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Published in: Metabolic Brain Disease 4/2020

01-04-2020 | Diabetes | Original Article

Curcumin attenuates cytoplasmic/endoplasmic reticulum stress, apoptosis and cholinergic dysfunction in diabetic rat hippocampus

Authors: Walaa A. Keshk, Walaa S. Elseady, Naglaa I. Sarhan, Doaa H. Zineldeen

Published in: Metabolic Brain Disease | Issue 4/2020

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Abstract

Diabetes mellitus (DM) is associated with the increased risk of the central nervous system complications as cerebrovascular disease, impaired cognition, dementia and neurodegeneration. Curcumin is a polyphenol with anti-oxidant, anti-inflammatory, anti-hyperlipidemic, and anti-cancer effects. Therefore, the present study was aimed to focus on the mechanistic insights of diabetes-induced hippocampal neurodegeneration in addition to shedding the light on the modulatory effect of curcumin. Twenty-eight male Wistar rats were randomly divided into four groups. Type I DM was induced by a single intra-peritoneal injection of streptozotocin (STZ) (65 mg/kg b.w.). Curcumin (100 mg/kg b.w.) was given to the diabetic group after the induction and for eight weeks. Hippocampal glucose-regulated protein 78 (GRP78), activating transcription factor 4 (ATF-4), Bcl2 and choline acetyl transferase (ChAT) genes expression were assessed. Heat shock protein 70 (HSP70), Bcl-2-Associated X protein (Bax), Interferon-γ (INF-γ) and CCAAT-enhancer-binding protein homologous protein (CHOP) levels in the hippocampus were immunoassayed, in addition to the assessment of glycemic and redox status. Curcumin significantly improved blood glucose level, redox status, cellular stress, and decreased INF-γ and Bax levels, down-regulated GRP78 and ATF-4 expression, meanwhile, up-regulated Bcl2 and ChAT expression in hippocampus. Histological findings proved the biochemical and molecular findings. Our results support curcumin as a potential neuro-protective agent against diabetes induced hippocampal neurodegeneration.
Literature
go back to reference Bancroft J. D, Layton C and Suvarna S. K. (2013) Bancroft's theory and practice of histological Techniques8th edition. 7th edition, ed. Oxford: Churchill Livingstone: Elsevier Bancroft J. D, Layton C and Suvarna S. K. (2013) Bancroft's theory and practice of histological Techniques8th edition. 7th edition, ed. Oxford: Churchill Livingstone: Elsevier
go back to reference Chang CC, Chen SD, Lin TK, Chang WN, Liou CW, Chang AY, Chan SH, Chuang YC (2014) Heat shock protein 70 protects against seizure-induced neuronal cell death in the hippocampus following experimental status epilepticus via inhibition of nuclear factor-κB activation-induced nitric oxide synthase II expression. Neurobiol Dis 62:241–249. https://doi.org/10.1016/j.nbd.2013.10.012 CrossRefPubMed Chang CC, Chen SD, Lin TK, Chang WN, Liou CW, Chang AY, Chan SH, Chuang YC (2014) Heat shock protein 70 protects against seizure-induced neuronal cell death in the hippocampus following experimental status epilepticus via inhibition of nuclear factor-κB activation-induced nitric oxide synthase II expression. Neurobiol Dis 62:241–249. https://​doi.​org/​10.​1016/​j.​nbd.​2013.​10.​012 CrossRefPubMed
go back to reference Huang HC, Zheng BW, Guo Y, Zhao J, Zhao JY, Ma XW, Jiang ZF (2016) Antioxidative and Neuroprotective effects of Curcumin in an Alzheimer's disease rat model co-treated with Intracerebroventricular Streptozotocin and subcutaneous D-Galactose. J Alzheimers Dis 52(3):899–911. https://doi.org/10.3233/JAD-150872 CrossRefPubMed Huang HC, Zheng BW, Guo Y, Zhao J, Zhao JY, Ma XW, Jiang ZF (2016) Antioxidative and Neuroprotective effects of Curcumin in an Alzheimer's disease rat model co-treated with Intracerebroventricular Streptozotocin and subcutaneous D-Galactose. J Alzheimers Dis 52(3):899–911. https://​doi.​org/​10.​3233/​JAD-150872 CrossRefPubMed
go back to reference Kanitkar M, Bhonde RR (2008) Curcumin treatment enhances islet recovery by induction of heat shock response proteins, Hsp70 and heme oxygenase-1, during cryopreservation. Life Sci 82(3–4):182–189CrossRefPubMed Kanitkar M, Bhonde RR (2008) Curcumin treatment enhances islet recovery by induction of heat shock response proteins, Hsp70 and heme oxygenase-1, during cryopreservation. Life Sci 82(3–4):182–189CrossRefPubMed
go back to reference Kim HY, Park EJ, Joe EH, Jou I (2003) Curcumin suppresses Janus kinase-STAT inflammatory signaling through activation of Src homology 2 domain-containing tyrosine phosphatase 2 in brain microglia. J Immunol 171(11):6072–6079CrossRefPubMed Kim HY, Park EJ, Joe EH, Jou I (2003) Curcumin suppresses Janus kinase-STAT inflammatory signaling through activation of Src homology 2 domain-containing tyrosine phosphatase 2 in brain microglia. J Immunol 171(11):6072–6079CrossRefPubMed
go back to reference Levine RL, Garland D, Oliver CN, Amici A, Climent I, Lenz AG, Ahn BW, Shaltiel S, Stadtman ER (1990) Determination of carbonyl content in oxidatively modified proteins. Methods of Enzymology 186:464–478CrossRef Levine RL, Garland D, Oliver CN, Amici A, Climent I, Lenz AG, Ahn BW, Shaltiel S, Stadtman ER (1990) Determination of carbonyl content in oxidatively modified proteins. Methods of Enzymology 186:464–478CrossRef
go back to reference Lin W, Kemper A, Dupree JL, Harding HP, Ron D, Popko B (2006) Interferon-gamma inhibits central nervous system remyelination through a process modulated by endoplasmic reticulum stress. Brain 129(Pt 5):1306–1318CrossRefPubMed Lin W, Kemper A, Dupree JL, Harding HP, Ron D, Popko B (2006) Interferon-gamma inhibits central nervous system remyelination through a process modulated by endoplasmic reticulum stress. Brain 129(Pt 5):1306–1318CrossRefPubMed
go back to reference Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193(1):265–275PubMed Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193(1):265–275PubMed
go back to reference Luo F, Huang R, Yang YJ, Yu XH (2003) Protective effect and mechanism of pretreatment with curcumin on infectious brain edema in rats. Zhonghua Er Ke Za Zhi 41(12):940–944PubMed Luo F, Huang R, Yang YJ, Yu XH (2003) Protective effect and mechanism of pretreatment with curcumin on infectious brain edema in rats. Zhonghua Er Ke Za Zhi 41(12):940–944PubMed
go back to reference Ron D, Walter P (2007) Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol 8(7):519–529CrossRefPubMed Ron D, Walter P (2007) Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol 8(7):519–529CrossRefPubMed
go back to reference Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, Preibisch S, Rueden C, Saalfeld S, Schmid B, Tinevez J, White D, Hartenstein V, Eliceiri K, Tomancak P, Cardona A (2012) Fiji: an open-source platform for biological-image analysis. Nat Methods 9(7):676–682. https://doi.org/10.1038/nmeth.2019 CrossRefPubMed Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, Preibisch S, Rueden C, Saalfeld S, Schmid B, Tinevez J, White D, Hartenstein V, Eliceiri K, Tomancak P, Cardona A (2012) Fiji: an open-source platform for biological-image analysis. Nat Methods 9(7):676–682. https://​doi.​org/​10.​1038/​nmeth.​2019 CrossRefPubMed
go back to reference Spijker S (2011) Dissection of rodent brain regions. In: Li K (ed) Neuroproteomics. Neuromethods, vol 57. Humana Press, Totowa, NJ, pp 13–26CrossRef Spijker S (2011) Dissection of rodent brain regions. In: Li K (ed) Neuroproteomics. Neuromethods, vol 57. Humana Press, Totowa, NJ, pp 13–26CrossRef
go back to reference Zhou JH, Hao ML, Zhao S, Chen HE, Chen D, Ying L, Sun Q, Wang WT (2013) Effects of curcumin on pneumocyte apoptosis and CHOP in pulmonary ischemia/reperfusion injury of mice. Zhongguo Ying Yong Sheng Li Xue Za Zhi 29(4):318–323PubMed Zhou JH, Hao ML, Zhao S, Chen HE, Chen D, Ying L, Sun Q, Wang WT (2013) Effects of curcumin on pneumocyte apoptosis and CHOP in pulmonary ischemia/reperfusion injury of mice. Zhongguo Ying Yong Sheng Li Xue Za Zhi 29(4):318–323PubMed
Metadata
Title
Curcumin attenuates cytoplasmic/endoplasmic reticulum stress, apoptosis and cholinergic dysfunction in diabetic rat hippocampus
Authors
Walaa A. Keshk
Walaa S. Elseady
Naglaa I. Sarhan
Doaa H. Zineldeen
Publication date
01-04-2020
Publisher
Springer US
Keyword
Diabetes
Published in
Metabolic Brain Disease / Issue 4/2020
Print ISSN: 0885-7490
Electronic ISSN: 1573-7365
DOI
https://doi.org/10.1007/s11011-020-00551-0

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