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https://www.sciencedirect.com/science/article/pii/S0361923024000844
Brain Research Bulletin
Volume 212, 15 June 2024, 110951
Research report
Replicating human characteristics: A promising animal model of central fatigue
Highlights
Abstract
Central fatigue is a common pathological state characterized by psychological loss of drive, lack of appetite, drowsiness, and decreased psychic alertness.
The mechanism underlying central fatigue is still unclear, and there is no widely accepted successful animal model that fully represents human characteristics.
We aimed to construct a more clinically relevant and comprehensive animal model of central fatigue.
In this study, we utilized the Modified Multiple Platform Method (MMPM) combined with alternate-day fasting (ADF) to create the animal model.
The model group rats are placed on a stationary water environment platform for sleep deprivation at a fixed time each day, and they were subjected to ADF treatment.
On non-fasting days, the rats were allowed unrestricted access to food. This process was sustained over a period of 21 days.
We evaluated the model using behavioral assessments such as open field test, elevated plus maze test, tail suspension test, Morris water maze test, grip strength test, and forced swimming test, as well as serum biochemical laboratory indices.
Additionally, we conducted pathological observations of the hippocampus and quadriceps muscle tissues, transmission electron microscope observation of mitochondrial ultrastructure, and assessment of mitochondrial energy metabolism and oxidative stress-related markers.
The results revealed that the model rats displayed emotional anomalies resembling symptoms of depression and anxiety, decreased exploratory behavior, decline in learning and memory function, and signs of skeletal muscle fatigue, successfully replicating human features of negative emotions, cognitive decline, and physical fatigue.
Pathological damage and mitochondrial ultrastructural alterations were observed in the hippocampus and quadriceps muscle tissues, accompanied by abnormal mitochondrial energy metabolism and oxidative stress in the form of decreased ATP and increased ROS levels.
In conclusion, our ADF+MMPM model comprehensively replicated the features of human central fatigue and is a promising platform for preclinical research.
Furthermore, the pivotal role of mitochondrial energy metabolism and oxidative stress damage in the occurrence of central fatigue in the hippocampus and skeletal muscle tissues was corroborated.
---
Yifei Zhang, Zehan Zhang, Qingqian Yu, Bijuan Lan, Qinghuan Shi, Ruting Li, Ziheng Jiao, Weiyue Zhang, Feng Li,
Replicating human characteristics: A promising animal model of central fatigue,
Brain Research Bulletin,
Volume 212,
2024,
110951,
ISSN 0361-9230,
https://doi.org/10.1016/j.brainresbull.2024.110951.
https://www.sciencedirect.com/science/article/pii/S0361923024000844
Brain Research Bulletin
Volume 212, 15 June 2024, 110951
Research report
Replicating human characteristics: A promising animal model of central fatigue
Highlights
- •
A new method: Modified Multiple Platform Method combined with alternate-day fasting. - •
Modeling method has successfully constructed animal model of central fatigue. - •
Our rat model mimics human emotional, cognitive, and physical fatigue. - •
Hippocampus and muscle tissues show damage and mitochondrial changes. - •
Mitochondrial dysfunction and oxidative stress in hippocampus and muscle tissues.
Abstract
Central fatigue is a common pathological state characterized by psychological loss of drive, lack of appetite, drowsiness, and decreased psychic alertness.
The mechanism underlying central fatigue is still unclear, and there is no widely accepted successful animal model that fully represents human characteristics.
We aimed to construct a more clinically relevant and comprehensive animal model of central fatigue.
In this study, we utilized the Modified Multiple Platform Method (MMPM) combined with alternate-day fasting (ADF) to create the animal model.
The model group rats are placed on a stationary water environment platform for sleep deprivation at a fixed time each day, and they were subjected to ADF treatment.
On non-fasting days, the rats were allowed unrestricted access to food. This process was sustained over a period of 21 days.
We evaluated the model using behavioral assessments such as open field test, elevated plus maze test, tail suspension test, Morris water maze test, grip strength test, and forced swimming test, as well as serum biochemical laboratory indices.
Additionally, we conducted pathological observations of the hippocampus and quadriceps muscle tissues, transmission electron microscope observation of mitochondrial ultrastructure, and assessment of mitochondrial energy metabolism and oxidative stress-related markers.
The results revealed that the model rats displayed emotional anomalies resembling symptoms of depression and anxiety, decreased exploratory behavior, decline in learning and memory function, and signs of skeletal muscle fatigue, successfully replicating human features of negative emotions, cognitive decline, and physical fatigue.
Pathological damage and mitochondrial ultrastructural alterations were observed in the hippocampus and quadriceps muscle tissues, accompanied by abnormal mitochondrial energy metabolism and oxidative stress in the form of decreased ATP and increased ROS levels.
In conclusion, our ADF+MMPM model comprehensively replicated the features of human central fatigue and is a promising platform for preclinical research.
Furthermore, the pivotal role of mitochondrial energy metabolism and oxidative stress damage in the occurrence of central fatigue in the hippocampus and skeletal muscle tissues was corroborated.
---
Yifei Zhang, Zehan Zhang, Qingqian Yu, Bijuan Lan, Qinghuan Shi, Ruting Li, Ziheng Jiao, Weiyue Zhang, Feng Li,
Replicating human characteristics: A promising animal model of central fatigue,
Brain Research Bulletin,
Volume 212,
2024,
110951,
ISSN 0361-9230,
https://doi.org/10.1016/j.brainresbull.2024.110951.
