title: Differential central pathology and cognitive impairment in pre-diabetic and diabetic mice.
abstract: Although age remains the main risk factor to suffer Alzheimer's disease (AD) and vascular dementia (VD), type 2 diabetes (T2D) has turned up as a relevant risk factor for dementia. However, the ultimate underlying mechanisms for this association remain unclear. In the present study we analyzed central nervous system (CNS) morphological and functional consequences of long-term insulin resistance and T2D in db/db mice (leptin receptor KO mice). We also included C57Bl6 mice fed with high fat diet (HFD) and a third group of C57Bl6 streptozotocin (STZ) treated mice. Db/db mice exhibited pathological characteristics that mimic both AD and VD, including age dependent cognitive deterioration, brain atrophy, increased spontaneous hemorrhages and tau phosphorylation, affecting the cortex preferentially. A similar profile was observed in STZ-induced diabetic mice. Moreover metabolic parameters, such as body weight, glucose and insulin levels are good predictors of many of these alterations in db/db mice. In addition, in HFD-induced hyperinsulinemia in C57Bl6 mice, we only observed mild CNS alterations, suggesting that central nervous system dysfunction is associated with well established T2D. Altogether our results suggest that T2D may promote many of the pathological and behavioral alterations observed in dementia, supporting that interventions devoted to control glucose homeostasis could improve dementia progress and prognosis.
authors.affiliation: Division of Physiology, School of Medicine, University of Cadiz, Cádiz, Spain.
authors.forename: Juan Jose
authors.initials: JJ
authors.lastname: Ramos-Rodriguez
authors.forename: Oscar
authors.initials: O
authors.lastname: Ortiz
authors.forename: Margarita
authors.initials: M
authors.lastname: Jimenez-Palomares
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Kay
authors.forename: Esther
authors.initials: E
authors.lastname: Berrocoso
authors.forename: Maria Isabel
authors.initials: MI
authors.lastname: Murillo-Carretero
authors.forename: German
authors.initials: G
authors.lastname: Perdomo
authors.forename: Tara
authors.initials: T
authors.lastname: Spires-Jones
authors.forename: Irene
authors.initials: I
authors.lastname: Cozar-Castellano
authors.forename: Alfonso Maria
authors.initials: AM
authors.lastname: Lechuga-Sancho
authors.forename: Monica
authors.initials: M
authors.lastname: Garcia-Alloza
mesh_terms: D000818:Animals; D001284:Atrophy; D001921:Brain / Q000098:blood supply / Q000473:pathology*; D003072:Cognition Disorders / Q000139:chemically induced / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications / Q000378:metabolism / Q000473:pathology* / Q000523:psychology*; D059305:Diet, High-Fat; D006470:Hemorrhage / Q000139:chemically induced / Q000150:complications; D051379:Mice; D018345:Mice, Knockout; D010766:Phosphorylation; D054411:Receptors, Leptin / Q000235:genetics; D013311:Streptozocin; D013569:Synapses / Q000473:pathology; D016875:tau Proteins / Q000378:metabolism
chemical_list: C558298:Mapt protein, mouse; D054411:Receptors, Leptin; C515447:leptin receptor, mouse; D016875:tau Proteins; D013311:Streptozocin
keywords: Alzheimer's disease; Brain atrophy; Spontaneous hemorrhage; Tau phosphorylation; Type 2 diabetes; Vascular dementia