Distinct behavioral and brain changes after different durations of the modified multiple platform method on rats: An animal model of central fatigue

Chenxia Han,Siyuan Guo,Yan Liu,Yuehan Song,Jie Ma,Feng Li,Weihong Li,Jing Liu,Yingqiu Mao

doi:10.1371/journal.pone.0176850

Chenxia Han, Siyuan Guo + Show 7 more

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https://doi.org/10.1371/journal.pone.0176850

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Journal: PLOS ONE	Publication Date: May 11, 2017
Citations: 8	License type: CC BY 4.0

Affiliation: Beijing University of Chinese Medicine

Abstract

The modified multiple platform method (MMPM) is a classical sleep deprivation model. It has been widely used in behavioral and brain research, due to its effects on physical and mental functions. However, different MMPM protocols can promote distinct effects in rats. Although the MMPM has been proved to induce central fatigue, the effects of different durations of subjection to the MMPM remain undetermined. This study aims to investigate the changes in behavior, N-Methyl-d-Aspartate receptor 1 (NR1) and 2A (NR2A), as well as the ultrastructural alteration in the hippocampus after different MMPM modelling, to compare the central fatigue effect induced by dynamic MMPM. Rats were randomly divided into four groups: 5-, 14- and 21- day MMPM groups, and a control group. Each MMPM group underwent a 14-hour daily MMPM modelling. After each training session, open field and elevated plus maze tests were performed. Corticosterone levels were detected by ELISA, and the hippocampal NR1 and NR2A were measured by RT-PCR and Western blot analysis. In addition, ultrastructural changes in the hippocampal cornu ammonis 1(CA1) region were determined by transmission electron microscopy (TEM). The findings showed that the 5 and 14 days of MMPM induced a high-stress state, while the 21 days of MMPM induced anxiety and degenerative alteration in the hippocampal morphology. Additionally, hippocampal NR1 and NR2A gene expression decreased in all MMPM groups, whereas the protein expression only decreased in the 21-day group. Overall, different durations of MMPM caused distinct behavioral and brain changes, and the 21 days of MMPM could induce central fatigue.

Highlights

A close relationship between the rhythm and duration of sleep and the central nervous system (CNS) function has been found[1]
The representative track of every group revealed that the 5- and 14-day modified multiple platform method (MMPM) increased the central travelling compared with control group
The present study proved that different MMPM protocols can generate distinct behavioral and brain changes, 21 days of MMPM could generate substantive anxiety without stress response, degenerative changes in hippocampal synapses and mitochondria, and down regulation of NMDA receptors, which make the condition favorable to develop central fatigue

Summary

Introduction

A close relationship between the rhythm and duration of sleep and the central nervous system (CNS) function has been found[1]. When the tank is filled with water (1-2cm to the surface of platform), rats are forced to stand on the platforms because of their instinctive fear of water, when they fall asleep, they will fall into the water and wake up[7] This method can effectively affect emotion[8,9] and cause cognitive dysfunction[10]. Previous studies found that the intermittent subjection to MMPM could induce central fatigue[14,15], and the condition could be treated by CNS function-improving medicine [16,17]. Research on this topic remains scant and needs to be enriched

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