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H2S Attenuates Sleep Deprivation-Induced Cognitive Impairment by Reducing Excessive Autophagy via Hippocampal Sirt-1 in WISTAR RATS

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Abstract

Sleep deprivation (SD) is widespread in society causing serious damage to cognitive function. Hydrogen sulfide (H2S), the third gas signal molecule, plays important regulatory role in learning and memory functions. Inhibition of excessive autophagy and upregulation of silent information regulator 1 (Sirt-1) have been reported to prevent cognitive dysfunction. Therefore, this present work was to address whether H2S attenuates the cognitive impairment induced by SD in Wistar rats and whether the underlying mechanisms involve in inhibition of excessive autophagy and upregulation of Sirt-1. After treatment with SD for 72 h, the cognitive function of Wistar rats was evaluated by Y-maze, new object recognition, object location, and Morris water maze tests. The results shown that SD-caused cognitive impairment was reversed by treatment with NaHS (a donor of H2S). NaHS also prevented SD-induced hippocampal excessive autophagy, as evidenced by the decrease in autophagosomes, the down-regulation of Beclin1, and the up-regulation of p62 in the hippocampus of SD-exposed Wistar rats. Furthermore, Sirtinol, an inhibitor of Sirt-1, reversed the inhibitory roles of NaHS in SD-induced cognitive impairment and excessive hippocampal autophagy in Wistar rats. Taken together, our results suggested that H2S improves the cognitive function of SD-exposed rats by inhibiting excessive hippocampal autophagy in a hippocampal Sirt-1-dependent way.

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Data Availability

The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. Koyanagi I, Akers KG, Vergara P, Srinivasan S, Sakurai T, Sakaguchi M (2019) Memory consolidation during sleep and adult hippocampal neurogenesis. Neural Regen Res 14:20–23

    PubMed  PubMed Central  Google Scholar 

  2. Chee MWL, Zhou J (2019) Functional connectivity and the sleep-deprived brain. Prog Brain Res 246:159–176

    PubMed  Google Scholar 

  3. Feng L, Wu HW, Song GQ, Lu C, Li YH, Qu LN, Chen SG, Liu XM, Chang Q (2016) Chronical sleep interruption-induced cognitive decline assessed by a metabolomics method. Behav Brain Res 302:60–68

    CAS  PubMed  Google Scholar 

  4. Bubu OM, Brannick M, Mortimer J, Umasabor-Bubu O, Sebastiao YV, Wen Y, Schwartz S, Borenstein AR, Wu Y, Morgan D, Anderson WM (2017) Sleep, cognitive impairment, and Alzheimer’s disease: a systematic review and meta-analysis. Sleep 40:1–18

    Google Scholar 

  5. Havekes R, Vecsey CG, Abel T (2012) The impact of sleep deprivation on neuronal and glial signaling pathways important for memory and synaptic plasticity. Cell Signal 24:1251–1260

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Hu LF, Lu M, Hon Wong PT, Bian JS (2011) Hydrogen sulfide: neurophysiology and neuropathology. Antioxid Redox Signal 15:405–419

    CAS  PubMed  Google Scholar 

  7. Qu K, Lee SW, Bian JS, Low CM, Wong PT (2008) Hydrogen sulfide: neurochemistry and neurobiology. Neurochem Int 52:155–165

    CAS  PubMed  Google Scholar 

  8. Tan BH, Wong PT, Bian JS (2010) Hydrogen sulfide: a novel signaling molecule in the central nervous system. Neurochem Int 56:3–10

    CAS  PubMed  Google Scholar 

  9. Kumar M, Modi M, Sandhir R (2017) Hydrogen sulfide attenuates homocysteine-induced cognitive deficits and neurochemical alterations by improving endogenous hydrogen sulfide levels. BioFactors 43:434–450

    CAS  PubMed  Google Scholar 

  10. Kimura H (2013) Physiological role of hydrogen sulfide and polysulfide in the central nervous system. Neurochem Int 63:492–497

    CAS  PubMed  Google Scholar 

  11. Liu C, Xu X, Gao J, Zhang T, Yang Z (2016) Hydrogen sulfide prevents synaptic plasticity from VD-induced damage via Akt/GSK-3beta pathway and notch signaling pathway in rats. Mol Neurobiol 53:4159–4172

    CAS  PubMed  Google Scholar 

  12. Shefa U, Kim D, Kim MS, Jeong NY, Jung J (2018) Roles of gasotransmitters in synaptic plasticity and neuropsychiatric conditions. Neural Plast 2018:1824713

    PubMed  PubMed Central  Google Scholar 

  13. He JT, Li H, Yang L, Mao CY (2019) Role of hydrogen sulfide in cognitive deficits: evidences and mechanisms. Eur J Pharmacol 849:146–153

    CAS  PubMed  Google Scholar 

  14. Duan H, Li L, Shen S, Ma Y, Yin X, Liu Z, Yuan C, Wang Y, Zhang J (2020) Hydrogen sulfide reduces cognitive impairment in rats after subarachnoid hemorrhage by ameliorating neuroinflammation mediated by the TLR4/NF-kappaB pathway in microglia. Front Cell Neurosci 14:210

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Vandini E, Ottani A, Zaffe D, Calevro A, Canalini F, Cavallini GM, Rossi R, Guarini S, Giuliani D (2019) Mechanisms of hydrogen sulfide against the progression of severe Alzheimer’s disease in transgenic mice at different ages. Pharmacology 103:50–60

    CAS  PubMed  Google Scholar 

  16. Zhang LM, Jiang CX, Liu DW (2009) Hydrogen sulfide attenuates neuronal injury induced by vascular dementia via inhibiting apoptosis in rats. Neurochem Res 34:1984–1992

    CAS  PubMed  Google Scholar 

  17. Zou W, Yuan J, Tang ZJ, Wei HJ, Zhu WW, Zhang P, Gu HF, Wang CY, Tang XQ (2017) Hydrogen sulfide ameliorates cognitive dysfunction in streptozotocin-induced diabetic rats: involving suppression in hippocampal endoplasmic reticulum stress. Oncotarget 8:64203–64216

    PubMed  PubMed Central  Google Scholar 

  18. Yuan DS, Huang YQ, Fu YJ, Xie J, Huang YL, Zhou SS, Sun PY, Tang XQ (2020) Hydrogen sulfide alleviates cognitive deficiency and hepatic dysfunction in a mouse model of acute liver failure. Exp Ther Med 20:671–677

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Li X, Zhuang YY, Wu L, Xie M, Gu HF, Wang B, Tang XQ (2020) Hydrogen sulfide ameliorates cognitive dysfunction in formaldehyde-exposed rats: involvement in the upregulation of brain-derived neurotrophic factor. Neuropsychobiology 79:119–130

    CAS  PubMed  Google Scholar 

  20. Mizushima N, Komatsu M (2011) Autophagy: renovation of cells and tissues. Cell 147:728–741

    CAS  PubMed  Google Scholar 

  21. Ghavami S, Shojaei S, Yeganeh B, Ande SR, Jangamreddy JR, Mehrpour M, Christoffersson J, Chaabane W, Moghadam AR, Kashani HH, Hashemi M, Owji AA, Los MJ (2014) Autophagy and apoptosis dysfunction in neurodegenerative disorders. Prog Neurobiol 112:24–49

    CAS  PubMed  Google Scholar 

  22. 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 10:53

    PubMed  PubMed Central  Google Scholar 

  23. Cao Y, Li Q, Liu L, Wu H, Huang F, Wang C, Lan Y, Zheng F, Xing F, Zhou Q, Li Q, Shi H, Zhang B, Wang Z, Wu X (2019) Modafinil protects hippocampal neurons by suppressing excessive autophagy and apoptosis in mice with sleep deprivation. Br J Pharmacol 176:1282–1297

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Shui M, Liu X, Zhu Y, Wang Y (2016) Exogenous hydrogen sulfide attenuates cerebral ischemia-reperfusion injury by inhibiting autophagy in mice. Can J Physiol Pharmacol 94:1187–1192

    CAS  PubMed  Google Scholar 

  25. Jiang WW, Huang BS, Han Y, Deng LH, Wu LX (2017) Sodium hydrosulfide attenuates cerebral ischemia/reperfusion injury by suppressing overactivated autophagy in rats. FEBS Open Bio 7:1686–1695

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Michan S, Sinclair D (2007) Sirtuins in mammals: insights into their biological function. Biochem J 404:1–13

    CAS  PubMed  Google Scholar 

  27. Cao Y, Yan Z, Zhou T, Wang G (2017) SIRT1 regulates cognitive performance and ability of learning and memory in diabetic and nondiabetic models. J Diabetes Res 2017:7121827

    PubMed  PubMed Central  Google Scholar 

  28. Lu Y, Tan L, Wang X (2019) Circular HDAC9/microRNA-138/Sirtuin-1 pathway mediates synaptic and amyloid precursor protein processing deficits in Alzheimer’s disease. Neurosci Bull 35:877–888

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Michan S, Li Y, Chou MM, Parrella E, Ge H, Long JM, Allard JS, Lewis K, Miller M, Xu W, Mervis RF, Chen J, Guerin KI, Smith LE, McBurney MW, Sinclair DA, Baudry M, de Cabo R, Longo VD (2010) SIRT1 is essential for normal cognitive function and synaptic plasticity. J Neurosci 30:9695–9707

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Gomes BAQ, Silva JPB, Romeiro CFR, Dos Santos SM, Rodrigues CA, Goncalves PR, Sakai JT, Mendes PFS, Varela ELP, Monteiro MC (2018) Neuroprotective mechanisms of resveratrol in Alzheimer’s disease: role of SIRT1. Oxid Med Cell Longev 2018:8152373

    PubMed  PubMed Central  Google Scholar 

  31. Jiang Y, Botchway BOA, Hu Z, Fang M (2019) Overexpression of SIRT1 inhibits corticosterone-induced autophagy. Neuroscience 411:11–22

    CAS  PubMed  Google Scholar 

  32. Zuo JX, Li M, Jiang L, Lan F, Tang YY, Kang X, Zou W, Wang CY, Zhang P, Tang XQ (2020) Hydrogen sulfide prevents sleep deprivation-induced hippocampal damage by upregulation of Sirt1 in the hippocampus. Front Neurosci 14:169

    PubMed  PubMed Central  Google Scholar 

  33. Wen X, Qi D, Sun Y, Huang X, Zhang F, Wu J, Fu Y, Ma K, Du Y, Dong H, Liu Y, Liu H, Song Y (2014) H(2)S attenuates cognitive deficits through Akt1/JNK3 signaling pathway in ischemic stroke. Behav Brain Res 269:6–14

    CAS  PubMed  Google Scholar 

  34. Tang YY, Wang AP, Wei HJ, Li MH, Zou W, Li X, Wang CY, Zhang P, Tang XQ (2018) Role of silent information regulator 1 in the protective effect of hydrogen sulfide on homocysteine-induced cognitive dysfunction: involving reduction of hippocampal ER stress. Behav Brain Res 342:35–42

    CAS  PubMed  Google Scholar 

  35. Qian C, Jin J, Chen J, Li J, Yu X, Mo H, Chen G (2017) SIRT1 activation by resveratrol reduces brain edema and neuronal apoptosis in an experimental rat subarachnoid hemorrhage model. Mol Med Rep 16:9627–9635

    CAS  PubMed  Google Scholar 

  36. Suchecki D, Duarte Palma B, Tufik S (2000) Sleep rebound in animals deprived of paradoxical sleep by the modified multiple platform method. Brain Res 875:14–22

    CAS  PubMed  Google Scholar 

  37. Suchecki D, Tufik S (2000) Social stability attenuates the stress in the modified multiple platform method for paradoxical sleep deprivation in the rat. Physiol Behav 68:309–316

    CAS  PubMed  Google Scholar 

  38. Li XN, Chen L, Luo B, Li X, Wang CY, Zou W, Zhang P, You Y, Tang XQ (2017) Hydrogen sulfide attenuates chronic restrain stress-induced cognitive impairment by upreglulation of Sirt1 in hippocampus. Oncotarget 8:100396–100410

    PubMed  PubMed Central  Google Scholar 

  39. Lueptow LM (2017) Novel object recognition test for the investigation of learning and memory in mice. J Vis Exp. https://doi.org/10.3791/55718

    Article  PubMed  PubMed Central  Google Scholar 

  40. Wang S, Su G, Zhang Q, Zhao T, Liu Y, Zheng L, Zhao M (2018) Walnut ( Juglans regia) peptides reverse sleep deprivation-induced memory impairment in rat via alleviating oxidative Stress. J Agric Food Chem 66:10617–10627

    CAS  PubMed  Google Scholar 

  41. Trost Bobic T, Secic A, Zavoreo I, Matijevic V, Filipovic B, Kolak Z, Basic Kes V, Ciliga D, Sajkovic D (2016) The impact of sleep deprivation on the brain. Acta Clin Croat 55:469–473

    PubMed  Google Scholar 

  42. Pothuizen HH, Zhang WN, Jongen-Relo AL, Feldon J, Yee BK (2004) Dissociation of function between the dorsal and the ventral hippocampus in spatial learning abilities of the rat: a within-subject, within-task comparison of reference and working spatial memory. Eur J Neurosci 19:705–712

    PubMed  Google Scholar 

  43. Shih YH, Tsai SF, Huang SH, Chiang YT, Hughes MW, Wu SY, Lee CW, Yang TT, Kuo YM (2016) Hypertension impairs hippocampus-related adult neurogenesis, CA1 neuron dendritic arborization and long-term memory. Neuroscience 322:346–357

    CAS  PubMed  Google Scholar 

  44. Ott CV, Johnson CB, Macoveanu J, Miskowiak K (2019) Structural changes in the hippocampus as a biomarker for cognitive improvements in neuropsychiatric disorders: a systematic review. Eur Neuropsychopharmacol 29:319–329

    CAS  PubMed  Google Scholar 

  45. Alzoubi KH, Mayyas F, Abu Zamzam HI (2019) Omega-3 fatty acids protects against chronic sleep-deprivation induced memory impairment. Life Sci 227:1–7

    CAS  PubMed  Google Scholar 

  46. Li H, Yu F, Sun X, Xu L, Miu J, Xiao P (2019) Dihydromyricetin ameliorates memory impairment induced by acute sleep deprivation. Eur J Pharmacol 853:220–228

    CAS  PubMed  Google Scholar 

  47. Manchanda S, Singh H, Kaur T, Kaur G (2018) Low-grade neuroinflammation due to chronic sleep deprivation results in anxiety and learning and memory impairments. Mol Cell Biochem 449:63–72

    CAS  PubMed  Google Scholar 

  48. Ocalan B, Cakir A, Koc C, Suyen GG, Kahveci N (2019) Uridine treatment prevents REM sleep deprivation-induced learning and memory impairment. Neurosci Res 148:42–48

    CAS  PubMed  Google Scholar 

  49. Bredesen DE, Rao RV, Mehlen P (2006) Cell death in the nervous system. Nature 443:796–802

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Xu Y, Tian Y, Tian Y, Li X, Zhao P (2016) Autophagy activation involved in hypoxic-ischemic brain injury induces cognitive and memory impairment in neonatal rats. J Neurochem 139:795–805

    CAS  PubMed  Google Scholar 

  51. Hao Y, Li W, Wang H, Zhang J, Yu C, Tan S, Wang H, Xu X, Dong J, Yao B, Zhou H, Zhao L, Peng R (2018) Autophagy mediates the degradation of synaptic vesicles: a potential mechanism of synaptic plasticity injury induced by microwave exposure in rats. Physiol Behav 188:119–127

    CAS  PubMed  Google Scholar 

  52. Li X, Wu Z, Zhang Y, Xu Y, Han G, Zhao P (2017) Activation of autophagy contributes to sevoflurane-induced neurotoxicity in fetal rats. Front Mol Neurosci 10:432

    PubMed  PubMed Central  Google Scholar 

  53. Fusco S, Maulucci G, Pani G (2012) Sirt1: def-eating senescence? Cell Cycle 11:4135–4146

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Shen J, Li Y, Qu C, Xu L, Sun H, Zhang J (2019) The enriched environment ameliorates chronic unpredictable mild stress-induced depressive-like behaviors and cognitive impairment by activating the SIRT1/miR-134 signaling pathway in hippocampus. J Affect Disord 248:81–90

    CAS  PubMed  Google Scholar 

  55. Shen J, Xu L, Qu C, Sun H, Zhang J (2018) Resveratrol prevents cognitive deficits induced by chronic unpredictable mild stress: Sirt1/miR-134 signalling pathway regulates CREB/BDNF expression in hippocampus in vivo and in vitro. Behav Brain Res 349:1–7

    CAS  PubMed  Google Scholar 

  56. Yan WJ, Wang DB, Ren DQ, Wang LK, Hu ZY, Ma YB, Huang JW, Ding SL (2019) AMPKalpha1 overexpression improves postoperative cognitive dysfunction in aged rats through AMPK-Sirt1 and autophagy signaling. J Cell Biochem:doi. https://doi.org/10.1002/jcb.28443

    Article  Google Scholar 

  57. Liu SY, Li D, Zeng HY, Kan LY, Zou W, Zhang P, Gu HF, Tang XQ (2017) Hydrogen sulfide inhibits chronic unpredictable mild stress-induced depressive-like behavior by upregulation of Sirt-1: involvement in suppression of hippocampal endoplasmic reticulum stress. Int J Neuropsychopharmacol 20:867–876

    CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work was supported by National Natural Science Foundation of China (81771178), Natural Science Foundation of Hunan province (2019JJ80101), and the Major Research Topics of the Health Commission of Hunan province (20201911).

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Gao, S., Tang, YY., Jiang, L. et al. H2S Attenuates Sleep Deprivation-Induced Cognitive Impairment by Reducing Excessive Autophagy via Hippocampal Sirt-1 in WISTAR RATS. Neurochem Res 46, 1941–1952 (2021). https://doi.org/10.1007/s11064-021-03314-0

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