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

中暑引起的小鼠迟发性神经功能障碍是由白质脱髓鞘、浦肯野细胞变性和小脑突触损伤引起的

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作者:Kazuyuki Miyamoto, Motoyasu Nakamura, Hirokazu Ohtaki, Keisuke Suzuki, Hiroki Yamaga, Kaoru Yanagisawa, Atsuo Maeda, Masaharu Yagi, Munetaka Hayashi, Kazuho Honda, Kenji Dohi

Abstract

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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