Alzheimer's disease and type 2 diabetes-related alterations in brain mitochondria, autophagy and synaptic markers

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1852

Article

Carvalho, Cristina¹  Santos, Maria S.^1,2  Oliveira, Catarina R.^1,3  Moreira, Paula I.^1,4 

[1] Univ Coimbra, CNC Ctr Neurosci & Cell Biol, P-3004504 Coimbra, Portugal

[2] Univ Coimbra, Fac Sci & Technol, Dept Life Sci, P-3004504 Coimbra, Portugal

[3] Univ Coimbra, Fac Med, Biochem Lab, P-3004504 Coimbra, Portugal

[4] Univ Coimbra, Fac Med, Physiol Lab, P-3004504 Coimbra, Portugal

关键词: Alzheimer's disease;    Autophagy;    Mitochondrial function and biogenesis;    Synaptic integrity;    Type 2 diabetes;   

DOI  :  10.1016/j.bbadis.2015.05.001

来源: Elsevier

【 摘 要 】

We aimed to investigate mitochondrial function, biogenesis and autophagy in the brain of type 2 diabetes (T2D) and Alzheimer's disease (AD) mice. Isolated brain mitochondria and homogenates from cerebral cortex and hippocampus of wild-type (WT), triple transgenic AD (3xTg-AD) and T2D mice were used to evaluate mitochondrial functional parameters and protein levels of mitochondrial biogenesis, autophagy and synaptic integrity markers, respectively. A significant decrease in mitochondria( respiration, membrane potential and energy levels was observed in T2D and 3xTg-AD mice. Also, a significant decrease in the levels of autophagy-related protein 7 (ATG7) and glycosylated lysosomal membrane protein 1 (LAMP1) was observed in cerebral cortex and hippocampus of T2D and 3xTg-AD mice. Moreover, both brain regions of 3xTg-AD mice present lower levels of nuclear respiratory factor (NRF) 1 while the levels of NRF2 are lower in both brain regions of T2D and 3xTg-AD mice. A decrease in mitochondrial encoded, nicotinamide adenine dinucleotide dehydrogenase subunit 1 (ND1) was also observed in T2D and 3xTg-AD mice although only statistically significant in T2D cortex. Furthermore, a decrease in the levels of postsynaptic density protein 95 (PSD95) in the cerebral cortex of 3xTg-AD mice and in hippocampus of T2D and 3xTg-AD mice and a decrease in the levels of synaptosomal-associated protein 25 (SNAP 25) in the hippocampus of T2D and 3xTg-AD mice were observed suggesting synaptic integrity loss. These results support the idea that alterations in mitochondrial function, biogenesis and autophagy cause synaptic damage in AD and T2D. (C) 2015 Elsevier B.V. All rights reserved.

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