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Increasing the interval between repeated anesthetic exposures reduces long‐lasting synaptic changes in late post‐natal mice
Author(s) -
Ju Xianshu,
Cui Jianchen,
Lee Yulim,
Park Sangil,
Hong Boohwi,
Yoo Sungho,
Kim Yoon Hee,
Ko Youngkwon,
Lim Chaeseong,
Lee Sun Yeul,
Kweon Gi Ryang,
Heo Jun Young,
Chung Woosuk
Publication year - 2021
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.15121
Subject(s) - sevoflurane , anesthetic , hypoactivity , anesthesia , neurotransmission , medicine , synaptic plasticity , inhibitory postsynaptic potential , physiology , endocrinology , receptor
While recent studies strongly suggest that a single, short anesthetic exposure does not affect neurodevelopment, the effects of multiple exposures remain unclear. Unfortunately, studying “multiple exposures” is challenging as it is an extremely heterogeneous descriptor comprising diverse factors. One potentially important, but unrecognized factor is the interval between anesthetic exposures. In order to evaluate the significance of interval, we exposed post‐natal day 16, 17 mice to three sevoflurane exposures (2.5%, 1 hr) with short (2 hr) or long (24 hr) intervals. Changes in synaptic transmission, plasticity, protein expression, and behavior were assessed in male and female mice. We discovered that short‐interval exposures induced a female‐dependent decrease in miniature inhibitory post‐synaptic current (mIPSC) frequency 5 days after the last exposure (control: 18.44 ± 2.86 Hz, sevoflurane:14.65 ± 4.54 Hz). Short‐interval sevoflurane exposed mice also displayed long‐term behavioral deficits at adult age (hypoactivity, anxiety). These behavioral changes were consistent with the sex‐dependent changes in inhibitory transmission, as they were more robust in female mice. Although there was no change in learning and memory, short‐interval sevoflurane exposures also impaired LTP in a non‐sex‐dependent manner (control: 171.10 ± 26.90%, sevoflurane: 149.80 ± 26.48 %). Most importantly, we were unable to find long‐lasting consequences in mice that received long‐interval sevoflurane exposures. Our study provides novel insights regarding the significance of the interval between multiple exposures, and also suggests that the neurotoxic effects of multiple anesthetic exposures may be reduced by simply increasing the interval between each exposure.