The dipeptidyl peptidase-4 inhibitor, linagliptin, improves cognitive impairment in streptozotocin-induced diabetic mice by inhibiting oxidative stress and microglial activation

Autor: Tomoaki Inoue, Mayumi Yamato, Ryoichi Takayanagi, Shinichiro Kimura, Yohei Minami, Hiroaki Makimura, Eiichi Hayashida, Fuminori Hyodo, Toyoshi Inoguchi, Makoto Ide, Noriyuki Sonoda
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Blood Glucose
Male
0301 basic medicine
Physiology
Dipeptidyl peptidase-4 inhibitor
Water maze
Pharmacology
medicine.disease_cause
Diagnostic Radiology
Mice
Endocrinology
0302 clinical medicine
Animal Cells
Immune Physiology
Medicine and Health Sciences
Medicine
Cognitive Impairment
Innate Immune System
Oxidase test
Multidisciplinary
Cognitive Neurology
Radiology and Imaging
Brain
Magnetic Resonance Imaging
Neurology
Physiological Parameters
Cytokines
Microglia
Cellular Types
Research Article
medicine.drug
Endocrine Disorders
Imaging Techniques
Cognitive Neuroscience
Science
Immunology
Linagliptin
Glial Cells
Research and Analysis Methods
Streptozocin
Diabetes Mellitus
Experimental
Proinflammatory cytokine
03 medical and health sciences
Diagnostic Medicine
Diabetes mellitus
Mental Health and Psychiatry
Diabetes Mellitus
Animals
Maze Learning
Microglial Cells
Dipeptidyl-Peptidase IV Inhibitors
Tumor Necrosis Factor-alpha
business.industry
Body Weight
NADPH Oxidases
Biology and Life Sciences
Cell Biology
Molecular Development
Streptozotocin
medicine.disease
Mice
Inbred C57BL
Oxidative Stress
030104 developmental biology
Metabolic Disorders
Immune System
Cognitive Science
Dementia
Lipid Peroxidation
business
030217 neurology & neurosurgery
Oxidative stress
Neuroscience
Developmental Biology
Zdroj: PLoS ONE, Vol 15, Iss 2, p e0228750 (2020)
PLoS ONE
ISSN: 1932-6203
Popis: Objective Accumulating epidemiological studies have demonstrated that diabetes is an important risk factor for dementia. However, the underlying pathological and molecular mechanisms, and effective treatment, have not been fully elucidated. Herein, we investigated the effect of the dipeptidyl peptidase-4 (DPP-4) inhibitor, linagliptin, on diabetes-related cognitive impairment. Method Streptozotocin (STZ)-induced diabetic mice were treated with linagliptin (3 mg/kg/24 h) for 17 weeks. The radial arm water maze test was performed, followed by evaluation of oxidative stress using DNP-MRI and the expression of NAD(P)H oxidase components and proinflammatory cytokines and of microglial activity. Results Administration of linagliptin did not affect the plasma glucose and body weight of diabetic mice; however, it improved cognitive impairment. Additionally, linagliptin reduced oxidative stress and the mRNA expression of NAD(P)H oxidase component and TNF-α, and the number and body area of microglia, all of which were significantly increased in diabetic mice. Conclusions Linagliptin may have a beneficial effect on diabetes-related dementia by inhibiting oxidative stress and microglial activation, independently of glucose-lowering.
Databáze: OpenAIRE
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