eISSN: 1896-9151
ISSN: 1734-1922
Archives of Medical Science
Current issue Archive Manuscripts accepted About the journal Special issues Editorial board Abstracting and indexing Subscription Contact Instructions for authors
SCImago Journal & Country Rank
vol. 14
Experimental research

The effect of celastrol on learning and memory in diabetic rats after sevoflurane inhalation

Wei-Tao Liao, Xiao-Yu Xiao, Yinaxian Zhu, Shao-Peng Zhou

Arch Med Sci 2018; 14, 2: 370–380
Online publish date: 2016/11/18
View full text
Get citation
JabRef, Mendeley
Papers, Reference Manager, RefWorks, Zotero
Introduction: The aim was to devise an animal model showing some of the neuropathological changes seen in senile dementia, and to investigate the effect of celastrol on cognition neuropathology in this model.

Material and methods: Forty male Sprague Dawley rats weighing 300–350 g were randomly divided into 5 groups (n = 8 each): control (Con); inhaled sevoflurane (Sev); diabetes mellitus (DM); diabetes mellitus + inhaled sevoflurane (DM/Sev); diabetes + inhaled sevoflurane + celastrol (Cel). Diabetes was induced by an intraperitoneal injection of streptozotocin (STZ). After 20 days, the Sev, DM/Sev and Cel group rats inhaled 3% sevoflurane for 2 h, while the control and DM groups inhaled air. Cel group rats were given intraperitoneal injections of celastrol (0.7 mg/kg) daily for 4 days, while the control group received intraperitoneal injections of an equal volume of dimethylsulfoxide. The Morris water maze test was performed to test cognition. Animals were killed after the last water maze test and Congo red staining was used to observe deposition of amyloid substance in the hippocampus. The expression of GFAP and IGF-1 in the hippocampus was observed by immunohistochemistry.

Results: Diabetes decreased cognition, increased amyloid substance and GFAP expression, and decreased IGF-1 expression in the hippocampus (all p-values < 0.05). Sevoflurane administration intensified and celastrol decreased these changes (all p-values < 0.05).

Conclusions: Sev/DM rats showed cognitive and neurochemical changes similar to those seen in senile dementia. Celastrol decreased these changes and should be evaluated further as a possible clinical agent in dementia.

diabetic, sevoflurane, celastrol, Morris water maze, hippocampus, GFAP, IGF-1

Marcheezi VT. Alzheimer’s dementia begins as a disease of small blood vessels, damaged by oxidative-induced inflammation and dysregulated amyloid metabolism: implications for early detection and therapy. FASEB J 2011; 25: 5-13.
Zhang M, Luo G, Zhou Y, Wang S, Zhong Z. Phenotypic screens targeting neurodegenerative diseases. J Biomol Screen 2014; 19: 1-16.
Wang KC, Woung LC, Tsai MT, Liu CC, Su YH, Li CY. Risk of Alzheimer’s disease in relation to diabetes: a population-based cohort study. Neuroepidemiology 2012; 38: 237-44.
Wang SQ, Fang F, Xue ZG, Cang J, Zhang XG. Neonatal sevoflurane anesthesia induces long-term memory impairment and decreases hippocampal PSD-95 expression without neuronal loss. Eur Rev Med Pharmacol Sci 2013; 17: 941-50.
Dong Y, Zhang G, Zhang B, et al. The common inhalational anesthetic sevoflurane induces apoptosis and increases beta-amyloid protein levels. Arch Neurol 2009; 66: 620-31.
Allison AC, Cacabelos R, Lombardi VR, Alvarez XA, Vigo C. Celastrol, a potent antioxidant and anti-inflammatory drug, as a possible treatment for Alzheimer’s disease. Prog Neuropsychopharmacol Biol Psychiatry 2001; 25: 1341-57.
Paris D, Ganey NJ, Laporte V, et al. Reduction of beta amyloid pathology by celastrol in a transgenic mouse model of Alzheimer’s disease. J Neuroinflammation 2010; 7: 17.
Westerheide SD, Bosman JD, Mbadugha BNA, et al. Celastrols as inducers of heat shock response and cytoprotection. J Biol Chem 2004; 279: 56053-60.
Nam SM, Yi SS, Yoo DY, et al. Changes in cyclooxygenase-2 immunoreactivity in the hippocampus in a model of streptozotocin-induced type-1 diabetic rats. J Vet Med Sci 2012; 74: 977-82.
Baluchnejadmojarad T, Roghani M. Chronic epogallocatechin 3-gallate learning and memory deficits in diabetic rats via modulation of nitric oxide and oxidative stress. Behav Brain Res 2011; 224: 305-10.
Castilho AF, Liberal JT, Baptista FI, Gaspar JM, Carvalho AL, Ambrosio AF. Elevated glucose concentration changes the content and cellular localization of AMPA receptors in the retina but not in the hippocampus. Neuroscience 2012; 219: 23-32.
Slemmer JE, Chacka IJ, Sweener MI, Weber JT. Antioxidants and free radical scavengers for the treatment of stroke, traumatic brain injury, and aging. Curr Med Chem 2008; 15: 404-14.
Wang WY, Wang H, Luo LJ, et al. The effects of metabatropic glutamate receptor 7 allosteric agonist N-di-benzhydryoethane-1,2-diaminendihydrochloride on developmental sevoflurane neurotoxicity: role of extracellular signal-regulated kinase 1 and 2 mitogen-activated protein kinase signaling pathway. Neuroscience 2012; 205: 167-77.
Peng S, Zhang Y, Sun DP, Zhang DX, Fang Q, Li GJ. The effect of sevoflurane anesthesia on cognitive function and the expression of Insulin-like Growth Factor-1 in CA1 region of hippocampus in old rats. Mol Biol Rep 2011; 38: 1195-9.
Obal D, Preckel B, Scharbatke H, et al. One MAC of sevoflurane provide against reperfusion injury in the heart in vivo. Br J Anaesth 2001; 87: 905-11.
Vorhees CV, Williams MT. Morris water maze: procedures for assessing spatgial and related procedures for assessing spatial and related forms of learning and memory. Nat Protocol 2006; 1: 848-58.
Dhooge R, Deyn PP. Applications of the Morris water maze in the study of learning and memory. Brain Res Rev 2001; 36: 60-9.
Zheng X, Zhou J, Xia Y. The role of TNF-alpha in regulating ketamine-induced hippocampal neurotoxicity. Arch Med Sci 2015; 6: 1296-302.
Jolivalt CG, Hurford R, Lee CA, Durnaop W, Rockenstein E, Masliah E. Type I diabetes exaggerates features of Alzheimer’s disease in APP transgenic mice. Exp Neurol 2010; 223: 422-31.
Hokama M, Oka S, Leon J, et al. Altered expression of diabetes-related genes in Alzheimer’s disease brains: the Hisayama study. Cerebral Cortex 2014; 24: 2476-88.
Steen E, Terry BM, Rivera EJ, et al. Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer’s disease is this type 3 diabetes? J Alzheimer’s Dis 2005; 7: 63-80.
Satomoto M, Satoh Y, Teriu K, et al. Neonatal exposure to sevoflurane induces abnormal social behaviors and deficits in fear conditioning in mice. Anesthesiology 2009; 110: 628-37.
Wong CH, Liu TZ, Chye SM, et al. Sevoflurane-induced oxidative stress and cellular injury in human peripheral polymorphonuclear neutrophils. Food Chem Toxicol 2006; 44: 1399-407.
Le Freche H, Brouillette J, Fernandez-Gomez FJ, et al. Tau phosphorylation sevoflurane anesthesia: an association to postoperative cognitive impairment. Anesthesiology 2012; 116: 779-87.
Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer’s disease progress and problems on the road to therapeutics. Science 2002; 297: 353-6.
Farkas E, Luiten PG, Bari F. Permanent bilateral carotid artery occlusion in the rat: a model for chronic cerebral hypoperfusion-related neurodegenerative disease. Brain Res Rev 2007; 54: 162-80.
Cheng G, Whitehead SM, Hachinski V, Cechetto D. Effects of pyrrolidine dithiocarbamate in beta amyloid (25-35)-induced imflammatory responses and memory deficits in the rat. Neurobiol Dis 2006; 23: 140-51.
Schliebs R, Arendt T. The cholinergic system in aging and neurodegeneration. Behav Brain Res 2011; 221: 555-63.
Nagele RG, Weigel J, Venkataraman V, Imaki H, Wang KC, Weigel J. Contribution of glial cells to the development of amyloid plaques in Alzheimer’s disease. Neurobiol Aging 2004; 25: 663-74.
Koehler RC, Roman RJ, Harder DR. Astrocytes and the regulation of cerebral blood flow. Trends Neurosci 2009; 32: 160-9.
Lopez-Lopez C, Dietrich MO, Metzger F, Loetscher H, Torres-Aleman I. Disturbed cross talk between insulin-like growth factor-I and AMP-activated protein kinase as a possible cause of vascular dysfunction in the amyloid precursor protein/presenilin 2 mouse model of Alzheimer’s disease. J Neurosci 2007; 27: 824-31.
Messier C, Teutenberg K. The role of insulin, insulin growth factor, and insulin-degrading enzyme in brain aging and Alzheimer’s disease. Neural Plast 2005; 12: 311-28.
Bakkar N, Guttridge DC. NFkappaB signaling: a tale of two pathways in skeletal myogenesis. Physiol Rev 2010; 90: 495-511.
Sanz AB, Sanchez-Nino MD, Ramos AM, et al. NF-kappaB in renal inflammation. J Am Soc Nephrol 2010; 21: 1254-62.
Jung HW, Chung YS, Kim YK. Celastrol inhibits production of nitric oxide and pro-inflammatory cytokines through MAPK signal transduction and NF-kappaB in LPS-stimulated BV-2 microglial cells. Exp Molec Med 2007; 6: 715-21.
Zhang X, Zhou J, Xia Y. The role of TNFalpha in regulating ketamine-induced hippocampal neurotoxicity. Arch Med Sci 2015; 11: 1296-302.
Kim JE, Lee MH, Nam DH, et al. Celastrol, an NF-kappaB inhibitor, improves insulin resistance and attenuates renal injury in db/db mice. PLoS One 2013; 8: e62068.
Quick links
© 2019 Termedia Sp. z o.o. All rights reserved.
Developed by Bentus.
PayU - płatności internetowe