title: Mitochondrial Abnormalities and Synaptic Loss Underlie Memory Deficits Seen in Mouse Models of Obesity and Alzheimer's Disease.
abstract: Obesity is associated with impaired memory in humans, and obesity induced by high-fat diets leads to cognitive deficits in rodents and in mouse models of Alzheimer's disease (AD). However, it remains unclear how high-fat diets contribute to memory impairment. Therefore, we tested the effect of a high-fat diet on memory in male and female control non-transgenic (Non-Tg) and triple-transgenic AD (3xTgAD) mice and determined if a high-fat diet caused similar ultrastructural abnormalities to those observed in AD. Behavior was assessed in mice on control or high-fat diet at 4, 8, or 14 months of age and ultrastructural analysis at 8 months of age. A high-fat diet increased body weight, fat weight, and insulin levels with some differences in these metabolic responses observed between Non-Tg and 3xTgAD mice. In both sexes, high-fat feeding caused memory impairments in Non-Tg mice and accelerated memory deficits in 3xTgAD mice. In 3xTgAD mice, changes in hippocampal mitochondrial morphology were observed in capillaries and brain neuropil that were accompanied by a reduction in synapse number. A high-fat diet also caused mitochondria abnormalities and a reduction in synapse number in Non-Tg mice, but did not exacerbate the changes seen in 3xTgAD mice. Our data demonstrate that a high-fat diet affected memory in Non-Tg mice and produced similar impairments in mitochondrial morphology and synapse number comparable to those seen in AD mice, suggesting that the detrimental effects of a high-fat diet on memory might be due to changes in mitochondrial morphology leading to a reduction in synaptic number.
authors: Isaura V A
authors: IV
authors: Martins
authors: Jack
authors: J
authors: Rivers-Auty
authors: Stuart M
authors: SM
authors: Allan
authors: Catherine B
authors: CB
authors: Lawrence
mesh_terms: D000544:Alzheimer Disease / Q000150:complications* / Q000235:genetics / Q000473:pathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001786:Blood Glucose / Q000235:genetics; D001794:Blood Pressure / Q000235:genetics; D059305:Diet, High-Fat / Q000379:methods; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000473:pathology / Q000648:ultrastructure; D005260:Female; D006624:Hippocampus / Q000473:pathology / Q000648:ultrastructure*; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008569:Memory Disorders / Q000209:etiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000473:pathology* / Q000648:ultrastructure; D009765:Obesity / Q000209:etiology / Q000473:pathology*; D053764:Presenilin-1 / Q000235:genetics; D021641:Recognition, Psychology / Q000502:physiology; D012903:Smell / Q000502:physiology; D013569:Synapses / Q000473:pathology* / Q000648:ultrastructure; D016875:tau Proteins / Q000235:genetics
chemical_list: D016564:Amyloid beta-Protein Precursor; D001786:Blood Glucose; D007328:Insulin; D053764:Presenilin-1; D016875:tau Proteins
keywords: 3xTgAD; Alzheimer’s disease; Non-Tg; high-fat diet; memory; mitochondria; obesity; synapses