title: Hippocampal calcium dysregulation at the nexus of diabetes and brain aging.
abstract: Recently it has become clear that conditions of insulin resistance/metabolic syndrome, obesity and diabetes, are linked with moderate cognitive impairment in normal aging and elevated risk of Alzheimer's disease. It appears that a common feature of these conditions is impaired insulin signaling, affecting the brain as well as peripheral target tissues. A number of studies have documented that insulin directly affects brain processes and that reduced insulin signaling results in impaired learning and memory. Several studies have also shown that diabetes induces Ca(2+) dysregulation in neurons. Because brain aging is associated with substantial Ca(2+) dyshomeostasis, it has been proposed that impaired insulin signaling exacerbates or accelerates aging-related Ca(2+) dyshomeostasis. However, there have been few studies examining insulin interactions with Ca(2+) regulation in aging animals. We have been testing predictions of the Ca(2+) dysregulation/diabetes/brain aging hypothesis and have found that insulin and insulin-sensitizers (thiazolidinediones) target several hippocampal Ca(2+)-related processes affected by aging. The drugs appear able to reduce the age-dependent increase in Ca(2+) transients and the Ca(2+) -sensitive afterhyperpolarization. Thus, while additional testing is needed, the results to date are consistent with the view that strategies that enhance insulin signaling can counteract the effect of aging on Ca(2+) dysregulation.
authors.affiliation: Department of Molecular and Biomedical Pharmacology, MS 313, 800 Rose Street, University of Kentucky Medical Center, Lexington, KY 40536, United States. Electronic address: othibau@uky.edu.
authors.forename: Olivier
authors.initials: O
authors.lastname: Thibault
authors.affiliation: Department of Molecular and Biomedical Pharmacology, MS 313, 800 Rose Street, University of Kentucky Medical Center, Lexington, KY 40536, United States.
authors.forename: Katie L
authors.initials: KL
authors.lastname: Anderson
authors.affiliation: Department of Molecular and Biomedical Pharmacology, MS 313, 800 Rose Street, University of Kentucky Medical Center, Lexington, KY 40536, United States.
authors.forename: Chris
authors.initials: C
authors.lastname: DeMoll
authors.affiliation: Department of Molecular and Biomedical Pharmacology, MS 313, 800 Rose Street, University of Kentucky Medical Center, Lexington, KY 40536, United States.
authors.forename: Lawrence D
authors.initials: LD
authors.lastname: Brewer
authors.affiliation: Department of Molecular and Biomedical Pharmacology, MS 313, 800 Rose Street, University of Kentucky Medical Center, Lexington, KY 40536, United States.
authors.forename: Philip W
authors.initials: PW
authors.lastname: Landfield
authors.affiliation: Department of Molecular and Biomedical Pharmacology, MS 313, 800 Rose Street, University of Kentucky Medical Center, Lexington, KY 40536, United States.
authors.forename: Nada M
authors.initials: NM
authors.lastname: Porter
mesh_terms: D000375:Aging / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003071:Cognition; D003920:Diabetes Mellitus / Q000378:metabolism* / Q000503:physiopathology; D006624:Hippocampus / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D007328:Insulin / Q000378:metabolism
chemical_list: D007328:Insulin; D002118:Calcium
keywords: Afterhyperpolarization; Aging; Cognition; Imaging; Learning; Thiazolidinediones