Vascular, Oxidative, and Synaptosomal Abnormalities During Aging and the Progression of Type 2 Diabetes

Author(s): Cristina Carvalho, Sonia Catarina Correia, Maria Sancha Santos, Ines Baldeiras, Catarina Resende Oliveira, Raquel Seica, Paula Isabel Moreira.

Journal Name: Current Neurovascular Research

Volume 11 , Issue 4 , 2014

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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.

Keywords: Aging, brain vessels, neurodegeneration, oxidative stress, synaptosomes, type 2 diabetes.

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Article Details

VOLUME: 11
ISSUE: 4
Year: 2014
Page: [330 - 339]
Pages: 10
DOI: 10.2174/1567202611666140903122801
Price: $58

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