AUTHOR=Zeng Shuang , Zhu Ruilou , Wang Yangyang , Yang Yitian , Li Ningning , Fu Ningning , Sun Mingyang , Zhang Jiaqiang 

TITLE=Role of GABAA receptor depolarization-mediated VGCC activation in sevoflurane-induced cognitive impairment in neonatal mice

JOURNAL=Frontiers in Cellular Neuroscience

VOLUME=16

YEAR=2022

URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2022.964227

DOI=10.3389/fncel.2022.964227

ISSN=1662-5102

ABSTRACT=<sec><title>Background</title><p>In neonatal mice, anesthesia with sevoflurane depolarizes the GABA Type A receptor (GABA<sub>A</sub>R), which leads to cognitive impairment. Calcium accumulation in neurons can lead to neurotoxicity. Voltage-gated calcium channels (VGCCs) can increase intracellular calcium concentration under isoflurane and hypoxic conditions. The underlying mechanisms remain largely unknown.</p></sec><sec><title>Methods</title><p>Six-day-old mice were anesthetized with 3% sevoflurane for 2 h/day for 3 days. The Y-Maze, new object recognition (NOR) test, the Barnes maze test, immunoassay, immunoblotting, the TUNEL test, and Golgi–Cox staining were used to assess cognition, calcium concentration, inflammatory response, GABA<sub>A</sub>R activation, VGCC expression, apoptosis, and proliferation of hippocampal nerve cells in mice and HT22 cells.</p></sec><sec><title>Results</title><p>Compared with the control group, mice in the sevoflurane group had impaired cognitive function. In the sevoflurane group, the expression of Gabrb3 and Cav1.2 in the hippocampal neurons increased (<italic>p</italic> &lt; 0.01), the concentration of calcium ions increased (<italic>p</italic> &lt; 0.01), inflammatory reaction and apoptosis of neurons increased (<italic>p</italic> &lt; 0.01), the proliferation of neurons in the DG area decreased (<italic>p</italic> &lt; 0.01), and dendritic spine density decreased (<italic>p</italic> &lt; 0.05). However, the inhibition of Gabrb3 and Cav1.2 alleviated cognitive impairment and reduced neurotoxicity.</p></sec><sec><title>Conclusions</title><p>Sevoflurane activates VGCCs by inducing GABA<sub>A</sub>R depolarization, resulting in cognitive impairment. Activated VGCCs cause an increase in intracellular calcium concentration and an inflammatory response, resulting in neurotoxicity and cognitive impairment.</p></sec>