title: Depression mediates impaired glucose tolerance and cognitive dysfunction: A neuromodulatory role of rosiglitazone.
abstract: Comorbidity of depression and diabetes is a serious risk factor worsening the complications such as cognitive function and locomotion. Treatment under this condition becomes extremely complicated. Insulin signaling and autophagy pathways are involved in modulation of learning and memory. Rosiglitazone (ROSI) ameliorate cognitive deficit associated with depression and insulin resistance. In the present study, we investigated the effect of ROSI against chronic unpredictable stress (CUS) induced depression as a risk factor for diabetes and behavioral dysfunctions. Adult male Swiss albino mice were exposed to CUS alongside ROSI (5mg/kg/day) treatment for 21days. Thereafter, animals were subjected to different behavioral studies to assess depressive like behavior, cognition and locomotion. The effect of ROSI on insulin signaling, autophagy and apoptosis were evaluated in the hippocampus. CUS resulted in depressive like behavior, cognitive impairment and hypolocomotion associated with oxidative stress, impaired glucose tolerance and hypercorticosteronemia. CUS significantly impaired hippocampal insulin signaling, membrane translocation of glucose transporter type 4 (GLUT4) as well as decreased the expression of autophagy5, autophagy7, B-cell lymphoma 2 and apoptosis inhibitory protein 2. ROSI significantly reduced depressive like behavior, postprandial blood glucose, hypercorticosteronemia, oxidative and inflammatory stress, and apoptosis in stressed mice. Moreover, ROSI treatment effectively improved hippocampal insulin signaling, GLUT4 membrane translocation and cognitive performance in depressed mice. ROSI administration might prove to be effective for neurological disorders associated with depressive like behavior and impaired glucose tolerance.
authors.affiliation: Department of Pharmacy, Jaypee University of Information Technology, Waknaghat, Himachal Pradesh, India; Department of Pharmacology, Lakshmi Narain College of Pharmacy, Bhopal, Madhya Pradesh, India.
authors.forename: Sita Sharan
authors.initials: SS
authors.lastname: Patel
authors.affiliation: Department of Pharmacy, Jaypee University of Information Technology, Waknaghat, Himachal Pradesh, India.
authors.forename: Vineet
authors.initials: V
authors.lastname: Mehta
authors.affiliation: Department of Biotechnology and Bioinformatics, Jaypee University of Information Technology, Waknaghat, Himachal Pradesh, India.
authors.forename: Harish
authors.initials: H
authors.lastname: Changotra
authors.affiliation: Department of Pharmacy, Jaypee University of Information Technology, Waknaghat, Himachal Pradesh, India. Electronic address: m_udayabanu@rediffmail.com.
authors.forename: Malairaman
authors.initials: M
authors.lastname: Udayabanu
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology; D003863:Depression / Q000188:drug therapy* / Q000209:etiology; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D008297:Male; D051379:Mice; D000077154:Rosiglitazone; D013315:Stress, Psychological / Q000150:complications*; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D045162:Thiazolidinediones; D000077154:Rosiglitazone
keywords: Chronic stress; Cognition; Depression; Glucose tolerance; Rosiglitazone