Heatstroke-induced late-onset neurological deficits in mice caused by white matter demyelination, Purkinje cell degeneration, and synaptic impairment in the cerebellum.

Heatstroke-induced late-onset neurological deficits in mice caused by white matter demyelination, Purkinje cell degeneration, and synaptic impairment in the cerebellum.
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DOI:
10.1038/s41598-022-14849-9
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发表时间:
2022-06-22
期刊:
影响因子:
4.6
通讯作者:
Dohi, Kenji
Dohi, Kenji
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Miyamoto, Kazuyuki;Nakamura, Motoyasu;Ohtaki, Hirokazu;Suzuki, Keisuke;Yamaga, Hiroki;Yanagisawa, Kaoru;Maeda, Atsuo;Yagi, Masaharu;Hayashi, Munetaka;Honda, Kazuho;Dohi, Kenji

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全球变暖增加了中暑的发生率。中暑后,患者会出现神经症状,表明小脑受损。然而,人们对潜在的长期不良后果知之甚少。我们用小鼠中暑模型研究了中暑后小脑的变化。在本研究中,运动协调障碍在中暑后3周明显出现,并在一定程度上逐渐改善。中暑后1周和3周,小脑可见白质脱髓鞘,而胼胝体未见白质脱髓鞘。中暑后1周、3周和9周,浦肯野细胞数量显著减少。突触素和突触后密度-95的强度在中暑后3周暂时减弱,但两者在中暑后9周似乎都增强。运动协调性丧失在中暑后几周内出现,并有一定程度的恢复。通过小脑白质髓鞘染色和突触前、后标记的浦肯野细胞的免疫组织化学染色,推测迟发性运动障碍是由小脑功能障碍引起的。浦肯野细胞数量在9周后没有恢复;其他因素,包括运动协调,部分恢复,可能是通过突触重建、残留的浦肯野细胞和其他小脑白质重新髓鞘形成。这些现象与中暑后迟发性神经功能障碍和恢复有关。
Global warming increases heatstroke incidence. After heatstroke, patients exhibit neurological symptoms, suggesting cerebellar damage. However, the potential long-term adverse outcomes are poorly understood. We studied the cerebellum after heatstroke in mouse heatstroke models. In this study, motor coordination disorder significantly appeared 3 weeks after heatstroke and gradually improved to some extent. Although white matter demyelination was detected at 1 and 3 weeks after heatstroke in the cerebellum, it was not found in the corpus callosum. The Purkinje cell numbers significantly decreased at 1, 3, and 9 weeks after heatstroke. The intensity of synaptophysin and postsynaptic density-95 temporarily appeared to attenuate at 3 weeks after heatstroke; however, both appeared to intensify at 9 weeks after heatstroke. Motor coordination loss occurred a few weeks after heatstroke and recovered to some extent. Late-onset motor impairment was suggested to be caused by cerebellar dysfunctions morphologically assessed by myelin staining of cerebellar white matter and immunostaining of Purkinje cells with pre- and postsynaptic markers. Purkinje cell number did not recover for 9 weeks; other factors, including motor coordination, partially recovered, probably by synaptic reconstruction, residual Purkinje cells, and other cerebellar white matter remyelination. These phenomena were associated with late-onset neurological deficits and recovery after heatstroke.
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