TY - JOUR
T1 - Neonatal exposures to sevoflurane in rhesus monkeys alter synaptic ultrastructure in later life
AU - Fehr, Tristan
AU - Janssen, William G.M.
AU - Park, Janis
AU - Baxter, Mark G.
N1 - Funding Information:
We thank Dr. Deanna Benson and Dr. George Huntley for their helpful suggestions on experimental design and for comments on the manuscript. We thank Allison Sowa for her help with electron microscopy protocols, and Camille Casiño for reviewing the manuscript. This research was supported by a 2016 NSF Graduate Research Fellowship (TF), and NICHD grants R01-HD068388 and R01-HD099231 (MGB). Conceptualization: T.F. W.G.M.J. and M.G.B.; Methodology: T.F. W.G.M.J. and M.G.B.; Investigation: T.F. W.G.M.J. and J.P.; Formal analysis: T.F. and M.G.B.; Writing – original draft: T.F.; Writing – review and editing: T.F. and M.G.B.; Funding acquisition: T.F. and M.G.B. The authors declare no competing interests. One or more of the authors of this paper self-identifies as a member of the LGBTQIA+ community. One or more of the authors of this paper self-identifies as a gender minority in their field of research.
Funding Information:
We thank Dr. Deanna Benson and Dr. George Huntley for their helpful suggestions on experimental design and for comments on the manuscript. We thank Allison Sowa for her help with electron microscopy protocols, and Camille Casiño for reviewing the manuscript. This research was supported by a 2016 NSF Graduate Research Fellowship (TF), and NICHD grants R01-HD068388 and R01-HD099231 (MGB).
Publisher Copyright:
© 2022 The Author(s)
PY - 2022/12/22
Y1 - 2022/12/22
N2 - Repeated or prolonged early life exposure to anesthesia is neurotoxic in animals and associated with neurocognitive impairment in later life in humans. We used electron microscopy with unbiased stereological sampling to assess synaptic ultrastructure in dorsolateral prefrontal cortex (dlPFC) and hippocampal CA1 of female and male rhesus monkeys, four years after three 4-h exposures to sevoflurane during the first five postnatal weeks. This allowed us to ascertain long-term consequences of anesthesia exposure without confounding effects of surgery or illness. Synapse areas were reduced in the largest synapses in CA1 and dlPFC, predominantly in perforated spinous synapses in CA1 and nonperforated spinous synapses in dlPFC. Mitochondrial morphology and localization changed subtly in both areas. Synapse areas in CA1 correlated with response to a mild social stressor. Thus, exposure to anesthesia in infancy can cause long-term ultrastructural changes in primates, which may be substrates for long-term alterations in synaptic transmission and behavioral deficits.
AB - Repeated or prolonged early life exposure to anesthesia is neurotoxic in animals and associated with neurocognitive impairment in later life in humans. We used electron microscopy with unbiased stereological sampling to assess synaptic ultrastructure in dorsolateral prefrontal cortex (dlPFC) and hippocampal CA1 of female and male rhesus monkeys, four years after three 4-h exposures to sevoflurane during the first five postnatal weeks. This allowed us to ascertain long-term consequences of anesthesia exposure without confounding effects of surgery or illness. Synapse areas were reduced in the largest synapses in CA1 and dlPFC, predominantly in perforated spinous synapses in CA1 and nonperforated spinous synapses in dlPFC. Mitochondrial morphology and localization changed subtly in both areas. Synapse areas in CA1 correlated with response to a mild social stressor. Thus, exposure to anesthesia in infancy can cause long-term ultrastructural changes in primates, which may be substrates for long-term alterations in synaptic transmission and behavioral deficits.
KW - Cellular neuroscience
KW - Developmental neuroscience
UR - http://www.scopus.com/inward/record.url?scp=85144072647&partnerID=8YFLogxK
U2 - 10.1016/j.isci.2022.105685
DO - 10.1016/j.isci.2022.105685
M3 - Article
AN - SCOPUS:85144072647
SN - 2589-0042
VL - 25
JO - iScience
JF - iScience
IS - 12
M1 - 105685
ER -