scholarly journals LPC-DHA/EPA-Enriched Diets Increase Brain DHA and Modulate Behavior in Mice That Express Human APOE4

2021 ◽  
Vol 15 ◽  
Author(s):  
Sarah B. Scheinman ◽  
Dhavamani Sugasini ◽  
Monay Zayed ◽  
Poorna C. R. Yalagala ◽  
Felecia M. Marottoli ◽  
...  
Keyword(s):  
Control Diet ◽  
The Novel ◽  
Krill Oil ◽  
Object Recognition Test ◽  
Beneficial Effects ◽  
Negative Results ◽  
Age Related ◽  
Improved Performance ◽  
Age Related Cognitive Decline

Compared with APOE3, APOE4 is associated with greater age-related cognitive decline and higher risk of neurodegenerative disorders. Therefore, development of supplements that target APOE genotype-modulated processes could provide a great benefit for the aging population. Evidence suggests a link between APOE genotype and docosahexaenoic acid (DHA); however, clinical studies with current DHA supplements have produced negative results in dementia. The lack of beneficial effects with current DHA supplements may be related to limited bioavailability, as the optimal form of DHA for brain uptake is lysophosphatidylcholine (LPC)-DHA. We previously developed a method to enrich the LPC-DHA content of krill oil through lipase treatment (LT-krill oil), which resulted in fivefold higher enrichment in brain DHA levels in wild-type mice compared with untreated krill oil. Here, we evaluated the effect of a control diet, diet containing krill oil, or a diet containing LT-krill oil in APOE3- and APOE4-targeted replacement mice (APOE-TR mice; treated from 4 to 12 months of age). We found that DHA levels in the plasma and hippocampus are lower in APOE4-TR mice and that LT-krill oil increased DHA levels in the plasma and hippocampus of both APOE3- and APOE4-TR mice. In APOE4-TR mice, LT-krill oil treatment resulted in higher levels of the synaptic vesicle protein SV2A and improved performance on the novel object recognition test. In conclusion, our data demonstrate that LPC-DHA/EPA-enriched krill oil can increase brain DHA and improve memory-relevant behavior in mice that express APOE4. Therefore, long-term use of LT-krill oil supplements may on some level protect against age-related neurodegeneration.

scholarly journals Beneficial effects of multisensory and cognitive stimulation on age-related cognitive decline in long-term-care institutions

2014 ◽  
pp. 309 ◽  
Author(s):  
Cristovam Picanço-Diniz ◽  
Thais Cristina Galdino De Oliveira ◽  
Fernanda Cabral Soares ◽  
Liliane Dias E Dias De Macedo ◽  
Domingos Luiz Wanderley Picanco Diniz ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Long Term Care ◽  
Cognitive Stimulation ◽  
Term Care ◽  
Beneficial Effects ◽  
Age Related ◽  
Age Related Cognitive Decline

scholarly journals Long-term associative memory in rats: effects of familiarization period in object-place-context recognition test

2019 ◽  
Author(s):  
Shota Shimoda ◽  
Takaaki Ozawa ◽  
Yukio Ichitani ◽  
Kazuo Yamada
Keyword(s):  
Recognition Memory ◽  
Recognition Test ◽  
Associative Memory ◽  
Associative Recognition ◽  
The Novel ◽  
Novelty Preference ◽  
Object Recognition Test ◽  
Spontaneous Recognition ◽  
Familiarization Period

AbstractSpontaneous recognition tests, which utilize rodents’ innate tendency to explore novelty, can evaluate not only simple non-associative recognition memory but also more complex associative memory in animals. In the present study, we investigated whether the length of the object familiarization period (sample phase) improved subsequent novelty discrimination in the spontaneous object, place, and object-place-context (OPC) recognition tests in rats. In the OPC test, rats showed a significant novelty preference only when the familiarization period was 30 min but not when it was 5 min or 15 min. However, the rats exhibited a successful discrimination between the stayed and replaced objects under 15 min and 30 min familiarization period conditions in the place recognition test and between the novel and familiar objects under all conditions of 5, 15 and 30 min in the object recognition test. Our results suggest that the extension of the familiarization period improves performance in the spontaneous recognition paradigms, and a longer familiarization period is necessary for long-term associative recognition memory than for non-associative memory.

scholarly journals Long-Term Feeding of a High-Fat Diet Ameliorated Age-Related Phenotypes in SAMP8 Mice

Nutrients ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1416
Author(s):  
Hideaki Oike ◽  
Yukino Ogawa ◽  
Kayo Azami
Keyword(s):  
Control Diet ◽  
Active Phase ◽  
Restricted Feeding ◽  
Long Term Effects ◽  
High Fat ◽  
Night Time ◽  
Age Related ◽  
Nutritional Studies ◽  
Samp8 Mice

High-fat diets (HFD) have been thought to increase the risk of obesity and metabolic syndrome, as well as shorten lifespan. On the other hand, chrono-nutritional studies have shown that time-restricted feeding during active phase significantly suppresses the induction of HFD-induced obesity in mouse model. However, the long-term effects of time-restricted HFD feeding on aging are unknown. Therefore, in this study, we set up a total of four groups: mutual combination of ad libitum feeding or night-time-restricted feeding (NtRF) and an HFD or a control diet. We examined their long-term effects in a senescence-accelerated mouse strain, SAMP8, for over a year. Hearing ability, cognitive function, and other behavioral and physiological indexes were evaluated during the study. Unexpectedly, SAMP8 mice did not show early onset of death caused by the prolonged HFD intake, and both HFD and NtRF retarded age-related hearing loss (AHL). NtRF improved grip strength and cognitive memory scores, while HFD weakly suppressed age-related worsening of the appearance scores associated with the eyes. Notably, the HFD also retarded the progression of AHL in both DBA/2J and C57BL/6J mice. These results suggest that HFD prevents aging unless metabolic disorders occur and that HFD and NtRF are independently effective in retarding aging; thus, the combination of HFD and chrono-nutritional feeding may be an effective anti-aging strategy.

scholarly journals Reversing age-associated arterial dysfunction: insight from preclinical models

2018 ◽  
Vol 125 (6) ◽  
pp. 1860-1870 ◽  
Author(s):  
Venkateswara R. Gogulamudi ◽  
Jinjin Cai ◽  
Lisa A. Lesniewski
Keyword(s):  
Mammalian Target Of Rapamycin ◽  
The United States ◽  
Sirtuin 1 ◽  
Older Individuals ◽  
Beneficial Effects ◽  
Systemic Oxidative Stress ◽  
Age Related ◽  
Energy Sensing ◽  
Primary Risk Factor

Cardiovascular diseases (CVDs) remain the leading causes of death in the United States, and advancing age is a primary risk factor. Impaired endothelium-dependent dilation and increased stiffening of the arteries with aging are independent predictors of CVD. Increased tissue and systemic oxidative stress and inflammation underlie this age-associated arterial dysfunction. Calorie restriction (CR) is the most powerful intervention known to increase life span and improve age-related phenotypes, including arterial dysfunction. However, the translatability of long-term CR to clinical populations is limited, stimulating interest in the pursuit of pharmacological CR mimetics to reproduce the beneficial effects of CR. The energy-sensing pathways, mammalian target of rapamycin, AMPK, and sirtuin-1 have all been implicated in the beneficial effects of CR on longevity and/or physiological function and, as such, have emerged as potential targets for therapeutic intervention as CR mimetics. Although manipulation of each of these pathways has CR-like benefits on arterial function, the magnitude and/or mechanisms can be disparate from that of CR. Nevertheless, targeting these pathways in older individuals may provide some benefits against arterial dysfunction and CVD. The goal of this review is to provide a brief discussion of the mechanisms and pathways underlying age-associated dysfunction in large arteries, explain how these are impacted by CR, and to present the available evidence, suggesting that targets for energy-sensing pathways may act as vascular CR mimetics.

scholarly journals Maternal Resveratrol Supplementation Prevents Cognitive Decline in Senescent Mice Offspring

2019 ◽  
Vol 20 (5) ◽  
pp. 1134 ◽  
Author(s):  
Vanesa Izquierdo ◽  
Verónica Palomera-Ávalos ◽  
Sergio López-Ruiz ◽  
Anna-Maria Canudas ◽  
Mercè Pallàs ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cognitive Decline ◽  
Target Genes ◽  
Epigenetic Inheritance ◽  
Mtor Inhibition ◽  
Beneficial Effects ◽  
Protein Levels ◽  
Age Related ◽  
F2 Generation ◽  
Age Related Cognitive Decline

A variety of environmental factors contribute significantly to age-related cognitive decline and memory impairment in Alzheimer’s Disease (AD) and other neurodegenerative diseases. Nutrition can alter epigenetics, improving health outcomes, which can be transmitted across generations; this process is called epigenetic inheritance. We investigate the beneficial effects of maternal resveratrol supplementation in the direct exposed F1 generation and the transgenerational F2 generation. The offspring was generated from females Senescence Accelerated Mouse-Prone (SAMP8) fed a resveratrol-enriched diet for two months prior to mating. Object novel recognition and Morris Water Maze (MWM) demonstrated improvements in cognition in the 6-month-old F1 and F2 generations from resveratrol fed mothers. A significant increase in global DNA methylation with a decrease in hydroxymethylation in F1 and F2 were found. Accordingly, Dnmt3a/b and Tet2 gene expression changed. Methylation levels of Nrf2 and NF-kβ genes promoters raised in offspring, inducing changes in target genes expression, as well as hydrogen peroxide levels. Offspring that resulted from a resveratrol fed mother showed increase AMPKα activation, mTOR inhibition, and an increase in Pgc-1α gene expression and Beclin-1 protein levels. Endoplasmic reticulum stress sensors were found changed both in F1 and F2 generations. Overall, our results demonstrated that maternal resveratrol supplementation could prevent cognitive impairment in the SAMP8 mice offspring through epigenetic changes and cell signaling pathways.

scholarly journals Eip74EF is a dominant modifier for ALS-FTD linked mutant VCP phenotypes in Drosophila, but not miR-34

2020 ◽  
Author(s):  
Madeleine R. Chalmers ◽  
JiHye Kim ◽  
Nam Chul Kim
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Frontotemporal Dementia ◽  
Genetic Modifier ◽  
Disease Model ◽  
The Other ◽  
Beneficial Effects ◽  
Downstream Target ◽  
Age Related ◽  
Lateral Sclerosis

AbstractIn 2012 Liu et al. reported that miR-34 is an age-related miRNA regulating age-associated events and long-term brain integrity in Drosophila. They demonstrated that modulating miR-34 and its downstream target Eip74EF showed beneficial effects on age-related diseases using a Drosophila model of SCA3trQ78. These results imply that miR-34 could be a general genetic modifier and therapeutic candidate for age-related diseases. Therefore, we examined the effect of miR-34 and Eip74EF on another age-related Drosophila disease model. Using a Drosophila model expressing mutant Drosophila VCP that causes amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), or multisystem proteinopathy (MSP), we demonstrated that abnormal eye phenotypes generated by Drosophila VCP R152H were rescued when expressed with Eip74EF siRNA. Contrary to our expectation, miR-34 overexpression resulted in lethality when expressed with mutant VCP. Our data indicate that the other downstream targets of miR-34 might more significantly interact with mutant VCP, causing lethality. Identifying transcriptional targets of Eip74EF might provide valuable insights into diseases caused by mutations in VCP such as ALS, FTD, and MSP.

scholarly journals γ-Oryzanol Improves Cognitive Function and Modulates Hippocampal Proteome in Mice

Nutrients ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 753 ◽  
Author(s):  
Wiramon Rungratanawanich ◽  
Giovanna Cenini ◽  
Andrea Mastinu ◽  
Marc Sylvester ◽  
Anne Wilkening ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Brain Function ◽  
Clinical Symptoms ◽  
Oryza Sativa L ◽  
Beneficial Effects ◽  
Adult Mice ◽  
Age Related ◽  
Y Maze ◽  
Quantitative Changes

Rice (Oryza sativa L.) is the richest source of γ-oryzanol, a compound endowed with antioxidant and anti-inflammatory properties. γ-Oryzanol has been demonstrated to cross the blood-brain barrier in intact form and exert beneficial effects on brain function. This study aimed to clarify the effects of γ-oryzanol in the hippocampus in terms of cognitive function and protein expression. Adult mice were administered with γ-oryzanol 100 mg/kg or vehicle (control) once a day for 21 consecutive days following which cognitive behavior and hippocampal proteome were investigated. Cognitive tests using novel object recognition and Y-maze showed that long-term consumption of γ-oryzanol improves cognitive function in mice. To investigate the hippocampal proteome modulated by γ-oryzanol, 2D-difference gel electrophoresis (2D-DIGE) was performed. Interestingly, we found that γ-oryzanol modulates quantitative changes of proteins involved in synaptic plasticity and neuronal trafficking, neuroprotection and antioxidant activity, and mitochondria and energy metabolism. These findings suggested γ-oryzanol as a natural compound able to maintain and reinforce brain function. Although more intensive studies are needed, we propose γ-oryzanol as a putative dietary phytochemical for preserving brain reserve, the ability to tolerate age-related changes, thereby preventing clinical symptoms or signs of neurodegenerative diseases.

scholarly journals Peripubertal Stress With Social Support Promotes Resilience in the Face of Aging

Endocrinology ◽  
2016 ◽  
Vol 157 (5) ◽  
pp. 2002-2014 ◽  
Author(s):  
Kathleen E. Morrison ◽  
Sneha Narasimhan ◽  
Ethan Fein ◽  
Tracy L. Bale
Keyword(s):  
Social Support ◽  
Social Interaction ◽  
Reversal Learning ◽  
Myelin Proteins ◽  
Age Related ◽  
Adverse Experiences ◽  
The Face ◽  
Improved Performance ◽  
One Year ◽  
Age Related Cognitive Decline

Abstract The peripubertal period of development is a sensitive window, during which adverse experiences can increase the risk for presentation of cognitive and affective dysfunction throughout the lifespan, especially in women. However, such experiences in the context of a supportive social environment can actually ameliorate this risk, suggesting that resilience can be programmed in early life. Affective disorders and cognitive deficits commonly emerge during aging, with many women reporting increased difficulty with prefrontal cortex (PFC)-dependent executive functions. We have developed a mouse model to examine the interaction between peripubertal experience and age-related changes in cognition and stress regulation. Female mice were exposed to peripubertal chronic stress, during which they were either individually housed or housed with social interaction. One year after this stress experience, mice were examined in tasks to access their cognitive ability and flexibility in stress reactive measures. In a test of spatial memory acquisition and reversal learning where aged females normally display a decreased performance, the females that had experienced stress with social interaction a year earlier showed improved performance in reversal learning, a measure of cognitive flexibility. Because peripuberty is a time of major PFC maturation, we performed transcriptomic and biochemical analysis of the aged PFC, in which long-term changes in microRNA expression and in myelin proteins were found. These data suggest that stress in the context of social support experienced over the pubertal window can promote epigenetic reprogramming in the brain to increase the resilience to age-related cognitive decline in females.

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