The effect of sevoflurane inhalation on gabaergic neurons activation: observation on the GAD67-GFP knock-in mouse.
The mechanisms underlying volatile anesthesia agents are not well elucidated. Emerging researches have focused on the participation of γ-aminobutyric acid (GABA) neurons but there still lacks morphological evidence. To elucidate the possible activation of GABAergic neurons by sevoflurane inhalation in morphology, Fos (as neuronal activity marker) and GABA neurons double labeling were observed on the brain of glutamic acid decarboxylase (GAD) 67-GFP knock-in mice after sevoflurane inhalation. Twenty GAD67-GFP knock-in mice were divided into three groups: S1 group: incomplete anesthesia state induced by sevoflurane; S2 group: complete anesthesia state induced by sevoflurane; control(C) group. Sevoflurane induced a significant increase of Fos expression in the dorsomedial hypothalamic nucleus (DM), periaqueductal grey (PAG), hippocampus (CA1, DG), paraventricular thalamic nucleus (PV), lateral septal nucleus (LS), and cingulate cortex (Cg1 and Cg2) in S1 group compared to C group, and increase of Fos expression in S2 group compared to S1 group. In S2 group, Fos was only expressed in the medial amygdaloid nucleus (MeA), Edinger-Westphal (E-W) nucleus, arcuate hypothalamic nucleus (Arc) and the ventral part of paraventricular hypothalamic nucleus (PaV). Double immunofluroscent staining indicated that in LS, almost all Fos were present in GABAergic neurons. In CA1, DG, DM, cg1, cg2, and PAG, Fos was expressed as well, but only few were present in GABAergic neurons. Fos expression was very high in thalamus, but no coexistence were found as no GABAergic neuron was detected in this area. Our results provided morphological evidence that GABAergic transmission in specific brain areas may participate in the sevoflurane-induced anesthesia.
Department of Anesthesiology, School of Stomatology, Fourth Military Medical University, Xi'an, People's Republic of China.
Li-Chun
LC
Han
Hui
H
Zhang
Wei
W
Wang
Yan-Yan
YY
Wei
Xing-Xing
XX
Sun
Youchio
Y
Yanagawa
Yun-Qing
YQ
Li
Li-Xian
LX
Xu
Sheng-Xi
SX
Wu
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D001931:Brain Mapping / Q000379:methods; D005455:Fluorescent Antibody Technique; D055879:Gene Knock-In Techniques; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006579:Heterozygote; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D000077149:Sevoflurane; D005680:gamma-Aminobutyric Acid / Q000187:drug effects* / Q000378:metabolism
D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D049452:Green Fluorescent Proteins; D000077149:Sevoflurane; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1