Objective: To explore the correlation between the changes of cognitive function and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway in rats after sleep deprivation (SD), and to provide a reference for the subsequent exploration of the pathogenesis of insomnia. Methods: The 8-week-old SD rats were used as the research object. After 1 week of adaptive feeding, they were randomly divided into 2 groups, with 10 rats in each group. The control group and the chronic sleep deprivation group (experimental group) were subjected to sleep deprivation by modified multi-platform water environment method. Morris water maze was used to detect the cognitive function of all rats. Western blot analysis was used to detect the expression of P-PI3K, P-Akt, P-mTOR, Beclin-1 and Caspase-3 protein in hippocampus. Results: Compared with the control group, the escape latency on the fifth day of the experimental group was significantly prolonged (P＜0.01), the number of times through the platform was reduced (P＜0.05), and the time spent in the target quadrant was reduced (P＜0.05). The expression of P-PI3 K, P-Akt and P-mTOR protein in hippocampus of rats was significantly decreased (P＜0.01), the expression of autophagy-related protein Beclin-1 was increased (P＜0.01), and the expression of apoptosis-related protein Caspase was increased (P＜0.01), the difference was statistically significant. Conclusion: (1)The expression of P-PI3K、P-Akt and P-mTOR in hippocampus of rats after 7 days of sleep deprivation is lower than that of normal rats, and the ability of spatial learning and memory is decreased. It is speculated that the cognitive impairment after chronic sleep deprivation in rats may be related to the inhibition of PI3K/Akt/mTOR signaling pathway; (2)The expression of autophagy-related protein Beclin-1 and apoptotic protein Caspase-3 in hippocampus of rats after 7 days of sleep deprivation is higher than that of normal rats.
YANG Zhen
,
LIU Bo
. The mechanism of PI3K/Akt/mTOR signaling pathway in cognitive impairment after chronic sleep deprivation[J]. Journal of Baotou Medical College, 2025
, 41(2)
: 24
-28
.
DOI: 10.16833/j.cnki.jbmc.2025.02.005
[1] Liew SC, Aung T. Sleep deprivation and its association with diseases- a review[J]. Sleep Med, 2021, 77: 192-204.
[2] Aho V, Ollila HM, Kronholm E, et al. Prolonged sleep restriction induces changes in pathways involved in cholesterol metabolism and inflammatory responses[J]. Sci Rep, 2016, 6: 24828.
[3] Rault C, Sangaré A, Diaz V, et al. Impact of sleep deprivation on respiratory motor output and endurance. A physiological study[J]. Am J Respir Crit Care Med, 2020, 201(8): 976-983.
[4] Geoffroy PA, Hoertel N, Etain B, et al. Insomnia and hypersomnia in major depressive episode: prevalence, sociodemographic characteristics and psychiatric comorbidity in a population-based study[J]. J Affect Disord, 2018, 226: 132-141.
[5] Xu F, Na LX, Li YF, et al. Retracted article: roles of the PI3K/AKT/mTOR signalling pathways in neurodegenerative diseases and tumours[J]. Cell Biosci, 2020, 10(1): 54.
[6] Briggs CE, Wang YL, Kong B, et al. Midbrain dopamine neurons in Parkinson′s disease exhibit a dysregulated miRNA and target-gene network[J]. Brain Res, 2015, 1618: 111-121.
[7] Wei XY, Luo LF, Chen JZ. Roles of mTOR signaling in tissue regeneration[J]. Cells, 2019, 8(9): 1075.
[8] Heras-Sandoval D, Pérez-Rojas JM, Hernández-Damián J, et al. The role of PI3K/AKT/mTOR pathway in the modulation of autophagy and the clearance of protein aggregates in neurodegeneration[J]. Cell Signal, 2014, 26(12): 2694-2701.
[9] Zhang WY, Zhang W, Dai N, et al. A rat model of central fatigue using a modified multiple platform method[J]. JoVE, 2018(138): 57362.
[10] 高微. 海马IGF-1/PI3K/Akt信号通路在小鼠REM睡眠剥夺后认知功能损伤机制中的作用[D]. 天津:天津医科大学, 2019.
[11] Xue R, Wan YH, Sun XQ, et al. Nicotinic mitigation of neuroinflammation and oxidative stress after chronic sleep deprivation[J].Front Immunol, 2019, 10: 2546.
[12] Xu J, Qi QQ, Lyu PY, et al. Oxiracetam ameliorates cognitive deficits in vascular dementia rats by regulating the expression of neuronal apoptosis/autophagy-related genes associated with the activation of the Akt/mTOR signaling pathway[J]. Braz J Med Biol Res, 2019, 52(11): e8371.
[13] Shang N, Zhang P, Wang S, et al. Aluminum-induced cognitive impairment and PI3K/akt/mTOR signaling pathway involvement in occupational aluminum workers[J]. Neurotox Res, 2020, 38(2): 344-358.
[14] Shi RY, Weng JQ, Zhao L, et al. Excessive autophagy contributes to neuron death in cerebral ischemia[J]. CNS Neurosci Ther, 2012, 18(3): 250-260.
[15] Wan YH, Gao W, Zhou KL, et al. Role of IGF-1 in neuroinflammation and cognition deficits induced by sleep deprivation[J].Neurosci Lett, 2022, 776:136575.
