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

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. Theref...

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Vydané v:	Metabolic brain disease Ročník 35; číslo 4; s. 637 - 647
Hlavní autori:	Keshk, Walaa A., Elseady, Walaa S., Sarhan, Naglaa I., Zineldeen, Doaa H.
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	New York Springer US 01.04.2020 Springer Nature B.V
Predmet:	Activating transcription factor 4 Activating Transcription Factor 4 - genetics Activating Transcription Factor 4 - metabolism Animals Anticancer properties Antioxidants Apoptosis Apoptosis - drug effects BAX protein Bcl-2 protein bcl-2-Associated X Protein - metabolism Bcl-x protein Biochemistry Biomedical and Life Sciences Biomedicine Blood Glucose - metabolism CCAAT/enhancer-binding protein Cellular stress response Central nervous system Cerebrovascular diseases Cerebrovascular system Choline Choline O-Acetyltransferase - genetics Choline O-Acetyltransferase - metabolism Cholinergics Cognition Complications Curcumin Curcumin - pharmacology Dementia disorders Diabetes Diabetes mellitus Diabetes Mellitus, Experimental - genetics Diabetes Mellitus, Experimental - metabolism Endoplasmic reticulum Endoplasmic Reticulum Stress - drug effects Gene expression Glucose Heat shock proteins Heat-Shock Proteins - genetics Heat-Shock Proteins - metabolism Hippocampus Hippocampus - drug effects Hippocampus - metabolism Homology HSP70 Heat-Shock Proteins - metabolism Hsp70 protein Inflammation Interferon Interferon-gamma - metabolism Male Metabolic Diseases Neurodegeneration Neurology Neurosciences Oncology Original Article Oxidants Oxidizing agents Peritoneum Protective Agents - pharmacology Proteins Proto-Oncogene Proteins c-bcl-2 - genetics Proto-Oncogene Proteins c-bcl-2 - metabolism Rats Rats, Wistar Streptozocin Transcription Factor CHOP - metabolism γ-Interferon CCAAT-enhancer-binding protein homologous protein (CHOP) Neurodegeneration Glucose-regulated proteins78 (GRP78) Diabetes mellitus Activating transcription factor 4 (ATF-4) Choline acetyl transferase (ChAT)
ISSN:	0885-7490, 1573-7365, 1573-7365
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Shrnutí:	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.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	0885-7490 1573-7365 1573-7365
DOI:	10.1007/s11011-020-00551-0