TY - JOUR
T1 - GABAergic neurons are susceptible to BAX-dependent apoptosis following isoflurane exposure in the neonatal period
AU - Slupe, Andrew M.
AU - Villasana, Laura
AU - Wright, Kevin M.
N1 - Funding Information:
This work was supported by Foundation for Anesthesia Education and Research (FAER) Research Fellowship Grant (RFG-02-15-17) to AMS and National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS) Grant (R01 NS091027) to KMW. https://www.asahq.org/faer https://www.ninds.nih. gov/ The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors thank Kylee Rosette, B.S., for technical assistance with mouse colony maintenance and anesthesia assays and Mike Jacobson, B.S., for technical assistance with behavioral assays.
Publisher Copyright:
© 2021 Slupe et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2021/1
Y1 - 2021/1
N2 - Exposure to volatile anesthetics during the neonatal period results in acute neuron death. Prior work suggests that apoptosis is the dominant mechanism mediating neuron death. We show that Bax deficiency blocks neuronal death following exposure to isoflurane during the neonatal period. Blocking Bax-mediated neuron death attenuated the neuroinflammatory response of microglia following isoflurane exposure. We find that GABAergic interneurons are disproportionately overrepresented among dying neurons. Despite the increase in neuronal apoptosis induced by isoflurane exposure during the neonatal period, seizure susceptibility, spatial memory retention, and contextual fear memory were unaffected later in life. However, Bax deficiency alone led to mild deficiencies in spatial memory and contextual fear memory, suggesting that normal developmental apoptotic death is important for cognitive function. Collectively, these findings show that while GABAergic neurons in the neonatal brain undergo elevated Bax-dependent apoptotic cell death following exposure to isoflurane, this does not appear to have long-lasting consequences on overall neurological function later in life.
AB - Exposure to volatile anesthetics during the neonatal period results in acute neuron death. Prior work suggests that apoptosis is the dominant mechanism mediating neuron death. We show that Bax deficiency blocks neuronal death following exposure to isoflurane during the neonatal period. Blocking Bax-mediated neuron death attenuated the neuroinflammatory response of microglia following isoflurane exposure. We find that GABAergic interneurons are disproportionately overrepresented among dying neurons. Despite the increase in neuronal apoptosis induced by isoflurane exposure during the neonatal period, seizure susceptibility, spatial memory retention, and contextual fear memory were unaffected later in life. However, Bax deficiency alone led to mild deficiencies in spatial memory and contextual fear memory, suggesting that normal developmental apoptotic death is important for cognitive function. Collectively, these findings show that while GABAergic neurons in the neonatal brain undergo elevated Bax-dependent apoptotic cell death following exposure to isoflurane, this does not appear to have long-lasting consequences on overall neurological function later in life.
UR - http://www.scopus.com/inward/record.url?scp=85099901954&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85099901954&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0238799
DO - 10.1371/journal.pone.0238799
M3 - Article
C2 - 33434191
AN - SCOPUS:85099901954
VL - 16
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 1 January
M1 - e0238799
ER -