Alternate Webpage(s)	https://doi.org/10.1016/j.neuroscience.2005.03.064
Journal	Neuroscience
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article