High-fat diets impair spatial learning in the radial-arm maze in mice

Valladolid‐Acebes, Ismael; Stucchi, Paula; Cano, Victoria; Fernández-Alfonso, Marı́a S.; Merino, Beatriz; Gil‐Ortega, Marta; Fole, Alberto; Morales, Lidia; Ruiz‐Gayo, Mariano; Olmo, Nuria Del

doi:10.1016/j.nlm.2010.11.007

Cited by 142 publications

(101 citation statements)

References 34 publications

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“…A high fat diet (HFD) is one of main factors that can promote obesity and previous studies have shown that such a diet can produce learning and memory impairments in rodents [21][22][23][24]. HFD was previously shown to induce a remarkable brain insulin resistance as well as spatial memory impairment in a normal mouse or a transgenic model of AD [25].…”

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confidence: 99%

Insulin Resistance as Common Molecular Denominator Linking Obesity to Alzheimer’s Disease

Nuzzo

Picone

Baldassano³

et al. 2015

CAR

105

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Alzheimer's disease (AD) is an aging-related multi-factorial disorder to which metabolic factors contribute at what has canonically been considered a centrally mediated process. Although the exact underlying mechanisms are still unknown, obesity is recognized as a risk factor for AD and the condition of insulin resistance seems to be the link between the two pathologies. Using mice with high fat diet (HFD) obesity we dissected the molecular mechanisms shared by the two disorders. Brains of HFD fed mice showed elevated levels of APP and Aβ 40 /Aβ 42 together with BACE, GSK3β and Tau proteins involved in APP processing and Aβ accumulation. Immunofluorescence, Thioflavin T staining experiments, confirmed increased Aβ generation, deposition in insoluble fraction and plaques formation in both the hippocampus and the cerebral cortex of HFD mice. Presence of Aβ 40 and Aβ 42 in the insoluble fraction was also shown by ELISA assay. Brain insulin resistance was demonstrated by reduced presence of insulin receptor (IRs) and defects in Akt-Foxo3a insulin signaling. We found reduced levels of phospho-Akt and increased levels of Foxo3a in the nuclei of neurons where proapototic genes were activated. Dysregulation of different genes related to insulin resistance, especially those involved in inflammation and adipocytokines synthesis were analyzed by Profiler PCR array. Further, HFD induced oxidative stress, mitochondrial dysfunction and dynamics as demonstrated by expression of biomarkers involved in these processes. Here, we provide evidence that obesity and AD markers besides insulin resistance are associated with inflammation, adipokine dyshomeostasis, oxidative stress and mitochondrial dysfunction, all mechanisms leading to neurodegeneration.

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Section: Please Provide Corresponding Author(s) Photographmentioning

confidence: 99%

Insulin Resistance as Common Molecular Denominator Linking Obesity to Alzheimer’s Disease

Nuzzo

Picone

Baldassano³

et al. 2015

CAR

105

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“…Prior to maze experiment and in order to enhance motivation for food in the 8-arm radial maze, animals were kept on a restricted diet (water was freely available), and body weight was reduced to 80-85% of normal weight. 13 Preliminary training (10 min, 4 days) for each rat involved handling the rats and then placing them as a group in an open field, followed by individual placement on the central platform of the maze (with food pellets placed throughout the maze). By the 4 th day, rats were capable of running to the ends of the arms.…”

Section: Radial Maze Taskmentioning

confidence: 99%

Memory-related gene expression profile of the male rat hippocampus induced by teeth extraction and occlusal support recovery

Iida

Hara

Araki

et al. 2014

Archives of Oral Biology

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Objectives: The present study aimed to identify the effect of memory-related genes on male rats tested for spatial memory with either molar teeth extraction or its restoration by occlusal support using experimental dentures.Design: Memory-related genes were detected from hippocampi of Male Wistar rats (exposed to teeth extraction with or without dentures, or no extraction [control]) (7-week old) after behavioral testing (via the radial maze task) using DNA microarray. The time course of the expression of these genes was evaluated by quantitative real-time PCR (on 49-weeks old rats). Results:In preliminary experiments to determine which memory genes are affected by spatial memory training, DNA microarray analysis revealed that thyrotropin-releasing hormone (Trh) and tenascin XA (Tnxa) were up-regulated and Neuronatin (Nnat) and S100a9 were down-regulated after the maze training. The expression of Tnxa, Nnat, and Conclusion:These results demonstrated that Trh, Tnxa, and Nnat genes were affected according to the degree of memory in male rats. This study also indicated that S100a9 is a memory-related gene, which is affected by the presence of occlusal support.

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“…Several previous studies have demonstrated that insulin resistance is associated with learning and memory decline , Stranahan et al 2008, Valladolid-Acebes et al 2011. In addition, increasing amounts of evidence demonstrate an association between dementia and T2DM (Janson et al 2004, Zhao & Townsend 2009, Kim et al 2010.…”

Section: Introductionmentioning

confidence: 98%

DPP-4 inhibitors improve cognition and brain mitochondrial function of insulin-resistant rats

Pintana

Apaijai²,

Chattipakorn³

2013

Journal of Endocrinology

172

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Recent evidence has demonstrated that insulin resistance is related to the development of type 2 diabetes mellitus. Our previous study found that high-fat diet (HFD) consumption caused not only peripheral and brain insulin resistance but also brain mitochondrial dysfunction and cognitive impairment. Vildagliptin and sitagliptin, dipeptidyl-peptidase-4 inhibitors, are recently developed anti-diabetic drugs. However, the effects of both drugs on cognitive behaviors and brain mitochondrial function in HFD-induced insulin-resistant rats have not yet been investigated. Sixty male Wistar rats were divided into two groups to receive either normal diet or HFD for 12 weeks. Rats in each group were then further divided into three treatment groups to receive either vehicle, vildagliptin (3 mg/kg per day), or sitagliptin (30 mg/kg per day) for 21 days. The cognitive behaviors of the rats were tested using the Morris Water Maze test. Blood samples were collected to determine metabolic parameters and plasma oxidative stress levels. Upon completion of the study, the animals were killed and the brains were removed to investigate brain and hippocampal mitochondrial function as well as to determine oxidative stress levels. We demonstrated that both drugs significantly improved the metabolic parameters and decreased circulating and brain oxidative stress levels in HFD-induced insulin-resistant rats. In addition, both drugs completely prevented brain and hippocampal mitochondrial dysfunction and equally improved the learning behaviors impaired by the HFD. Our findings suggest that the inhibition of dipeptidyl-peptidase-4 enzymes with vildagliptin or sitagliptin in insulinresistant rats not only increases peripheral insulin sensitivity but also decreases brain dysfunction. Key Words" insulin resistance " high-fat diet " DDP-4 inhibitors " memory decline " brain mitochondrial dysfunction

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High-fat diets impair spatial learning in the radial-arm maze in mice

Cited by 142 publications

References 34 publications

Insulin Resistance as Common Molecular Denominator Linking Obesity to Alzheimer’s Disease

Insulin Resistance as Common Molecular Denominator Linking Obesity to Alzheimer’s Disease

Memory-related gene expression profile of the male rat hippocampus induced by teeth extraction and occlusal support recovery

DPP-4 inhibitors improve cognition and brain mitochondrial function of insulin-resistant rats

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