Effects of clesmatine on myelination and neuronal activity during sleep in the hippocampus of adult APP/PS1 mice

YANG Ye; ZHANG Haibo; LIU Yanji; YAO Zhongxiang; HU Bo

doi:10.16016/j.2097-0927.202505023

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Effects of clesmatine on myelination and neuronal activity during sleep in the hippocampus of adult APP/PS1 mice

Monographic Reports | 更新时间：2025-08-25

- Effects of clesmatine on myelination and neuronal activity during sleep in the hippocampus of adult APP/PS1 mice
- Journal of Army Medical University Vol. 47, Issue 16, Pages: 1838-1848(2025)
- 作者机构：
  
  1.陆军军医大学（第三军医大学）基础医学院：，基础医学教学实验中心，重庆
  2.陆军军医大学（第三军医大学）基础医学院：，生理学教研室，重庆
- 作者简介：
  
  YAO Zhongxaing， E-mail： yaozhx@yahoo.com
  HU Bo， E-mail： bohu@tmmu.edu.cn；
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(32071014);the Joint Innovation and Development Fund of Natural Science Foundation of Chongqing(CSTB2023NSCQ-LZX0153)
- DOI：10.16016/j.2097-0927.202505023
  CLC： R322.81;R745.7;R976
- Received：12 May 2025，
  
  Revised：21 May 2025，
  
  Published：30 August 2025
- 稿件说明：
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杨叶,张海波,刘彦吉,等.氯马斯汀对APP/PS1小鼠成年期海马髓鞘化和睡眠期神经活动的影响[J].陆军军医大学学报,2025,47(16):1838-1848.

YANG Ye,ZHANG Haibo,LIU Yanji,et al.Effects of clesmatine on myelination and neuronal activity during sleep in the hippocampus of adult APP/PS1 mice[J].J Army Med Univ,2025,47(16):1838-1848.
杨叶,张海波,刘彦吉,等.氯马斯汀对APP/PS1小鼠成年期海马髓鞘化和睡眠期神经活动的影响[J].陆军军医大学学报,2025,47(16):1838-1848. DOI：10.16016/j.2097-0927.202505023.

YANG Ye,ZHANG Haibo,LIU Yanji,et al.Effects of clesmatine on myelination and neuronal activity during sleep in the hippocampus of adult APP/PS1 mice[J].J Army Med Univ,2025,47(16):1838-1848. DOI：10.16016/j.2097-0927.202505023.

摘要

目的

研究氯马斯汀处理对APP/PS1小鼠成年期海马髓鞘化和睡眠期间神经振荡及相关神经元放电活动的影响。

方法

连续饮水口服氯马斯汀3个月，促进成年期APP/PS1小鼠大脑髓鞘化。根据给药情况，将小鼠分为3组：APP/PS1组、APP/PS1+Clemastine组、野生型（WT）组。结合海马局部场电位和头部三维加速度信号特征判定小鼠的睡眠和觉醒状态（觉醒、NREM睡眠、REM睡眠）。在体多通道记录连续监测背侧海马神经元在觉醒、NREM睡眠和REM睡眠状态下的放电活动。

结果

①饮水口服氯马斯汀可以使APP/PS1+Clemastine组小鼠MBP

蛋白表达水平显著高于APP/PS1组（

0.001）。②氯马斯汀处理不会改变APP/PS1小鼠日间时相中NREM睡眠、REM睡眠和觉醒所占的时间比例（

0.05）。③ 氯马斯汀处理降低APP/PS1小鼠海马锥体细胞的平均放电频率（

0.05）、增加该区中间神经元的平均放电频率（

0.05）。④ 氯马斯汀处理增加NREM睡眠期海马SWR振荡发生率，并特异性降低APP/PS1小鼠海马锥体细胞在SWR（Sharp wave ripple）振荡发生时的放电频率（

0.05）。⑤氯马斯汀处理对APP/PS1小鼠海马神经元在REM睡眠期theta振荡发生时的放电活动无显著影响（

0.05）。

结论

氯马斯汀可促进APP/PS1小鼠成年期海马髓鞘化，改善NREM睡眠期SWR振荡发生及其相关的海马神经元放电活动。

Abstract

Objective‍　‍To investigate the effects of clesmatine on the myelination and neural oscillation-related firing activities during sleep in the hippocampus of adult APP/PS1 mice. Methods‍　‍Oral administration of clemastine in drinking water was given to APP/PS1 mice for 3 months to enhance myelination in adulthood. Based on the treatment regimens

the mice were randomly assigned into APP/PS1 group

APP/PS1+clemastine group

and wild-type (WT) group. Local field potentials combined with three-dimensional acceleration of the head and neck were employed to determine the brain states

that is

wakefulness

non-rapid eye movement (NREM) sleep

REM sleep.

In vivo

multi-electrode arrays were utilized to continuously monitor neuronal firing activities in the dorsal hippocampus across the 3 sleep states. Results‍　‍① Oral clemastine administration

via

drinking water significantly increased MBP

protein expression levels in APP/PS1+Clemastine mice than the APP/PS1 controls (

0.001). ② Clemastine administration did not alter the time proportions of NREM sleep

REM sleep and wakefulness during the daytime phase in APP/PS1 mice (

0.05). ③ Clemastine administration obviously reduced the mean firing rate of hippocampal pyramidal cells (

0.05) while increasing that of hippocampal interneurons (

0.05) in APP/PS1 mice. ④ Clemastine administration increased the occurrence rate of hippocampal sharp wave-ripple (SWR) oscillations during NREM sleep and specifically reduc

ed the firing rate of pyramidal cells during SWR oscillations in APP/PS1 mice (

0.05). ⑤ Clemastine administration had no significant effect on the hippocampal neuronal firing activity during theta oscillation in REM sleep in APP/PS1 mice (

0.05). Conclusion‍　‍Clemastine administration not only enhances the adult myelination

but also rescues both the SWRs and associated hippocampal neuronal firing during NREM sleep in APP/PS1 mice.

关键词

Keywords

references

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