Effect of two GABA-ergic drugs on the cognitive functions of rapid eye movement in sleep-deprived and recovered rats

Si, Lengge; Wang, Yuehong; Wuyun, Gerile; Bo, Agula

doi:10.3892/etm.2016.3445

Cited by 5 publications

(5 citation statements)

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“…The inhibitory effect of GABA on nerve cells is mainly achieved by stimulating the GABA A receptor (GABA A R), which is a drug target for benzodiazepines against insomnia, anxiety, and withdrawal symptoms (Gielen, Lumb, & Smart, 2012). Animal experiments have shown that increased GABA content in cerebrospinal fluid can prolong the sleep duration of cats (Gottesmann, 2002); whereas rats with rapid eye movement sleep deprivation have increased GABA content in the brain, which is considered an auto-regulatory mechanism of animals with sleep deficit (Bao, Si, Wang, Wuyun, & Bo, 2016). In sum, both clinical and animal experiments have demonstrated the therapeutic significance of increased GABA content in patients with sleep disorders (Scalise et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

The Effect of sequential bilateral low‐frequency rTMS over dorsolateral prefrontal cortex on serum level of BDNF and GABA in patients with primary insomnia

Feng

Zhang

et al. 2019

Brain and Behavior

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Objective This study aimed to investigate the effect of sequential bilateral low‐frequency repetitive transcranial magnetic stimulation (rTMS) over dorsolateral prefrontal cortex (DLPFC) on patients with primary insomnia (PI). Methods A total of 32 eligible right‐handed participants diagnosed by PI according to International classification of sleep disorders (ICD‐3) were recruited into this study. Participants received 10 daily sessions of sequential bilateral 1 Hz rTMS over DLPFC. Before and after the whole procedure of rTMS, patients were assessed by Pittsburgh Sleep Quality Index (PSQI) for the severity of sleep disturbance. Meanwhile, serum concentration of brain‐derived neurotrophic factor (BDNF) and gamma‐aminobutyric acid (GABA) in patients was measured by ELISA and UPLC, respectively. Moreover, the amplitude of MEPs reflecting the right cortical excitability was examined. Finally, Pearson correlation analysis was performed to evaluate the correlation among the change of these variables. Results After rTMS treatment, the PSQI score was markedly decreased as compared to pre‐rTMS; the concentrations of serum BDNF and GABA were significantly higher; the amplitude of MEPs was markedly reduced. Pearson correlation analysis revealed that the change of PSQI score was negatively associated with the alteration of serum BDNF level and serum GABA level, and positively associated with the change of MEPs amplitude; the change of MEPs amplitude was negatively associated with fold change in the serum BDNF level and the serum GABA level; the increase in serum GABA level was positively associated with the serum BDNF level. Conclusions A sequential bilateral low‐frequency rTMS over DLPFC significantly improves primary insomnia probably by increasing the level of BDNF and GABA in the brain and reducing cortical excitability.

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Section: Introductionmentioning

confidence: 99%

The Effect of sequential bilateral low‐frequency rTMS over dorsolateral prefrontal cortex on serum level of BDNF and GABA in patients with primary insomnia

Feng

Zhang

et al. 2019

Brain and Behavior

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“…In the clinic, numerous subjects suffer from chronic insomnia. In order to investigate this condition, modified multiple separate platforms surrounded by water have been used to prepare acute sleep deprivation or chronic sleep restriction models in various studies (7)(8)(9)(10)(11). However, to the best of our knowledge, chronic sleep deprivation models involving modified multiple platforms have not previously been reported.…”

Section: Discussionmentioning

confidence: 99%

“…DE-QI YAN 1 , XING-PING ZHANG 1,2 , WEN-HUI ZHANG 1 , NING DENG 1 , ZHENG-TING LIANG 1 , TAO LIU 2 , GUAN-YING WANG 1 , QIAN-WEI YAO 1 , KAI-KAI WANG 1 and ZHEN-PENG TONG 1 Modified multiple platforms surrounded by water have been frequently been utilized to deprive rats or mice of rapid eye movement (REM) sleep for 24-120 h (7)(8)(9)(10)(11). This method is mainly suitable for the preparation of acute insomnia models with 24 h sleep deprivation per day (12,13).…”

Section: Establishment Of a Chronic Insomnia Rat Model Of Sleep Fragm...mentioning

confidence: 99%

“…Insomnia is accompanied by daytime dysfunction in learning, memory, driving and communication, with sleepiness and napping. The Morris water maze training and test experiment is a method used to evaluate the learning and memory function of rats (10). Pentobarbital sodium-induced sleep is often used in the evaluation of animal sleep (22)(23)(24).…”

Section: Establishment Of a Chronic Insomnia Rat Model Of Sleep Fragm...mentioning

confidence: 99%

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Establishment of a chronic insomnia rat model of sleep fragmentation using unstable platforms surrounded by water

Yan

Zhang

et al. 2023

Exp Ther Med

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Chronic fragmented sleep is a very common type of insomnia that affects the daily lives of numerous people around the world. However, its pathogenesis is not very clear and a corresponding rat model has not been reported for this purpose at present. The present study aimed to establish a rat model of chronic insomnia with sleep fragmentation using self-made multiple strings of unstable platforms surrounded by shallow water. During the establishment of the models, changes in body weight and differences in food and water intake in the daytime and at night were acquired. The rat models were assessed using several tests, including the Morris water maze test, pentobarbital sodium-induced sleep, infrared monitoring and electroencephalogram/electromyography during sleep. The expression levels of certain inflammatory factors and orexin A were detected in the serum and brain tissues using ELISAs, immunohistochemistry and immunofluorescence. The expression levels of orexin 1 receptor (orexin 1r) were also detected in the brain. Polysomnography indicated that the model rats were successfully prepared with reduced non-rapid eye movement (non-REM) sleep in the daytime, which was increased at night, and considerably lower REM duration during the day and night. The number of instances of sleep arousals were also increased in the day and at night, and the average duration of each sleep bout was decreased in the daytime. The body weights of the model rats increased at a normal rate. However, the reduction of body weight in the daytime and increased in body weight at night were significantly less than those of the control rats. The daytime food and water consumption of the model rats increased significantly compared with that of the control rats, but was similar to that of the control group at night. The Morris water maze test indicated that the model rats were slow to learn to escape the platforms and performed a lower number of target crossings. The pentobarbital-induced sleep experiment confirmed that the model rats exhibited a longer sleep latency and shorter sleep time. The serum IL-1β, IL-6, TNF-α and orexin A levels of the model rats were significantly increased, whereas their serum IL-10 levels were significantly decreased compared with those of the control rats. The expression levels of IL-1β, IL-6, orexin A and orexin 1r in the brain tissues of the model rats were also significantly increased. In conclusion, these data indicate that learning and memory function, sleep time, arousal times, diurnal and nocturnal body weight changes, food and water intake, and expression levels of the specific inflammatory factors orexin A and orexin 1r were altered in the model rats. This suggests the chronic insomnia rat model with sleep fragmentation was successfully established using multiple strings of unstable platforms surrounded by water.

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“…In the CNS [23], IGF-1 is widely distributed in cortex, hippocampus and other brain regions closely related to cognitive function [24]. Previous studies have shown that mice exposed to sevo urane will present with spatial learning and memory ability impairment, but the addition of exogenous IGF-1 can improve this cognitive impairment [25]. In an animal model of traumatic brain injury, continuous lateral ventricle injection of IGF-1 for seven days after trauma led to neural restructuring and the movement function of mice and cognitive function were improved [26].…”

Section: Discussionmentioning

confidence: 99%

Role of IGF-1 in Neuroinflammation and Cogniton Deficits Induced by Sleep Deprivation

Wan

Gao²,

Zhou

et al. 2021

Preprint

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Background: Sleep deprivation negatively influences cognition, although inflammatory and immune responses participate in sleep deprivation,the molecular regulators of neuroinflammation after sleep deprivation remain to be defined. IGF-1 have shown anti-inflammatory and neuroprotective properties in models of CNS injury. This study investigated the role of IGF-1 on neuroinflammation and cognition deficits after sleep deprivation.Methods: Human periphery blood were obtained from chronic insomia(CI) patients to evaluated the levels of IGF-1. Mouse model of modified multiple platforms method (MMPM) was used to examine the role of IGF-1 in sleep deprivation. Behavior was evaluated by water maze tests.Inflammatory markers, and neuroinflammation were assessed by western blot and quantitative real-time PCR.Results: We found down-regulation of IGF-1 in human peripheral blood and in mice subjected to sleep deprivation for 5 days, and reduced activation of downstream the PI3K/AKT/GSK-3β pathway in mice brain. In conjunction, we found reduced levels of anti-apoptosis enzyme Bcl-2 and increased levels of pro-apoptosis enzyme Caspase-9, together with increased pro-inflammatory factors. Administration of IGF-1 induced activation of the PI3K/AKT/GSK-3β pathway, reversed changes in Bcl-2, Caspase-9 and pro-inflammatory factors, and prevented cognitive decline.Conclusion: These findings indicate that the IGF-1 reduces neuroinflammation and cogniton deficits after sleep deprivation. The effects may be mediated by the interaction among IGF-1 and PI3K/AKT/GSK-3β signaling. IGF-1 may be a viable therapeutic target that requires further investigations in sleep deprivation.

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Effect of two GABA-ergic drugs on the cognitive functions of rapid eye movement in sleep-deprived and recovered rats

Cited by 5 publications

References 36 publications

The Effect of sequential bilateral low‐frequency rTMS over dorsolateral prefrontal cortex on serum level of BDNF and GABA in patients with primary insomnia

The Effect of sequential bilateral low‐frequency rTMS over dorsolateral prefrontal cortex on serum level of BDNF and GABA in patients with primary insomnia

Establishment of a chronic insomnia rat model of sleep fragmentation using unstable platforms surrounded by water

Role of IGF-1 in Neuroinflammation and Cogniton Deficits Induced by Sleep Deprivation

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