title: Mineralocorticoid receptor activation induces insulin resistance through c-Jun N-terminal kinases in response to chronic corticosterone: cognitive implications.
abstract: It is becoming evident that chronic exposure to glucocorticoids might not only result in insulin resistance or cognitive deficits, but also is considered as a risk factor for pathologies such as depression or Alzheimer's disease. In the present study, in vivo experiments using a non-invasive method of chronic administration of corticosterone in drinking water demonstrated that chronic corticosterone administration led to cognitive impairment in the novel object recognition test and insulin resistance, as shown by significant increases in plasma insulin levels and the homeostatic model assessment index, and decreased insulin receptor phosphorylation. Corticosterone treatment induced an increased expression of stress-activated c-Jun N-terminal kinase (JNK) in the hippocampus, accompanied by decreases in glycogen synthase kinase 3β, increases in pTau levels and increased neuronal cell death (caspase-3 activity). All these effects were reversed by the administration of a JNK1 inhibitor or by the mineralocorticoid receptor antagonist spironolactone. It is suggested that the mineralocorticoid receptors and JNK-mediated pathways are involved in the interaction of glucocorticoid-insulin resistance and the development of relevant cellular processes for Alzheimer's disease.
authors.affiliation: Department of Pharmacology, University of Navarra, Pamplona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Solas
authors.forename: G
authors.initials: G
authors.lastname: Gerenu
authors.forename: F J
authors.initials: FJ
authors.lastname: Gil-Bea
authors.forename: M J
authors.initials: MJ
authors.lastname: Ramírez
mesh_terms: D000818:Animals; D003072:Cognition Disorders / Q000139:chemically induced*; D003345:Corticosterone / Q000008:administration & dosage* / Q000009:adverse effects; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018161:Receptors, Mineralocorticoid / Q000378:metabolism*
chemical_list: D007328:Insulin; D018161:Receptors, Mineralocorticoid; D048031:JNK Mitogen-Activated Protein Kinases; D003345:Corticosterone