title: Carnosine ameliorates cognitive deficits in streptozotocin-induced diabetic rats: Possible involved mechanisms.
abstract: Diabetic patients are at increased risk to develop cognitive deficit and senile dementia. This study was planned to assess the benefits of chronic carnosine administration on prevention of learning and memory deterioration in streptozotocin (STZ)-diabetic rats and to explore some of the involved mechanisms. Rats were divided into 5 groups: i.e., control, carnosine100-treated control, diabetic, and carnosine-treated diabetics (50 and 100mg/kg). Carnosine was injected i.p. at doses of 50 or 100mg/kg for 7 weeks, started 1 week after induction of diabetes using streptozotocin. Treatment of diabetic rats with carnosine at a dose of 100mg/kg at the end of the study lowered serum glucose, improved spatial recognition memory in Y maze, improved retention and recall in elevated plus maze, and prevented reduction of step-through latency in passive avoidance task. Furthermore, carnosine at a dose of 100mg/kg reduced hippocampal acetylcholinesterase (AChE) activity, lowered lipid peroxidation, and improved superoxide dismutase (SOD) activity and non-enzymatic antioxidant defense element glutathione (GSH), but not activity of catalase. Meanwhile, hippocampal level of nuclear factor-kappaB (NF-κB), tumor necrosis factor α (TNF-α), and glial fibrillary acidic protein (GFAP) decreased and level of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and heme oxygenase 1 (HO-1) increased upon treatment of diabetic group with carnosine at a dose of 100mg/kg. Taken together, chronic carnosine treatment could ameliorate learning and memory disturbances in STZ-diabetic rats through intonation of NF-κB/Nrf2/HO-1 signaling cascade, attenuation of astrogliosis, possible improvement of cholinergic function, and amelioration of oxidative stress and neuroinflammation.
authors: Neurophysiology Research Center, Shahed University, Tehran, Iran.
authors: Siamak
authors: S
authors: Ahshin-Majd
authors: School of Medicine, Shahed University, Tehran, Iran.
authors: Samira
authors: S
authors: Zamani
authors: School of Medicine, Shahed University, Tehran, Iran.
authors: Taktom
authors: T
authors: Kiamari
authors: Neurophysiology Research Center, Shahed University, Tehran, Iran. Electronic address: kiasalari@shahed.ac.ir.
authors: Zahra
authors: Z
authors: Kiasalari
authors: Department of Physiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
authors: Tourandokht
authors: T
authors: Baluchnejadmojarad
authors: Neurophysiology Research Center, Shahed University, Tehran, Iran. Electronic address: mehjour@yahoo.com.
authors: Mehrdad
authors: M
authors: Roghani
mesh_terms: D000818:Animals; D002336:Carnosine / Q000494:pharmacology* / Q000627:therapeutic use; D003071:Cognition / Q000187:drug effects; D003072:Cognition Disorders / Q000209:etiology / Q000517:prevention & control*; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy*; D004353:Drug Evaluation, Preclinical; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018782:Maze Learning; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018384:Oxidative Stress; D017208:Rats, Wistar; D013311:Streptozocin
chemical_list: D018696:Neuroprotective Agents; D013311:Streptozocin; D002336:Carnosine
keywords: Carnosine; Cognition; Diabetes mellitus; Learning and memory; Streptozotocin