title: Alzheimer's disease and type 2 diabetes-related alterations in brain mitochondria, autophagy and synaptic markers.
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.
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Portugal. Electronic address: cristina.im.carvalho@gmail.com.
authors.forename: Cristina
authors.initials: C
authors.lastname: Carvalho
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Portugal; Department of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, Portugal.
authors.forename: Maria S
authors.initials: MS
authors.lastname: Santos
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Portugal; Laboratory of Biochemistry, Faculty of Medicine, University of Coimbra, Portugal.
authors.forename: Catarina R
authors.initials: CR
authors.lastname: Oliveira
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Portugal; Laboratory of Physiology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal. Electronic address: venta@ci.uc.pt.
authors.forename: Paula I
authors.initials: PI
authors.lastname: Moreira
mesh_terms: D000544:Alzheimer Disease / Q000150:complications / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001343:Autophagy / Q000502:physiology*; D015415:Biomarkers / Q000378:metabolism*; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology*; D013569:Synapses / Q000378:metabolism*
chemical_list: D015415:Biomarkers
keywords: Alzheimer's disease; Autophagy; Mitochondrial function and biogenesis; Synaptic integrity; Type 2 diabetes