title: Quercetin ameliorates chronic unpredicted stress-mediated memory dysfunction in male Swiss albino mice by attenuating insulin resistance and elevating hippocampal GLUT4 levels independent of insulin receptor expression.
abstract: Chronic stress is associated with impaired neuronal functioning, altered insulin signaling, and behavioral dysfunction. Quercetin has shown neuroprotective and antidiabetic effects, besides modulating cognition and insulin signaling. Therefore, in the present study, we explored whether or not quercetin ameliorates stress-mediated cognitive dysfunction and explored the underlying mechanism. Swiss albino male mice were subjected to an array of unpredicted stressors for 21days, during which 30mg/kg quercetin treatment was given orally. The effect of chronic unpredicted stress (CUS) and quercetin treatment on cognition were evaluated using novel object recognition (NOR) and Morris water maze (MWM) tests. Hippocampal neuronal integrity was observed by histopathological examination. Blood glucose, serum corticosterone, and insulin levels were measured by commercial kits and insulin resistance was evaluated in terms of HOMA-IR index. Hippocampal insulin signaling was determined by immunofluorescence staining. CUS induced significant cognitive dysfunction (NOR and MWM) and severely damaged hippocampal neurons, especially in the CA3 region. Quercetin treatment alleviated memory dysfunction and rescued neurons from CUS-mediated damage. Fasting blood glucose, serum corticosterone, and serum insulin were significantly elevated in stressed animals, besides, having significantly higher HOMA-IR index, suggesting the development of insulin resistance. Quercetin treatment alleviated insulin resistance and attenuated altered biochemical parameters. CUS markedly down-regulated insulin signaling in CA3 region and quercetin treatment improved neuronal GLUT4 expression, which seemed to be independent of insulin and insulin receptor levels. These results suggest that intact insulin functioning in the hippocampus is essential for cognitive functions and quercetin improves CUS-mediated cognitive dysfunction by modulating hippocampal insulin signaling.
authors.affiliation: Department of Bioinformatics, Biotechnology and Pharmacy, Jaypee University of Information Technology, Waknaghat, Solan, Himachal Pradesh -173234, India.
authors.forename: Vineet
authors.initials: V
authors.lastname: Mehta
authors.affiliation: Department of Bioinformatics, Biotechnology and Pharmacy, Jaypee University of Information Technology, Waknaghat, Solan, Himachal Pradesh -173234, India.
authors.forename: Arun
authors.initials: A
authors.lastname: Parashar
authors.affiliation: Department of Bioinformatics, Biotechnology and Pharmacy, Jaypee University of Information Technology, Waknaghat, Solan, Himachal Pradesh -173234, India.
authors.forename: Arun
authors.initials: A
authors.lastname: Sharma
authors.affiliation: Department of Bioinformatics, Biotechnology and Pharmacy, Jaypee University of Information Technology, Waknaghat, Solan, Himachal Pradesh -173234, India.
authors.forename: Tiratha Raj
authors.initials: TR
authors.lastname: Singh
authors.affiliation: Department of Bioinformatics, Biotechnology and Pharmacy, Jaypee University of Information Technology, Waknaghat, Solan, Himachal Pradesh -173234, India. Electronic address: m_udayabanu@rediffmail.com.
authors.forename: Malairaman
authors.initials: M
authors.lastname: Udayabanu
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001522:Behavior, Animal; D056654:CA3 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism*; D060825:Cognitive Dysfunction / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D051275:Glucose Transporter Type 4 / Q000187:drug effects / Q000378:metabolism*; D007333:Insulin Resistance; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D011794:Quercetin / Q000494:pharmacology*; D011972:Receptor, Insulin / Q000378:metabolism*; D013315:Stress, Psychological / Q000150:complications / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology
chemical_list: D000975:Antioxidants; D051275:Glucose Transporter Type 4; C495693:Slc2a4 protein, mouse; D011794:Quercetin; D011972:Receptor, Insulin
keywords: Chronic unpredicted stress; Cognition; GLUT4; Hippocampus; Immunofluorescence; Insulin; Insulin resistance; Learning and memory; Quercetin