Abstract
As one of the commonly used inhalation anesthetics in clinical practice, sevoflurane is currently widely applied in surgery for children and the elderly due to its safety and efficacy. However, the neurotoxicity and cognitive impairment induced by sevoflurane exposure cannot be ignored. A recombinant adenovirus with green fluorescent protein-labeled heat shock protein 70 (Hsp70) was constructed and used to infect neural stem cells (NSCs) separated from neonatal mice. Quantitative real-time PCR and Western blot assays were used to evaluate the expression of certain genes. 5‑Ethynyl‑2′‑deoxyuridine staining and cell counting kit assay were used to detect the proliferation and differentiation ability of NSCs. The Morris water maze experiment was used to test the cognitive abilities of mice. Adv-Hsp70 induced the overexpression of Hsp70 in mouse NSCs. Upregulation of Hsp70 promoted the proliferation ability and differentiation of mouse NSCs. NSCs that overexpressed Hsp70 attenuated sevoflurane-induced neurotoxicity and protected cognitive dysfunction in mice under sevoflurane exposure. In summary, our findings demonstrate the potential of overexpression of Hsp70 in NSCs against sevoflurane-induced impairments.
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References
Bhattarai P, Cosacak MI, Mashkaryan V et al (2020) Neuron-glia interaction through Serotonin-BDNF-NGFR axis enables regenerative neurogenesis in Alzheimer’s model of adult zebrafish brain. PLoS Biol 18:e3000585. https://doi.org/10.1371/journal.pbio.3000585
Bobkova NV, Evgen’ev M, Garbuz DG et al (2015) Exogenous Hsp70 delays senescence and improves cognitive function in aging mice. Proc Natl Acad Sci USA 112:16006–16011. https://doi.org/10.1073/pnas.1516131112
Boese AC, Le QE, Pham D, Hamblin MH, Lee JP (2018) Neural stem cell therapy for subacute and chronic ischemic stroke. Stem Cell Res Ther 9:154. https://doi.org/10.1186/s13287-018-0913-2
Boysen M, Kityk R, Mayer MP (2019) Hsp70- and Hsp90-mediated regulation of the conformation of p53 DNA binding domain and p53 cancer variants. Mol Cell 74(831–843):e834. https://doi.org/10.1016/j.molcel.2019.03.032
Chai D, Cheng Y, Jiang H (2019) Fundamentals of fetal toxicity relevant to sevoflurane exposures during pregnancy. Int J Dev Neurosci 72:31–35. https://doi.org/10.1016/j.ijdevneu.2018.11.001
Chen W, Liu N, Shen S et al (2021) Fetal growth restriction impairs hippocampal neurogenesis and cognition via Tet1 in offspring. Cell Rep 37:109912. https://doi.org/10.1016/j.celrep.2021.109912
De Gioia R, Biella F, Citterio G et al (2020) Neural stem cell transplantation for neurodegenerative diseases. Int J Mol Sci. https://doi.org/10.3390/ijms21093103
Fernandez-Fernandez MR, Valpuesta JM (2018) Hsp70 chaperone: a master player in protein homeostasis. F1000Res. https://doi.org/10.12688/f1000research.15528.1
Jiao Y, Fan H, Wang K, Lu S (2019) Sevoflurane impairs short-term memory by affecting PSD-95 and AMPA receptor in the hippocampus of a mouse model. Behav Neurol 2019:1068260. https://doi.org/10.1155/2019/1068260
Ju LS, Yang JJ, Xu N et al (2019) Intergenerational effects of sevoflurane in young adult rats. Anesthesiology 131:1092–1109. https://doi.org/10.1097/ALN.0000000000002920
Khandia R, Munjal AK, Iqbal HMN, Dhama K (2017) Heat shock proteins: therapeutic perspectives in inflammatory disorders. Recent Pat Inflamm Allergy Drug Discov 10:94–104. https://doi.org/10.2174/1872213X10666161213163301
Kong F, Wang H, Guo J et al (2016) Hsp70 suppresses apoptosis of BRL cells by regulating the expression of Bcl-2, cytochrome C, and caspase 8/3. In Vitro Cell Dev Biol Anim 52:568–575. https://doi.org/10.1007/s11626-016-0005-5
Koutsogiannaki S, Hou L, Babazada H et al (2019) The volatile anesthetic sevoflurane reduces neutrophil apoptosis via Fas death domain-Fas-associated death domain interaction. FASEB J 33:12668–12679. https://doi.org/10.1096/fj.201901360R
Lazutkin A, Podgorny O, Enikolopov G (2019) Modes of division and differentiation of neural stem cells. Behav Brain Res 374:112118. https://doi.org/10.1016/j.bbr.2019.112118
Li H, Yang J, Wang Y, Liu Q, Cheng J, Wang F (2019) Neuroprotective effects of increasing levels of HSP70 against neuroinflammation in Parkinson’s disease model by inhibition of NF-kappaB and STAT3. Life Sci 234:116747. https://doi.org/10.1016/j.lfs.2019.116747
Li H, Yu Z, Zhang W (2020) Misfolded protein aggregation and altered cellular pathways in neurodegenerative diseases. Stemedicine 1:e63. https://doi.org/10.37175/stemedicine.v1i4.63
Lu Z, Sun J, Xin Y, Chen K, Ding W, Wang Y (2018) Sevoflurane-induced memory impairment in the postnatal developing mouse brain. Exp Ther Med 15:4097–4104. https://doi.org/10.3892/etm.2018.5950
Mayer MP (2013) Hsp70 chaperone dynamics and molecular mechanism. Trends Biochem Sci 38:507–514. https://doi.org/10.1016/j.tibs.2013.08.001
Mayer MP, Gierasch LM (2019) Recent advances in the structural and mechanistic aspects of Hsp70 molecular chaperones. J Biol Chem 294:2085–2097. https://doi.org/10.1074/jbc.REV118.002810
Mayer MP, Gierasch LM (2020) Correction: recent advances in the structural and mechanistic aspects of Hsp70 molecular chaperones. J Biol Chem 295:288. https://doi.org/10.1074/jbc.AAC119.012167
Muranova LK, Ryzhavskaya AS, Sudnitsyna MV, Shatov VM, Gusev NB (2019) Small heat shock proteins and human neurodegenerative diseases. Biochemistry (mosc) 84:1256–1267. https://doi.org/10.1134/S000629791911004X
Palanca BJA, Avidan MS, Mashour GA (2017) Human neural correlates of sevoflurane-induced unconsciousness. Br J Anaesth 119:573–582. https://doi.org/10.1093/bja/aex244
Porto RR, Dutra FD, Crestani AP, Holsinger RMD, Quillfeldt JA, de Homem Bittencourt PI, de Oliveira Alvares L (2018) HSP70 facilitates memory consolidation of fear conditioning through MAPK pathway in the hippocampus. Neuroscience 375:108–118. https://doi.org/10.1016/j.neuroscience.2018.01.028
Roufayel R, Kadry S (2019) Molecular chaperone HSP70 and key regulators of apoptosis—a review. Curr Mol Med 19:315–325. https://doi.org/10.2174/1566524019666190326114720
Saini J, Sharma PK (2018) Clinical, prognostic and therapeutic significance of heat shock proteins in cancer. Curr Drug Targets 19:1478–1490. https://doi.org/10.2174/1389450118666170823121248
Song YJ, Zhong CB, Wang XB (2019) Heat shock protein 70: a promising therapeutic target for myocardial ischemia-reperfusion injury. J Cell Physiol 234:1190–1207. https://doi.org/10.1002/jcp.27110
Suehara T, Morishita J, Ueki M, Ueno M, Maekawa N, Mizobuchi S (2016) Effects of sevoflurane exposure during late pregnancy on brain development of offspring mice. Paediatr Anaesth 26:52–59. https://doi.org/10.1111/pan.12785
Tian R, Guo K, Wu B, Wang H (2020a) Correction to: overexpression of Shrm4 promotes proliferation and differentiation of neural stem cells through activation of GABA signaling pathway. Mol Cell Biochem 472:255–257. https://doi.org/10.1007/s11010-020-03786-8
Tian R, Guo K, Wu B, Wang H (2020b) Overexpression of Shrm4 promotes proliferation and differentiation of neural stem cells through activation of GABA signaling pathway. Mol Cell Biochem 463:115–126. https://doi.org/10.1007/s11010-019-03634-4
Ulrich H, Abbracchio MP, Burnstock G (2012) Extrinsic purinergic regulation of neural stem/progenitor cells: implications for CNS development and repair. Stem Cell Rev Rep 8:755–767. https://doi.org/10.1007/s12015-012-9372-9
Umukoro S, Aluko OM, Eduviere AT, Owoeye O (2016) Evaluation of adaptogenic-like property of methyl jasmonate in mice exposed to unpredictable chronic mild stress. Brain Res Bull 121:105–114. https://doi.org/10.1016/j.brainresbull.2015.11.016
Urban N, Blomfield IM, Guillemot F (2019) Quiescence of adult mammalian neural stem cells: a highly regulated rest. Neuron 104:834–848. https://doi.org/10.1016/j.neuron.2019.09.026
Vitanza NA, Johnson AJ, Wilson AL et al (2021) Locoregional infusion of HER2-specific CAR T cells in children and young adults with recurrent or refractory CNS tumors: an interim analysis. Nat Med 27:1544–1552. https://doi.org/10.1038/s41591-021-01404-8
Wang Y, Yin S, Xue H, Yang Y, Zhang N, Zhao P (2018) Mid-gestational sevoflurane exposure inhibits fetal neural stem cell proliferation and impairs postnatal learning and memory function in a dose-dependent manner. Dev Biol 435:185–197. https://doi.org/10.1016/j.ydbio.2018.01.022
Wang C, Li L, Xu H, Lv H, Zhang H (2019) Effect of desflurane-remifentanil or sevoflurane-remifentanil on early recovery in elderly patients: a meta-analysis of randomized controlled trials. Pharmazie 74:201–205. https://doi.org/10.1691/ph.2019.8935
Wu Z, Li X, Zhang Y, Tong D, Wang L, Zhao P (2018) Effects of sevoflurane exposure during mid-pregnancy on learning and memory in offspring rats: beneficial effects of maternal exercise. Front Cell Neurosci 12:122. https://doi.org/10.3389/fncel.2018.00122
Xu L, Shen J, Yu L, Sun J, McQuillan PM, Hu Z, Yan M (2018) Role of autophagy in sevoflurane-induced neurotoxicity in neonatal rat hippocampal cells. Brain Res Bull 140:291–298. https://doi.org/10.1016/j.brainresbull.2018.05.020
Yang X, Zheng YT, Rong W (2019) Sevoflurane induces apoptosis and inhibits the growth and motility of colon cancer in vitro and in vivo via inactivating Ras/Raf/MEK/ERK signaling. Life Sci 239:116916. https://doi.org/10.1016/j.lfs.2019.116916
Yun CW, Kim HJ, Lim JH, Lee SH (2019) Heat shock proteins: agents of cancer development and therapeutic targets in anti-cancer therapy. Cells. https://doi.org/10.3390/cells9010060
Zhang JJ, Zhu JJ, Hu YB et al (2017) Transplantation of bFGF-expressing neural stem cells promotes cell migration and functional recovery in rat brain after transient ischemic stroke. Oncotarget 8:102067–102077. https://doi.org/10.18632/oncotarget.22155
Zheng H, Dong Y, Xu Z, Crosby G, Culley DJ, Zhang Y, Xie Z (2013) Sevoflurane anesthesia in pregnant mice induces neurotoxicity in fetal and offspring mice. Anesthesiology 118:516–526. https://doi.org/10.1097/ALN.0b013e3182834d5d
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Chen, Y., Xie, Y. & Ni, H. Effects of overexpression of Hsp70 in neural stem cells on neurotoxicity and cognitive dysfunction in neonatal mice under sevoflurane exposure. Exp Brain Res 240, 3207–3216 (2022). https://doi.org/10.1007/s00221-022-06490-9
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DOI: https://doi.org/10.1007/s00221-022-06490-9