RT journal article
T1 Differential central pathology and cognitive impairment in pre-diabetic and diabetic mice
A1 Ramos-Rodríguez, Juan José
A1 Ortiz, Oscar
A1 Jiménez Palomares, Margarita
A1 Kay, Kevin R
A1 Berrocoso Domínguez, Esther María
A1 Murillo-Carretero, María Isabel
A1 Perdomo, Germán
A1 Spires-Jones, Tara
A1 Cozar-Castellano, Irene
A1 Lechuga Sancho, Alfonso María
A1 García Alloza, Mónica
A2 BiomedicinaBiotecnología y Salud Pública
K1 Alzheimer's disease
K1 Brain atrophy
K1 Spontaneous hemorrhage
K1 Tau phosphorylation
K1 Type 2 diabetes
K1 Vascular dementia
AB 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.
PB Elsevier
SN 10.1016/j.psyneuen.2013.05.010
YR 2013
FD 2013-06-21
LK http://hdl.handle.net/10498/34807
UL http://hdl.handle.net/10498/34807
LA eng
DS Repositorio Institucional de la Universidad de Cádiz
RD 10-nov-2026