title: Central proliferation and neurogenesis is impaired in type 2 diabetes and prediabetes animal models.
abstract: Type 2 diabetes (T2D) is an important risk factor to suffer dementia, including Alzheimer's disease (AD), and some neuropathological features observed in dementia could be mediated by T2D metabolic alterations. Since brain atrophy and impaired neurogenesis have been observed both T2D and AD we analyzed central nervous system (CNS) morphological alterations in the db/db mice (leptin receptor KO mice), as a model of long-term insulin resistance and T2D, and in C57Bl6 mice fed with high fat diet (HFD), as a model of diet induced insulin resistance and prediabetes. Db/db mice showed an age-dependent cortical and hippocampal atrophy, whereas in HFD mice cortex and hippocampus were preserved. We also detected increased neurogenesis and cell proliferation rates in young db/db mice when compared with control littermates. Our study shows that metabolic parameters serve as predictors of both atrophy and altered proliferation and neurogenesis in the CNS. Moreover in the cortex, atrophy, cell proliferation and neurogenesis were significantly correlated. Our data suggest that T2D may underline some of the pathological features observed in the dementia process. They also support that blood glucose control in elderly patients could help to slow down dementia evolution and maybe, improve its prognosis.
authors.affiliation: Division of Physiology, Dpt. Biomedicine, Biotechnology and Public Health, Institute of Biomolecules (INBIO), School of Medicine, University of Cadiz, Cadiz, Spain.
authors.forename: Juan Jose
authors.initials: JJ
authors.lastname: Ramos-Rodriguez
authors.affiliation: Division of Physiology, Dpt. Biomedicine, Biotechnology and Public Health, Institute of Biomolecules (INBIO), School of Medicine, University of Cadiz, Cadiz, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Molina-Gil
authors.affiliation: Division of Physiology, Dpt. Biomedicine, Biotechnology and Public Health, Institute of Biomolecules (INBIO), School of Medicine, University of Cadiz, Cadiz, Spain.
authors.forename: Oscar
authors.initials: O
authors.lastname: Ortiz-Barajas
authors.affiliation: Institute de Biology and Molecular Genetics, University of Valladolid-CSIC, Valladolid, Spain.
authors.forename: Margarita
authors.initials: M
authors.lastname: Jimenez-Palomares
authors.affiliation: Dpt. of Inorganic and Organic Chemistry, and Biochemistry, University of Castilla La Mancha, Toledo, Spain.
authors.forename: German
authors.initials: G
authors.lastname: Perdomo
authors.affiliation: Institute de Biology and Molecular Genetics, University of Valladolid-CSIC, Valladolid, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Cozar-Castellano
authors.affiliation: Department of Pediatrics, School of Medicine, University of Cadiz, Cadiz, Spain.
authors.forename: Alfonso Maria
authors.initials: AM
authors.lastname: Lechuga-Sancho
authors.affiliation: Division of Physiology, Dpt. Biomedicine, Biotechnology and Public Health, Institute of Biomolecules (INBIO), School of Medicine, University of Cadiz, Cadiz, Spain.
authors.forename: Monica
authors.initials: M
authors.lastname: Garcia-Alloza
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D007124:Immunoenzyme Techniques; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008820:Mice, Obese; D055495:Neurogenesis / Q000502:physiology*; D011236:Prediabetic State / Q000503:physiopathology*; D054411:Receptors, Leptin / Q000502:physiology
chemical_list: D001786:Blood Glucose; D007328:Insulin; D054411:Receptors, Leptin; C515447:leptin receptor, mouse