Neonatal Exposure to Low-Dose (1.2%) Sevoflurane Increases Rats’ Hippocampal Neurogenesis and Synaptic Plasticity in Later Life
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The increasing usage of general anesthetics on young children and infants has drawn extensive attention to the effects of these drugs on cognitive function later in life. Recent animal studies have revealed improvement in hippocampus-dependent performance after lower concentrations of sevoflurane exposure. However, the long-term effects of low-dose sevoflurane on the developing brain remain elusive. On postnatal day (P) 7, rats were treated with 1.2% sevoflurane (1.2% sevo group), 2.4% sevoflurane (2.4% sevo group), and air control (C group) for 6 h. On P35–40, rats’ hippocampus-dependent learning and memory was tested using the Morris water maze. Cognition-related and synapse-related proteins in the hippocampus were measured using Western blotting on P35. On the same day, neurogenesis and synapse ultrastructure were evaluated using immunofluorescence and transmission electron microscopy (TEM). On P35, the rats neonatally exposed to 1.2% sevoflurane showed better behavioral results than control rats, but not in the 2.4% sevo group. Exposure to 1.2% sevoflurane increased the number of 5′-bromo-2-deoxyuridine (BrdU)-positive cells in the dentate gyrus and improved both synaptic number and ultrastructure in the hippocampus. The expression levels of BDNF, TrkB, postsynaptic density (PSD)-95, and synaptophysin in the hippocampus were also increased in the 1.2% sevo group. In contrast, no significant changes in neurogenesis or synaptic plasticity were observed between the C group and the 2.4% sevo group on P35. These results showed that exposure of the developing brain to a low concentration of sevoflurane for 6 h could promote spatial learning and memory function, along with increased hippocampal neurogenesis and synaptic plasticity, in later life.
KeywordsSevoflurane Hippocampus Cognitive function Neurogenesis Synaptic plasticity
This work was supported by the grants from the National Natural Science Foundation of China (No. 81571032 to Xia Feng and No. 81701047 to Xue Zhou).
Compliance with Ethical Standards
The use of rats in this study was approved by the Institutional Animal Care and Use Committee at Sun Yat-sen University (Guangzhou, China). All experiments were in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals and ARRIVE guidelines.
Conflict of Interest
The authors declare that they have no conflict of interest.
- Chen C, Shen FY, Zhao X, Zhou T, Xu DJ, Wang ZR, Wang YW (2015) Low-dose sevoflurane promotes hippocampal neurogenesis and facilitates the development of dentate gyrus-dependent learning in neonatal rats. ASN neuro 7(2):175909141557584. https://doi.org/10.1177/1759091415575845 CrossRefGoogle Scholar
- Feng X, Liu JJ, Zhou X, Song FH, Yang XY, Chen XS, Huang WQ, Zhou LH, Ye JH (2012) Single sevoflurane exposure decreases neuronal nitric oxide synthase levels in the hippocampus of developing rats. Br J Anaesth 109(2):225–233. https://doi.org/10.1093/bja/aes121 CrossRefPubMedPubMedCentralGoogle Scholar
- Gray JD, Milner TA, McEwen BS (2013) Dynamic plasticity: the role of glucocorticoids, brain-derived neurotrophic factor and other trophic factors. Neuroscience 239:214–227. https://doi.org/10.1016/j.neuroscience.2012.08.034 CrossRefPubMedGoogle Scholar
- Head E, Corrada MM, Kahle-Wrobleski K, Kim RC, Sarsoza F, Goodus M, Kawas CH (2009) Synaptic proteins, neuropathology and cognitive status in the oldest-old. Neurobiol Aging 30(7):1125–1134. https://doi.org/10.1016/j.neurobiolaging.2007.10.001 CrossRefPubMedGoogle Scholar
- Jevtovic-Todorovic V, Hartman RE, Izumi Y, Benshoff ND, Dikranian K, Zorumski CF, Olney JW, Wozniak DF (2003) Early exposure to common anesthetic agents causes widespread neurodegeneration in the developing rat brain and persistent learning deficits. J Neurosci : Off J Soc Neurosci 23(3):876–882CrossRefGoogle Scholar
- Liang G, Ward C, Peng J, Zhao Y, Huang B, Wei H (2010) Isoflurane causes greater neurodegeneration than an equivalent exposure of sevoflurane in the developing brain of neonatal mice. Anesthesiology 112(6):1325–1334. https://doi.org/10.1097/ALN.0b013e3181d94da5 CrossRefPubMedPubMedCentralGoogle Scholar
- Mellon RD, Simone AF, Rappaport BA (2007) Use of anesthetic agents in neonates and young children. Anesth Analg 104(3):509–520. https://doi.org/10.1213/01.ane.0000255729.96438.b0 CrossRefPubMedGoogle Scholar
- Payne RS, Akca O, Roewer N, Schurr A, Kehl F (2005) Sevoflurane-induced preconditioning protects against cerebral ischemic neuronal damage in rats. Brain ResGoogle Scholar
- Sairanen M, Lucas G, Ernfors P, Castren M, Castren E (2005) Brain-derived neurotrophic factor and antidepressant drugs have different but coordinated effects on neuronal turnover, proliferation, and survival in the adult dentate gyrus. J Neurosci : Off J Soc Neurosci 25:1089–1094CrossRefGoogle Scholar