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

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read More Add to Saved list
  • Additional Information
    • Source:
      Publisher: Elsevier Pub. Co Country of Publication: Netherlands NLM ID: 0217513 Publication Model: Print-Electronic Cited Medium: Print ISSN: 0006-3002 (Print) Linking ISSN: 00063002 NLM ISO Abbreviation: Biochim Biophys Acta Subsets: MEDLINE
    • Publication Information:
      Original Publication: Amsterdam : Elsevier Pub. Co.
    • Subject Terms:
      Alzheimer Disease*/complications ; Alzheimer Disease*/metabolism ; Alzheimer Disease*/pathology ; Brain*/metabolism ; Brain*/pathology ; Brain*/ultrastructure ; Diabetes Mellitus, Type 2*/complications ; Diabetes Mellitus, Type 2*/metabolism ; Diabetes Mellitus, Type 2*/pathology; Autophagy/*physiology ; Biomarkers/*metabolism ; Mitochondria/*pathology ; Synapses/*metabolism; Animals ; Diabetes Mellitus, Experimental/complications ; Diabetes Mellitus, Experimental/metabolism ; Diabetes Mellitus, Experimental/pathology ; Disease Models, Animal ; Male ; Mice ; Mice, Transgenic ; Mitochondria/metabolism
    • Abstract:
      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 mitochondrial 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.
      (Copyright © 2015 Elsevier B.V. All rights reserved.)
    • Contributed Indexing:
      Keywords: Alzheimer's disease; Autophagy; Mitochondrial function and biogenesis; Synaptic integrity; Type 2 diabetes
    • Accession Number:
      0 (Biomarkers)
    • Publication Date:
      Date Created: 20150512 Date Completed: 20150911 Latest Revision: 20161126
    • Publication Date:
      20240628
    • Accession Number:
      10.1016/j.bbadis.2015.05.001
    • Accession Number:
      25960150