Skip to main content
Top
Published in: Sleep and Breathing 1/2023

21-03-2022 | Propofol | Sleep Breathing Physiology and Disorders • Original Article

Propofol-induced sleep ameliorates cognition impairment in sleep-deprived rats

Authors: Yizhi Lu, Yong Xiao, Youbing Tu, Weixin Dai, Yubo Xie

Published in: Sleep and Breathing | Issue 1/2023

Login to get access

Abstract

Purpose

Propofol has been shown to clear sleep debt in rats after sleep deprivation (SD). We examined whether or not propofol-assisted sleep can restore cognitive function in SD rats and explored the possible mechanisms.

Methods

A sleep deprivation model was established by housing 9 to 12 week-old rats to a multiplatform water tank for 96 h. Model rats were then intraperitoneally injected with different concentrations of propofol or 10% fat emulsion (vehicle control). All treatment groups were examined for spatial learning and memory ability in the Morris water maze (MWM). After euthanasia, morphological changes in the hippocampus, hippocampal neurons, and mitochondria were examined by hematoxylin–eosin staining and transmission electron microscopy. Serum and hippocampal levels of IL-1β, TNF-α, and hippocampal concentrations of ATP and Cyt-c were measured by ELISA (enzyme-linked immunosorbent assay). Immunohistochemistry and Western blotting were performed to assess hippocampal expression of Bcl-2, Bax, and cleaved caspase-3.

Results

Results showed that escape latencies in MWM training trials were significantly shorter and target crossings in the memory probe trial significantly greater in propofol-treated SD model rats compared to vehicle-treated SD rats. Propofol also reduced the number of apoptotic bodies in the hippocampal CA1 region. Sleep deprivation reduced IL-1β and ATP in hippocampus while increasing TNF-α and Cyt-c, and propofol treatment reversed all these changes. There was no significant difference in Bcl-2 expression between propofol- and vehicle-treated SD rats, but pro-apoptotic Bax and cleaved caspase-3 expression levels were significantly reduced by propofol in SD rats.

Conclusions

Propofol-assisted sleep restored cognitive function in SD rats possibly by attenuating mitochondria-mediated neuronal apoptosis in the hippocampus.
Appendix
Available only for authorised users
Literature
1.
go back to reference Krause AJ, Simon EB, Mander BA, Greer SM, Saletin JM, Goldstein-Piekarski AN, Walker MP (2017) The sleep-deprived human brain. Nat Rev Neurosci 18(7):404–418PubMedPubMedCentralCrossRef Krause AJ, Simon EB, Mander BA, Greer SM, Saletin JM, Goldstein-Piekarski AN, Walker MP (2017) The sleep-deprived human brain. Nat Rev Neurosci 18(7):404–418PubMedPubMedCentralCrossRef
2.
3.
go back to reference Pisani MA, Friese RS, Gehlbach BK, Schwab RJ, Weinhouse GL, Jones SF (2015) Sleep in the intensive care unit. Am J Respir Crit Care Med 191(7):731–738PubMedPubMedCentralCrossRef Pisani MA, Friese RS, Gehlbach BK, Schwab RJ, Weinhouse GL, Jones SF (2015) Sleep in the intensive care unit. Am J Respir Crit Care Med 191(7):731–738PubMedPubMedCentralCrossRef
4.
go back to reference Fadayomi AB, Ibala R, Bilotta F, Westover MB, Akeju O (2018) A systematic review and meta-analysis examining the impact of sleep disturbance on postoperative delirium. Crit Care Med 46(12):e1204–e1212PubMedPubMedCentralCrossRef Fadayomi AB, Ibala R, Bilotta F, Westover MB, Akeju O (2018) A systematic review and meta-analysis examining the impact of sleep disturbance on postoperative delirium. Crit Care Med 46(12):e1204–e1212PubMedPubMedCentralCrossRef
5.
go back to reference Winkelman JW (2015) Clinical practice. Insomnia disorder N Engl J Med 373(15):1437–1444PubMed Winkelman JW (2015) Clinical practice. Insomnia disorder N Engl J Med 373(15):1437–1444PubMed
6.
go back to reference Luppi PH, Peyron C, Fort P (2017) Not a single but multiple populations of GABAergic neurons control sleep. Sleep Med Rev 32:85–94PubMedCrossRef Luppi PH, Peyron C, Fort P (2017) Not a single but multiple populations of GABAergic neurons control sleep. Sleep Med Rev 32:85–94PubMedCrossRef
7.
go back to reference Atkin T, Comai S, Gobbi G (2018) Drugs for insomnia beyond benzodiazepines: pharmacology, clinical applications, and discovery. Pharmacol Rev 70(2):197–245PubMedCrossRef Atkin T, Comai S, Gobbi G (2018) Drugs for insomnia beyond benzodiazepines: pharmacology, clinical applications, and discovery. Pharmacol Rev 70(2):197–245PubMedCrossRef
8.
go back to reference Franks NP (2008) General anaesthesia: from molecular targets to neuronal pathways of sleep and arousal. Nat Rev Neurosci 9(5):370–386PubMedCrossRef Franks NP (2008) General anaesthesia: from molecular targets to neuronal pathways of sleep and arousal. Nat Rev Neurosci 9(5):370–386PubMedCrossRef
9.
10.
go back to reference Bola M, Barrett AB, Pigorini A, Nobili L, Seth AK, Marchewka A (2018) Loss of consciousness is related to hyper-correlated gamma-band activity in anesthetized macaques and sleeping humans. Neuroimage 167:130–142PubMedCrossRef Bola M, Barrett AB, Pigorini A, Nobili L, Seth AK, Marchewka A (2018) Loss of consciousness is related to hyper-correlated gamma-band activity in anesthetized macaques and sleeping humans. Neuroimage 167:130–142PubMedCrossRef
11.
go back to reference Murphy M, Bruno MA, Riedner BA, Boveroux P, Noirhomme Q, Landsness EC, Brichant JF, Phillips C, Massimini M, Laureys S, Tononi G, Boly M (2011) Propofol anesthesia and sleep: a high-density EEG study. Sleep 34(3):283–291PubMedPubMedCentralCrossRef Murphy M, Bruno MA, Riedner BA, Boveroux P, Noirhomme Q, Landsness EC, Brichant JF, Phillips C, Massimini M, Laureys S, Tononi G, Boly M (2011) Propofol anesthesia and sleep: a high-density EEG study. Sleep 34(3):283–291PubMedPubMedCentralCrossRef
12.
go back to reference Luo T, Wu J, Kabadi SV, Sabirzhanov B, Guanciale K, Hanscom M, Faden J, Cardiff K, Bengson CJ, Faden AI (2013) Propofol limits microglial activation after experimental brain trauma through inhibition of nicotinamide adenine dinucleotide phosphate oxidase. Anesthesiology 119(6):1370–1388PubMedCrossRef Luo T, Wu J, Kabadi SV, Sabirzhanov B, Guanciale K, Hanscom M, Faden J, Cardiff K, Bengson CJ, Faden AI (2013) Propofol limits microglial activation after experimental brain trauma through inhibition of nicotinamide adenine dinucleotide phosphate oxidase. Anesthesiology 119(6):1370–1388PubMedCrossRef
13.
go back to reference Tung A, Lynch JP, Mendelson WB (2001) Prolonged sedation with propofol in the rat does not result in sleep deprivation. Anesth Analg 92(5):1232–1236PubMedCrossRef Tung A, Lynch JP, Mendelson WB (2001) Prolonged sedation with propofol in the rat does not result in sleep deprivation. Anesth Analg 92(5):1232–1236PubMedCrossRef
14.
go back to reference Treggiari-Venzi M, Borgeat A, Fuchs-Buder T, Gachoud JP, Suter PM (1996) Overnight sedation with midazolam or propofol in the ICU: effects on sleep quality, anxiety and depression. Intensive Care Med 22(11):1186–1190PubMedCrossRef Treggiari-Venzi M, Borgeat A, Fuchs-Buder T, Gachoud JP, Suter PM (1996) Overnight sedation with midazolam or propofol in the ICU: effects on sleep quality, anxiety and depression. Intensive Care Med 22(11):1186–1190PubMedCrossRef
15.
go back to reference Xu Z, Jiang X, Li W, Gao D, Li X, Liu J (2011) Propofol-induced sleep: efficacy and safety in patients with refractory chronic primary insomnia. Cell Biochem Biophys 60(3):161–166PubMedCrossRef Xu Z, Jiang X, Li W, Gao D, Li X, Liu J (2011) Propofol-induced sleep: efficacy and safety in patients with refractory chronic primary insomnia. Cell Biochem Biophys 60(3):161–166PubMedCrossRef
17.
go back to reference Guzman-Marin R, Suntsova N, Bashir T, Nienhuis R, Szymusiak R, McGinty D (2008) Rapid eye movement sleep deprivation contributes to reduction of neurogenesis in the hippocampal dentate gyrus of the adult rat. Sleep 31(2):167–175PubMedPubMedCentralCrossRef Guzman-Marin R, Suntsova N, Bashir T, Nienhuis R, Szymusiak R, McGinty D (2008) Rapid eye movement sleep deprivation contributes to reduction of neurogenesis in the hippocampal dentate gyrus of the adult rat. Sleep 31(2):167–175PubMedPubMedCentralCrossRef
18.
go back to reference Soto-Rodriguez S, Lopez-Armas G, Luquin S et al (2016) Rapid eye movement sleep deprivation produces long-term detrimental effects in spatial memory and modifies the cellular composition of the subgranular zone. Front Cell Neurosci 10:132PubMedPubMedCentralCrossRef Soto-Rodriguez S, Lopez-Armas G, Luquin S et al (2016) Rapid eye movement sleep deprivation produces long-term detrimental effects in spatial memory and modifies the cellular composition of the subgranular zone. Front Cell Neurosci 10:132PubMedPubMedCentralCrossRef
19.
go back to reference Yang SQ, Jiang L, Lan F, Wei HJ, Xie M, Zou W, Zhang P, Wang CY, Xie YR, Tang XQ (2019) Inhibited endogenous H2S generation and excessive autophagy in hippocampus contribute to sleep deprivation-induced cognitive impairment. Front Psychol 10:53PubMedPubMedCentralCrossRef Yang SQ, Jiang L, Lan F, Wei HJ, Xie M, Zou W, Zhang P, Wang CY, Xie YR, Tang XQ (2019) Inhibited endogenous H2S generation and excessive autophagy in hippocampus contribute to sleep deprivation-induced cognitive impairment. Front Psychol 10:53PubMedPubMedCentralCrossRef
20.
go back to reference Toda H, Williams JA, Gulledge M, Sehgal A (2019) A sleep-inducing gene, nemuri, links sleep and immune function in Drosophila. Science 363(6426):509–515PubMedPubMedCentralCrossRef Toda H, Williams JA, Gulledge M, Sehgal A (2019) A sleep-inducing gene, nemuri, links sleep and immune function in Drosophila. Science 363(6426):509–515PubMedPubMedCentralCrossRef
21.
go back to reference Pandey AK, Kar SK (2011) REM sleep deprivation of rats induces acute phase response in liver. Biochem Biophys Res Commun 410(2):242–246PubMedCrossRef Pandey AK, Kar SK (2011) REM sleep deprivation of rats induces acute phase response in liver. Biochem Biophys Res Commun 410(2):242–246PubMedCrossRef
22.
go back to reference Parekh PJ, Oldfield Iv EC, Challapallisri V, Ware JC, Johnson DA (2015) Sleep disorders and inflammatory disease activity: chicken or the egg? Am J Gastroenterol 110(4):484–488PubMedCrossRef Parekh PJ, Oldfield Iv EC, Challapallisri V, Ware JC, Johnson DA (2015) Sleep disorders and inflammatory disease activity: chicken or the egg? Am J Gastroenterol 110(4):484–488PubMedCrossRef
24.
go back to reference Simi A, Lerouet D, Pinteaux E, Brough D (2007) Mechanisms of regulation for interleukin-1beta in neurodegenerative disease. Neuropharmacology 52(8):1563–1569PubMedCrossRef Simi A, Lerouet D, Pinteaux E, Brough D (2007) Mechanisms of regulation for interleukin-1beta in neurodegenerative disease. Neuropharmacology 52(8):1563–1569PubMedCrossRef
25.
go back to reference Song XM, Wang YL, Li JG, Wang CY, Zhou Q, Zhang ZZ, Liang H (2009) Effects of propofol on pro-inflammatory cytokines and nuclear factor kappaB during polymicrobial sepsis in rats. Mol Biol Rep 36(8):2345–2351PubMedCrossRef Song XM, Wang YL, Li JG, Wang CY, Zhou Q, Zhang ZZ, Liang H (2009) Effects of propofol on pro-inflammatory cytokines and nuclear factor kappaB during polymicrobial sepsis in rats. Mol Biol Rep 36(8):2345–2351PubMedCrossRef
27.
go back to reference Krueger JM, Obál FJ, Fang J, Kubota T, Taishi P (2001) The role of cytokines in physiological sleep regulation. Ann N Y Acad Sci 933:211–221PubMedCrossRef Krueger JM, Obál FJ, Fang J, Kubota T, Taishi P (2001) The role of cytokines in physiological sleep regulation. Ann N Y Acad Sci 933:211–221PubMedCrossRef
28.
go back to reference Maurer SV, Williams CL (2017) The cholinergic system modulates memory and hippocampal plasticity via its interactions with non-neuronal cells. Front Immunol 8:1489PubMedPubMedCentralCrossRef Maurer SV, Williams CL (2017) The cholinergic system modulates memory and hippocampal plasticity via its interactions with non-neuronal cells. Front Immunol 8:1489PubMedPubMedCentralCrossRef
29.
go back to reference Mohammed HS, Khadrawy YA (2021) Electrophysiological and neurochemical evaluation of the adverse effects of REM sleep deprivation and epileptic seizures on rat’s brain. Life Sci 273:119303PubMedCrossRef Mohammed HS, Khadrawy YA (2021) Electrophysiological and neurochemical evaluation of the adverse effects of REM sleep deprivation and epileptic seizures on rat’s brain. Life Sci 273:119303PubMedCrossRef
30.
go back to reference Yirmiya R, Winocur G, Goshen I (2002) Brain interleukin-1 is involved in spatial memory and passive avoidance conditioning. Neurobiol Learn Mem 78(2):379–389PubMedCrossRef Yirmiya R, Winocur G, Goshen I (2002) Brain interleukin-1 is involved in spatial memory and passive avoidance conditioning. Neurobiol Learn Mem 78(2):379–389PubMedCrossRef
31.
go back to reference Barrientos RM, Sprunger DB, Campeau S, Watkins LR, Rudy JW, Maier SF (2004) BDNF mRNA expression in rat hippocampus following contextual learning is blocked by intrahippocampal IL-1beta administration. J Neuroimmunol 155(1–2):119–126PubMedCrossRef Barrientos RM, Sprunger DB, Campeau S, Watkins LR, Rudy JW, Maier SF (2004) BDNF mRNA expression in rat hippocampus following contextual learning is blocked by intrahippocampal IL-1beta administration. J Neuroimmunol 155(1–2):119–126PubMedCrossRef
32.
go back to reference McGinty D, Szymusiak R (2001) Brain structures and mechanisms involved in the generation of NREM sleep: focus on the preoptic hypothalamus. Sleep Med Rev 5(4):323–342PubMedCrossRef McGinty D, Szymusiak R (2001) Brain structures and mechanisms involved in the generation of NREM sleep: focus on the preoptic hypothalamus. Sleep Med Rev 5(4):323–342PubMedCrossRef
33.
go back to reference Perosa V, Priester A, Ziegler G, Cardenas-Blanco A, Dobisch L, Spallazzi M, Assmann A, Maass A, Speck O, Oltmer J, Heinze HJ, Schreiber S, Düzel E (2020) Hippocampal vascular reserve associated with cognitive performance and hippocampal volume. Brain 143(2):622–634PubMedPubMedCentralCrossRef Perosa V, Priester A, Ziegler G, Cardenas-Blanco A, Dobisch L, Spallazzi M, Assmann A, Maass A, Speck O, Oltmer J, Heinze HJ, Schreiber S, Düzel E (2020) Hippocampal vascular reserve associated with cognitive performance and hippocampal volume. Brain 143(2):622–634PubMedPubMedCentralCrossRef
34.
go back to reference Boyman L, Karbowski M, Lederer WJ (2020) Regulation of mitochondrial ATP production: Ca2+ signaling and quality control. Trends Mol Med 26(1):21–39PubMedCrossRef Boyman L, Karbowski M, Lederer WJ (2020) Regulation of mitochondrial ATP production: Ca2+ signaling and quality control. Trends Mol Med 26(1):21–39PubMedCrossRef
35.
go back to reference Ham SJ, Lee D, Yoo H, Jun K, Shin H, Chung J (2020) Decision between mitophagy and apoptosis by Parkin via VDAC1 ubiquitination. Proc Natl Acad Sci U S A 117(8):4281–4291PubMedPubMedCentralCrossRef Ham SJ, Lee D, Yoo H, Jun K, Shin H, Chung J (2020) Decision between mitophagy and apoptosis by Parkin via VDAC1 ubiquitination. Proc Natl Acad Sci U S A 117(8):4281–4291PubMedPubMedCentralCrossRef
36.
go back to reference Baud MO, Parafita J, Nguyen A, Magistretti PJ, Petit JM (2016) Sleep fragmentation alters brain energy metabolism without modifying hippocampal electrophysiological response to novelty exposure. J Sleep Res 25(5):583–590PubMedCrossRef Baud MO, Parafita J, Nguyen A, Magistretti PJ, Petit JM (2016) Sleep fragmentation alters brain energy metabolism without modifying hippocampal electrophysiological response to novelty exposure. J Sleep Res 25(5):583–590PubMedCrossRef
37.
go back to reference Taylor RC, Cullen SP, Martin SJ (2008) Apoptosis: controlled demolition at the cellular level. Nat Rev Mol Cell Biol 9(3):231–241PubMedCrossRef Taylor RC, Cullen SP, Martin SJ (2008) Apoptosis: controlled demolition at the cellular level. Nat Rev Mol Cell Biol 9(3):231–241PubMedCrossRef
38.
go back to reference Yang RH, Hu SJ, Wang Y, Zhang WB, Luo WJ, Chen JY (2008) Paradoxical sleep deprivation impairs spatial learning and affects membrane excitability and mitochondrial protein in the hippocampus. Brain Res 1230:224–232PubMedCrossRef Yang RH, Hu SJ, Wang Y, Zhang WB, Luo WJ, Chen JY (2008) Paradoxical sleep deprivation impairs spatial learning and affects membrane excitability and mitochondrial protein in the hippocampus. Brain Res 1230:224–232PubMedCrossRef
39.
go back to reference Liu J, Liu W, Lu Y, Tian H, Duan C, Lu L, Gao G, Wu X, Wang X, Yang H (2018) Piperlongumine restores the balance of autophagy and apoptosis by increasing BCL2 phosphorylation in rotenone-induced Parkinson disease models. Autophagy 14(5):845–861PubMedPubMedCentralCrossRef Liu J, Liu W, Lu Y, Tian H, Duan C, Lu L, Gao G, Wu X, Wang X, Yang H (2018) Piperlongumine restores the balance of autophagy and apoptosis by increasing BCL2 phosphorylation in rotenone-induced Parkinson disease models. Autophagy 14(5):845–861PubMedPubMedCentralCrossRef
41.
go back to reference de Souza L, Smaili SS, Ureshino RP, Sinigaglia-Coimbra R, Andersen ML, Lopes GS, Tufik S (2012) Effect of chronic sleep restriction and aging on calcium signaling and apoptosis in the hippocampus of young and aged animals. Prog Neuropsychopharmacol Biol Psychiatry 39(1):23–30PubMedCrossRef de Souza L, Smaili SS, Ureshino RP, Sinigaglia-Coimbra R, Andersen ML, Lopes GS, Tufik S (2012) Effect of chronic sleep restriction and aging on calcium signaling and apoptosis in the hippocampus of young and aged animals. Prog Neuropsychopharmacol Biol Psychiatry 39(1):23–30PubMedCrossRef
42.
go back to reference Montes-Rodríguez CJ, Alavez S, Soria-Gómez E, Rueda-Orozco PE, Guzman K, Morán J, Prospéro-García O (2009) BCL-2 and BAX proteins expression throughout the light-dark cycle and modifications induced by sleep deprivation and rebound in adult rat brain. J Neurosci Res 87(7):1602–1609PubMedCrossRef Montes-Rodríguez CJ, Alavez S, Soria-Gómez E, Rueda-Orozco PE, Guzman K, Morán J, Prospéro-García O (2009) BCL-2 and BAX proteins expression throughout the light-dark cycle and modifications induced by sleep deprivation and rebound in adult rat brain. J Neurosci Res 87(7):1602–1609PubMedCrossRef
43.
go back to reference Yang Y, Zong Y, Sun Q, Jia Y, Zhao R (2017) White light emitting diode suppresses proliferation and induces apoptosis in hippocampal neuron cells through mitochondrial cytochrome c oxydase-mediated IGF-1 and TNF-α pathways. Free Radic Biol Med 113:413–423PubMedCrossRef Yang Y, Zong Y, Sun Q, Jia Y, Zhao R (2017) White light emitting diode suppresses proliferation and induces apoptosis in hippocampal neuron cells through mitochondrial cytochrome c oxydase-mediated IGF-1 and TNF-α pathways. Free Radic Biol Med 113:413–423PubMedCrossRef
Metadata
Title
Propofol-induced sleep ameliorates cognition impairment in sleep-deprived rats
Authors
Yizhi Lu
Yong Xiao
Youbing Tu
Weixin Dai
Yubo Xie
Publication date
21-03-2022
Publisher
Springer International Publishing
Keyword
Propofol
Published in
Sleep and Breathing / Issue 1/2023
Print ISSN: 1520-9512
Electronic ISSN: 1522-1709
DOI
https://doi.org/10.1007/s11325-022-02591-5

Other articles of this Issue 1/2023

Sleep and Breathing 1/2023 Go to the issue

Epidemiology • Original Article

Sleep quality in men with androgenetic alopecia

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine
Webinar | 06-02-2024 | 20:00 (CET)

Mastering chronic pancreatitis pain: A multidisciplinary approach and practical solutions

Severe pain is the most common symptom of chronic pancreatitis. In this webinar, experts share the latest insights in pain management for chronic pancreatitis patients. Experts from a range of disciplines discuss pertinent cases and provide practical suggestions for use within clinical practice.

Sponsored by: Viatris

Developed by: Springer Healthcare