Neonatal Sevoflurane Exposure Induces Adulthood Fear-induced Learning Disability and Decreases Glutamatergic Neurons in the Basolateral Amygdala.
BACKGROUND
Neonatal mice exposed to sevoflurane show certain cognitive and behavioral impairments in adulthood. However, the mechanisms underlying long-term cognitive deficits induced by sevoflurane exposure remain unknown. The present study was performed to investigate whether there is differential neuronal activation between naive mice and sevoflurane-exposed neonates in fear-conditioning tests based on immediate early gene (c-Fos) expression.


METHODS
Male mice were exposed to 3% sevoflurane (SEVO group) or carrier gas alone (no anesthesia, NA group) for 6 hours on postnatal day 6. The mice were allowed to mature before performing the contextual fear-conditioning test. A reduced freezing response was confirmed in the SEVO group. Neural activation in the regions of the medial prefrontal cortex, hippocampus, and amygdala was investigated using c-Fos immunostaining 2 hours after the test. The types of neurons activated were also identified.


RESULTS
The number of c-Fos-positive cells decreased by 27% in the basolateral amygdala in the SEVO group, while no significant changes were observed in other regions. Furthermore, glutamatergic, but not γ-aminobutyric acid (GABA)ergic, neurons expressed c-Fos after the contextual fear-conditioning test in both groups. The number of glutamatergic neurons in the basolateral amygdala in the SEVO group was reduced by 27%.


CONCLUSIONS
Decreased neural activation in the basolateral amygdala may be associated with reduced freezing time in neonatal sevoflurane-exposed mice. Fewer glutamatergic neurons responding to fear stimuli in the basolateral amygdala may contribute to decreased neural activation and learning deficits in mice exposed to sevoflurane as neonates.
Department of Anesthesiology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Maiko
M
Satomoto
Zhongliang
Z
Sun
Yushi U
YU
Adachi
Koshi
K
Makita
D018685:Anesthetics, Inhalation / Q000009:adverse effects*; D000818:Animals; D000831:Animals, Newborn; D066272:Basolateral Nuclear Complex / Q000473:pathology*; D001784:Blood Gas Analysis; D002452:Cell Count; D003213:Conditioning, Psychological; D005239:Fear / Q000523:psychology*; D016762:Genes, fos / Q000187:drug effects; D005971:Glutamates; D007859:Learning Disabilities / Q000139:chemically induced* / Q000473:pathology / Q000523:psychology*; D008297:Male; D008738:Methyl Ethers / Q000009:adverse effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000473:pathology*; D000077149:Sevoflurane; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018685:Anesthetics, Inhalation; D005971:Glutamates; D008738:Methyl Ethers; D000077149:Sevoflurane; D005680:gamma-Aminobutyric Acid