Neonatal exposures to sevoflurane in rhesus monkeys alter synaptic ultrastructure in later life.

Neonatal exposures to sevoflurane in rhesus monkeys alter synaptic ultrastructure in later life.
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恒河猴新生儿暴露于七氟烷会改变晚年突触超微结构。

DOI:
10.1016/j.isci.2022.105685
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发表时间:
2022-12-22
期刊:
影响因子:
5.8
通讯作者:
Baxter, Mark G.
Baxter, Mark G.
中科院分区:
综合性期刊2区
文献类型:
--
作者:
Fehr, Tristan;Janssen, William G. M.;Park, Janis;Baxter, Mark G.

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反复或长期的早期麻醉暴露对动物具有神经毒性,并与人类晚年的神经认知障碍有关。我们使用电子显微镜无偏体视学采样,以评估突触超微结构的背外侧前额叶皮层(dlPFC)和海马CA 1的雌性和雄性恒河猴,四年后,三个4小时的暴露于七氟烷在出生后的前五周。这使我们能够确定麻醉暴露的长期后果,而不会混淆手术或疾病的影响。突触面积减少的最大的突触在CA 1和dlPFC,主要是在穿孔的棘状突触在CA 1和非穿孔的棘状突触在dlPFC。线粒体的形态和定位在这两个领域的微妙变化。CA 1区的突触区与对轻度社会压力的反应相关。因此,暴露于麻醉在婴儿期可以引起长期的超微结构变化的灵长类动物,这可能是长期的改变突触传递和行为缺陷的基板。新生儿麻醉数年后改变海马和前额皮质突触麻醉的长期影响因突触靶点、复杂性和区域而异CA 1的平均突触面积与改变的社会情绪行为呈负相关一般而言,雄性和雌性猴子受到麻醉的影响相似发育神经科学;细胞神经科学
Repeated or prolonged early life exposure to anesthesia is neurotoxic in animals and associated with neurocognitive impairment in later life in humans. We used electron microscopy with unbiased stereological sampling to assess synaptic ultrastructure in dorsolateral prefrontal cortex (dlPFC) and hippocampal CA1 of female and male rhesus monkeys, four years after three 4-h exposures to sevoflurane during the first five postnatal weeks. This allowed us to ascertain long-term consequences of anesthesia exposure without confounding effects of surgery or illness. Synapse areas were reduced in the largest synapses in CA1 and dlPFC, predominantly in perforated spinous synapses in CA1 and nonperforated spinous synapses in dlPFC. Mitochondrial morphology and localization changed subtly in both areas. Synapse areas in CA1 correlated with response to a mild social stressor. Thus, exposure to anesthesia in infancy can cause long-term ultrastructural changes in primates, which may be substrates for long-term alterations in synaptic transmission and behavioral deficits. Neonatal anesthesia alters hippocampus and prefrontal cortex synapses years later Anesthesia’s long-term impacts vary by synapse target, complexity, and region Mean synapse area in CA1 negatively correlates with altered socioemotional behavior In general, male and female monkeys were affected similarly by anesthesia Developmental neuroscience; Cellular neuroscience
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