Document Detail

Early exposure to general anesthesia disturbs mitochondrial fission and fusion in the developing rat brain.
MedLine Citation:
PMID:  23411726     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: General anesthetics induce apoptotic neurodegeneration in the developing mammalian brain. General anesthesia (GA) also causes significant disturbances in mitochondrial morphogenesis during intense synaptogenesis. Mitochondria are dynamic organelles that undergo remodeling via fusion and fission. The fine balance between these two opposing processes determines mitochondrial morphometric properties, allowing for their regeneration and enabling normal functioning. As mitochondria are exquisitely sensitive to anesthesia-induced damage, we examined how GA affects mitochondrial fusion/fission.
METHODS: Seven-day-old rat pups received anesthesia containing a sedative dose of midazolam followed by a combined nitrous oxide and isoflurane anesthesia for 6 h.
RESULTS: GA causes 30% upregulation of reactive oxygen species (n = 3-5 pups/group), accompanied by a 2-fold downregulation of an important scavenging enzyme, superoxide dismutase (n = 6 pups/group). Reactive oxygen species upregulation is associated with impaired mitochondrial fission/fusion balance, leading to excessive mitochondrial fission. The imbalance between fission and fusion is due to acute sequestration of the main fission protein, dynamin-related protein 1, from the cytoplasm to mitochondria, and its oligomerization on the outer mitochondrial membrane. These are necessary steps in the formation of the ring-like structures that are required for mitochondrial fission. The fission is further promoted by GA-induced 40% downregulation of cytosolic mitofusin-2, a protein necessary for maintaining the opposing process, mitochondrial fusion (n = 6 pups/group).
CONCLUSIONS: Early exposure to GA causes acute reactive oxygen species upregulation and disturbs the fine balance between mitochondrial fission and fusion, leading to excessive fission and disturbed mitochondrial morphogenesis. These effects may play a causal role in GA-induced developmental neuroapoptosis.
Annalisa Boscolo; Desanka Milanovic; John A Starr; Victoria Sanchez; Azra Oklopcic; Laurie Moy; Carlo Ori C; Alev Erisir; Vesna Jevtovic-Todorovic
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Anesthesiology     Volume:  118     ISSN:  1528-1175     ISO Abbreviation:  Anesthesiology     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-04-24     Completed Date:  2013-06-18     Revised Date:  2014-01-09    
Medline Journal Info:
Nlm Unique ID:  1300217     Medline TA:  Anesthesiology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1086-97     Citation Subset:  AIM; IM    
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MeSH Terms
Anesthesia, General / adverse effects*
Blotting, Western
Brain / drug effects*,  growth & development*,  pathology
Catalase / metabolism
Cytoplasm / metabolism
Down-Regulation / physiology
Dynamins / biosynthesis,  genetics
Homeostasis / physiology
Membrane Proteins / biosynthesis,  genetics
Mitochondrial Dynamics / drug effects*
Mitochondrial Proteins / biosynthesis,  genetics
Rats, Sprague-Dawley
Reactive Oxygen Species / metabolism
Subcellular Fractions / metabolism
Superoxide Dismutase / metabolism
Grant Support
Reg. No./Substance:
0/Membrane Proteins; 0/Mitochondrial Proteins; 0/Reactive Oxygen Species; 0/mitofusin 2 protein, rat; EC; EC Dismutase; EC protein, rat; EC

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