Volume 2, Issue 6, November 2016, Page: 101-106
Translocator Protein 18 kDa Involved in the Cognitive Impairment Induced by Isoflurane Inhalation Anesthesia
Rui Zhang, Department of Anesthesiology, Weifang Medical University, Weifang, China
Shanshan Zou, Department of Anesthesiology, Weifang Medical University, Weifang, China
Lingzhong Meng, Department of Anesthesiology, Yale University Medical School, USA
Ming Ding, Department of Anesthesiology, No.89 Hospital of People’s Liberation Army, Weifang, China
Huirong Han, Department of Anesthesiology, Weifang Medical University, Weifang, China
Received: Aug. 23, 2016;       Accepted: Sep. 6, 2016;       Published: Oct. 14, 2016
DOI: 10.11648/j.ijcems.20160206.11      View  3019      Downloads  75
Abstract
Background. Translocator protein 18 kDa (TSPO) plays a key role both in microglial activation and neuroinflammation. Postoperative cognitive decline (POCD), a notable hazard to both patients and society, maybe contribute to deficiently controlled neuroinflammatory processes initiated by anesthesia and surgery. So far it is unclear that whether TSPO is involved in the pathogenesis of POCD or not. Materials and Methods. Twelve adult rats and twelve aged rats were divided into control and isoflurane groups respectively. POCD was induced by a 4-hour exposure of 2% isoflurane. The memory retention capability was assessed by the Morris water maze trial, the mRNA and the protein expression of both TSPO and Iba1 were assessed by real-time quantitative PCR and Western Blot analysis separately. Results. Compared to the control group, the latency time to find platform was longer in the groups exposed to isoflurane (p<0.05); the mRNA and the protein expression of both TSPO and Iba1 were correspondingly upregulated (p<0.05); especially that the severity of cognitive decline and the degree of TSPO and Iba1 over-expression were significantly different between the adult and aged rats (p<0.05); The twice times across the platform showed no significant difference among all the groups. Conclusions. Our study for the first time showed that TSPO may be involved in the pathogenesis of the cognitive decline induced by isoflurane anesthesia. Its role for being a biomarker and an interventional target of POCD deserves future investigation.
Keywords
Postoperative Cognitive Decline (POCD), Translocator Protein 18 kDa (TSPO), Neuroinflammation
To cite this article
Rui Zhang, Shanshan Zou, Lingzhong Meng, Ming Ding, Huirong Han, Translocator Protein 18 kDa Involved in the Cognitive Impairment Induced by Isoflurane Inhalation Anesthesia, International Journal of Clinical and Experimental Medical Sciences. Vol. 2, No. 6, 2016, pp. 101-106. doi: 10.11648/j.ijcems.20160206.11
Copyright
Copyright © 2016 Authors retain the copyright of this article.
This article is an open access article distributed under the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Reference
[1]
Papadopoulos V, Baraldi M, Guilarte TR, et al. Translocator protein (18kDa): new nomenclature for the peripheral-type benzodiazepine receptor based on its structure and molecular function. Trends Pharmacol Sci. 2006;27:402-409. doi: 10.1016/j.tips.2006.06.005
[2]
Casellas P, Galiegue S, Basilen AS. Peripheral benzodiazepine receptors and mitochondrial function. Neurochem. Int. 2002; 40: 475–486. doi: http://dx.doi.org/ 10.1016/S0197-0186(01)00118-8.
[3]
Kuhlmann AC, Guilarte TR. Cellular and subcellular localization of peripheral benzodiazepine receptors after trimethyltin neurotoxicity. J Neurochem. 2000;74:1694–1704. doi: 10.1046/j.1471-4159.2000.0741694.x.
[4]
Trapani A, Palazzo C, de Candia M, Lasorsa FM, Trapani G. Targeting of the translocator protein 18 kDa (TSPO): a valuable approach for nuclear and optical imaging of activated microglia. Bioconjug Chem. 2013;24:1415-1428. doi: 10.1021/bc300666f.
[5]
Chauveau F, Boutin H, Van Camp N, Dolle F, Tavitian B. Nuclear imaging of neuroinflammation: a comprehensive review of [11C] PK11195 challengers. Eur J Nucl Med Mol Imaging. 2008; 35: 2304–2319. doi: 10.1007/s00259-008-0908-9.
[6]
Seymour DG, Severn AM. Cognitive dysfunction after surgery and anaesthesia: what can we tell the grandparents? Age Ageing. 2009;38:147-150. doi: 10.1093/ageing/afn289.
[7]
Moller JT, Cluitmans P, Rasmussen LS, et al. Long-term postoperative cognitive dysfunction in the elderly ISPOCD1 study. ISPOCD investigators. International Study of Post-Operative Cognitive Dysfunction. Lancet.1998;351:857–861. doi: http://dx.doi.org/10.1016/S0140-6736(97)07382-0.
[8]
Cibelli M, Fidalgo AR, Terrando N, et al. Role of interleukin-1beta in postoperative cognitive dysfunction. Ann Neurol. 2010; 68:360-368. doi: 10.1002/ana.22082.
[9]
Wang Y, He H, Li D, et al. The role of the TLR4 signaling pathway in cognitive deficits following surgery in aged rats. Mol Med Rep. 2013; 7: 1137-1142. doi: 10.3892/mmr.2013.1322.
[10]
Peng L, Xu L, Ouyang W. Role of peripheral inflammatory markers in postoperative cognitive dysfunction (POCD): a meta-analysis. PLoSOne. 2013; 8: e79624. doi: http://dx.doi.org/10.1371/journal.pone.0079624.
[11]
Jiang P, Ling Q, Liu H, Tu W. Intracisternal administration of an interleukin-6 receptor antagonist attenuates surgery-induced cognitive impairment by inhibition of neuroinflammatory responses in aged rats. Exp Ther Med. 2015; 9:982-986. doi: 10.3892/etm.2014.2149.
[12]
Liang G, Ward C, Peng J, Zhao Y, Huang B, Wei H. Isoflurane causes greater neurodegeneration than an equivalent exposure of sevoflurane in the developing brain of neonatal mice. Anesthesiology. 2010; 112: 1325-1334. doi: 10.1097/ALN.0b013e3181d94da5.
[13]
Xie Z, Culley DJ, Dong Y, et al. The commonbinhalation anesthetic isoflurane induces caspase activation and increases amyloid β-protein level in vivo. Ann Neurol. 2008;64:618-627. doi: 10.1002/ana.21548.
[14]
Wu X, Lu Y, Dong Y, et al. The inhalation anesthetic isoflurane increases levels of proinflammatory TNF-α, IL-6, and IL-1β. Neurobiol Aging. 2012; 33: 1364-1378. doi: 10.1016/j.neurobiolaging.2010.11.002.
[15]
Rothhammer V, Mascanfroni ID, Bunse L, et al. Type I interferons and microbial metabolites of tryptophan modulate astrocyte activity and central nervous system inflammation via the aryl hydrocarbon receptor. Nat Med. 2016; 22:586-597. doi: 10.1038/nm.4106.
[16]
Futatsugi A, Kato K, Ogura H, et al. Facilitation of NMDAR-independent LTP and spatial learning in mutant mice lacking ryanodine receptor type 3. Method Neuron. 1999;24:701-713. doi: http://dx.doi.org/10.1016/S0896-6273(00)81123-X.
[17]
Beck KD, Lamballe F, Klein R, et al. Induction of noncatalytic TrkB neurotrophin receptors during axonal sprouting in the adult hippocampus. J Neurosci. 1993;13:4001-4014. Available from: http://www.jneurosci.org/content/13/9/4001.long
[18]
Livak KJ, Schmittgen TD. Analysis of relative gene ex-pression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001; 25: 402-408. doi: 10.1006/meth.2001.1262.
[19]
Li ZQ, Li LX, Mo N, et al. Duration-dependent regulation of autophagy by isoflurane exposure in aged rats. Neurosci Bull. 2015;31:505-513. doi: 10.1007/s12264-015-1549-1.
[20]
Ling YZ, MA W, Yu L, Zhang Y, Liang QS. Decreased PSD95 expression in medial prefrontal cortex (mPFC) was associated with cognitive impairment induced by sevoflurane anesthesia. J Zhejiang Univ Sci B. 2015;16:763-771. doi: 10.1631/jzus. B1500006.
[21]
Ito D, Imai Y, Ohsawa K, Nakajima K, Fukuuchi Y, Kohsaka S. Microglia-specific localisation of a novel calcium binding protein, Iba1. Brain Res Mo Brain Res. 1998;57:1–9. doi: http://dx.doi.org/10.1016/S0169-328X(98)00040-0.
[22]
Wang HL, Ma RH, Fang H, Xue ZG, Liao QW. Impaired Spatial Learning Memory after Isoflurane Anesthesia or Appendectomy in Aged Mice is Associated with Microglia Activation. J Cell Death. 2015;8:9-19. doi: 10.4137/JCD.S30596.
[23]
Hanisch UK, Kettenmann H. Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat Neurosci. 2007; 10: 1387–1394. doi: 10.1038/nn1997.
[24]
Degos V1, Vacas S, Han Z, et al. Depletion of bone marrow-derived macrophages perturbs the innate immune response to surgery and reduces postoperative memory dysfunction. Anesthesiology. 2013; 118: 527-536. doi: 10.1097/ALN.0b013e3182834d94.
[25]
Wu X, Lu Y, Dong Y, et al. The inhalation anesthetic isoflurane increases levels of proinflammatory TNF-α, IL-6, and IL-1β. Neurobiol Aging. 2012; 33: 1364-1378. doi: 10.1016/j.neurobiolaging.2010.11.002.
[26]
Li J, Zhang Z, Lv L, Qiao H, Chen X, Zou C. A bispecific antibody (ScBsAbAgn-2/TSPO) target for Ang-2 and TSPO resulted in therapeutic effects against glioblastomas. Biochem Biophys Res Commun. 2016; 472: 384-391. doi: 10.1016/j.bbrc.2016.02.035.
Browse journals by subject