title: Vascular, oxidative, and synaptosomal abnormalities during aging and the progression of type 2 diabetes.
abstract: Alterations in brain structure and function are a well-known long-term complication of type 2 diabetes (T2D). Although the mechanism(s) by which T2D lead(s) to cognitive dysfunction and neuronal cells degeneration continue(s) to be a matter of debate, vascular alterations emerged as major players in this scenario. This study was aimed to evaluate the antioxidant defenses and oxidative markers present in brain vessels and synaptosomes from 3- and 12-month-old Goto- Kakizaki (GK) rats, a spontaneous non-obese model of T2D, and Wistar control rats. A significant increase in manganese superoxide dismutase (MnSOD) activity and vitamin E levels and a significant decrease in aconitase and glutathione reductase (GR) activities, glutathione (GSH)/glutathione disulfide (GSSG) ratio, and GSH and malondialdehyde (MDA) levels were observed in brain vessels and synaptosomes from GK rats, and these effects were not significantly affected by aging. However, an age-dependent increase in hydrogen peroxide (H2O2) levels in both diabetic synaptosomes and vessels was observed. No significant alterations were observed in the activity of glutathione peroxidase (GPx) and GR in both brain vessels and synaptosomes from diabetic animals. In control rats, an age-dependent increase in the activity of GPx, GR, and MnSOD and vitamin E and MDA levels and an age-dependent decrease in GSH levels were observed in brain vessels. In contrast, a significant age-dependent increase in GSH levels and a decrease in vitamin E levels were observed in synaptosomes from control animals. Altogether, our results show that T2D and aging differently affect brain vessels and synaptosomes. However, both conditions increase the vulnerability of brain structures to degenerative events.
authors.forename: Cristina
authors.initials: C
authors.lastname: Carvalho
authors.forename: Sonia Catarina
authors.initials: SC
authors.lastname: Correia
authors.forename: Maria Sancha
authors.initials: MS
authors.lastname: Santos
authors.forename: Ines
authors.initials: I
authors.lastname: Baldeiras
authors.forename: Catarina Resende
authors.initials: CR
authors.lastname: Oliveira
authors.forename: Raquel
authors.initials: R
authors.lastname: Seica
authors.affiliation: Center for Neuroscience and Cell Biology, University of Coimbra 3004-504 & Laboratory of Physiology - Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal. pimoreira@fmed.uc.pt.
authors.forename: Paula Isabel
authors.initials: PI
authors.lastname: Moreira
mesh_terms: D000154:Aconitate Hydratase / Q000378:metabolism; D000367:Age Factors; D000375:Aging / Q000473:pathology*; D000818:Animals; D001808:Blood Vessels / Q000378:metabolism* / Q000473:pathology; D001921:Brain / Q000473:pathology*; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology*; D004195:Disease Models, Animal; D005978:Glutathione; D005979:Glutathione Peroxidase / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D011922:Rats, Mutant Strains; D017208:Rats, Wistar; D013574:Synaptosomes / Q000378:metabolism*; D045162:Thiazolidinediones / Q000378:metabolism; D014810:Vitamin E / Q000378:metabolism
chemical_list: C575035:(Z)2-(5-(4-methoxybenzylidene)-2,4-dioxothiazolidin-3-yl)acetic acid; D045162:Thiazolidinediones; D014810:Vitamin E; D006861:Hydrogen Peroxide; D005979:Glutathione Peroxidase; D000154:Aconitate Hydratase; D005978:Glutathione