Prenatal sevoflurane exposure causes abnormal development of the entorhinal cortex in rat offspring

² Department of Anesthesiology, Guangdong Hospital of Traditional Chinese Medicine (The Second Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine), 510120 Guangzhou, Guangdong, China

³ Department of Anesthesiology, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, 201318 Shanghai, China

^*Correspondence: songxingrong@gwcmc.org (Xingrong Song)

J. Integr. Neurosci. 2021, 20(3), 613–622; https://doi.org/10.31083/j.jin2003065

Submitted: 14 March 2021 | Revised: 26 March 2021 | Accepted: 12 May 2021 | Published: 30 September 2021

This is an open access article under the CC BY 4.0 license (https://creativecommons.org/licenses/by/4.0/).

Abstract

As a gamma-aminobutyric acid type A receptor agonist sevoflurane is a common general anesthetic used in anesthesia and affects the neural development in offspring. We hypothesized that sevoflurane could regulate interneurons via the neuregulin-1-epidermal growth factor receptor-4 (NRG1–ErbB4) pathway in the entorhinal cortex (ECT) of the middle pregnancy. Six female rats in middle pregnancy (14.5 days of pregnancy) were randomly and equally divided into sevoflurane (SeV) and control groups. The rats in the SeV group were exposed to 4% sevoflurane for 3 hours. The expression levels of NRG1 and ErbB4, parvalbumin (PV) and glutamic acid decarboxylase (GAD67), and N-methyl-D-aspartate receptor subunit 2A (NR2A) and subunit 2B (NR2B) in offspring were examined through immunohistochemistry. The pyramidal neurons in the ECT were examined via Golgi staining. The levels of NRG1 and ErbB4 were significantly decreased (P $<$ 0.01) and the levels of PV and GAD67 (interneurons) were found to be decreased in the SeV group (P $<$ 0.01). The level of NR2B was found to be increased while the level of NR2A being decreased in the SeV group (P $<$ 0.01). The development of pyramidal neurons was abnormal in the SeV group (P $<$ 0.05). Conclusively, prenatal sevoflurane exposure could lead to the disturbance of the interneurons by activating the NRG1–ErbB4 pathway and subsequently result in abnormal development of pyramidal neurons in middle pregnancy. Prenatal sevoflurane exposure in middle pregnancy could be potentially harmful to the neural development of rat offspring. This study may reveal a novel pathway in the influence mechanism of sevoflurane on rat offspring.

Keywords

Sevoflurane

Interneurons

Middle pregnancy

NRG1–ErbB4

Entorhinal cortex

Figures

Fig. 1.

Previous article in this issue

Next article in this issue

Fig. 1.

Exposure of sevoflurane to maternal rats impaired the NRG1–ErbB4 signaling pathway in the LII/LIII entorhinal cortex of offspring. Inverted fluorescence microscopy showed that the NRG1 and ErbB4 positive cells were stained with green fluorescence. The top picture shows the field of vision under the 100 $\times{}$ light microscope of the inverted fluorescence microscope. We used the inverted fluorescence microscope to scan the whole picture of immunofluorescence staining of 100 $\times{}$ rat brain slices. In the whole picture, the area in the white box is pyramidal neurons in the LII/LIII entorhinal cortex. In the control (A and C) and sevoflurane (B and D) groups, A and B show the NRG1 positive cells in the LII/LIII entorhinal cortex of the P30 progeny. C and D show the ErbB4 positive cells. The numbers were significantly decreased in the sevoflurane group compared to the control group (E and F). Note: The symbol ‘**’ represented there was significant difference between groups under the significant level of 0.01.

1 of 4

J. Integr. Neurosci. Print ISSN 0219-6352 Electronic ISSN 1757-448X