Neonatal Exposure to Low-Dose (1.2%) Sevoflurane Increases Rats' Hippocampal Neurogenesis and Synaptic Plasticity in Later Life
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1Department of Anaesthesiology, The First Affiliated Hospital of Sun Yat-Sen University, No. 58 Zhongshan Road 2, Guangzhou, 510080, Guangdong, People's Republic of China.
Insights
Low-dose sevoflurane anesthesia in infant rats enhanced hippocampus-dependent learning and memory. This effect was linked to increased neurogenesis and synaptic plasticity in the developing brain.
Area of Science:
- Neuroscience
- Developmental Biology
- Anesthesiology
Background:
- General anesthetics like sevoflurane are increasingly used in infants and children.
- Concerns exist regarding their long-term effects on cognitive development.
- Previous animal studies suggest potential benefits of low-dose sevoflurane on cognitive function.
Purpose of the Study:
- To investigate the long-term effects of low-dose sevoflurane exposure on hippocampus-dependent learning and memory in developing rats.
- To explore the impact on neurogenesis and synaptic plasticity.
Main Methods:
- Rats were exposed to 1.2% or 2.4% sevoflurane, or air control, on postnatal day 7 for 6 hours.
- Hippocampus-dependent learning and memory were assessed using the Morris water maze.
- Neurogenesis, synaptic plasticity, and related protein expression (BDNF, TrkB, PSD-95, synaptophysin) were analyzed.
Main Results:
- Neonatal exposure to 1.2% sevoflurane improved spatial learning and memory in juvenile rats.
- This low-dose exposure increased neurogenesis (BrdU-positive cells) and enhanced synaptic number and ultrastructure in the hippocampus.
- Higher sevoflurane concentrations (2.4%) did not yield significant cognitive or neuroplasticity improvements compared to controls.
Conclusions:
- Exposure to a low concentration (1.2%) of sevoflurane during a critical developmental window can promote cognitive function and hippocampal plasticity.
- These findings suggest that low-dose sevoflurane may have beneficial effects on spatial learning and memory, warranting further investigation into its neurodevelopmental impact.
Abstract:
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.