scholarly journals A Walnut-enriched Diet and Physical Activity Enhanced Cognitive and Motor Function in Aged Mice (P14-010-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Carsten Esselun ◽  
Benjamin Dilberger ◽  
Carmina Silaidos ◽  
Gunter Eckert
Keyword(s):  
Physical Activity ◽  
Spatial Memory ◽  
Motor Function ◽  
Mitochondrial Function ◽  
Brain Aging ◽  
Enriched Environment ◽  
Motor Functions ◽  
Nmri Mice ◽  
Aged Mice ◽  
Y Maze

Abstract Objectives This study aims to investigate walnut's effect alone and in combination with an enriched environment on brain aging of aged NMRI mice by investigation of cognition and motor functions. Furthermore, it aims to identify the underlying mechanisms by evaluating the expression of relevant genes. Methods NMRI mice (12mo.) were fed with a 6% walnut-enriched diet (WED) or control diet respectively, for the duration of 6 months. Additionally, one WED group was exposed to an enriched environment. Cognition and motor functions were assessed to evaluate walnut's effect on spatial memory, general physical activity and motor coordination. Conducted tests included Y-Maze alternation, open field and rotarod. Expression levels of relevant genes including synaptophysin, NGF and BDNF were measured via qPCR in brain tissue. Mitochondrial function was investigated by testing for ATP levels and mitochondrial membrane potential in dissociated brain cells and oxygen consumption of the oxidative phosphorylation system of freshly isolated mitochondria. Results Intake of the walnut diet significantly increased the alternation rate in a Y-Maze experiment (P < 0.05). Physical activity did not further improve this effect on spatial memory of mice, but increased mice’ activity (P < 0.001) in general. Motor function in rotarod test was not improved by walnut intake alone, but significantly increased by added enrichment (P < 0.01). Gene expression of synaptophysin was significantly increased for walnuts alone (P < 0.05), while BDNF and NGF expression appeared to be unaffected. Additional enriched environment resulted in a trend for these genes to be increased as well. Results imply that mitochondrial function is not linked to these improvements. Conclusions Long term walnut diet significantly improved cognitive function in aged mice. Physical activity additionally improved motor functions. These benefits could possibly be explained by increased expression of genes involved in neuronal plasticity. Funding Sources Grant from California Walnut Commission.

scholarly journals Cerebral Mitochondrial Function and Cognitive Performance during Aging: A Longitudinal Study in NMRI Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Martina Reutzel ◽  
Rekha Grewal ◽  
Benjamin Dilberger ◽  
Carmina Silaidos ◽  
Aljoscha Joppe ◽  
...  
Keyword(s):  
Longitudinal Data ◽  
Cognitive Performance ◽  
Mitochondrial Biogenesis ◽  
Mitochondrial Function ◽  
Aging Process ◽  
Brain Aging ◽  
Model Organisms ◽  
Nmri Mice ◽  
Aged Mice ◽  
The Brain

Brain aging is one of the major risk factors for the development of several neurodegenerative diseases. Therefore, mitochondrial dysfunction plays an important role in processes of both, brain aging and neurodegeneration. Aged mice including NMRI mice are established model organisms to study physiological and molecular mechanisms of brain aging. However, longitudinal data evaluated in one cohort are rare but are important to understand the aging process of the brain throughout life, especially since pathological changes early in life might pave the way to neurodegeneration in advanced age. To assess the longitudinal course of brain aging, we used a cohort of female NMRI mice and measured brain mitochondrial function, cognitive performance, and molecular markers every 6 months until mice reached the age of 24 months. Furthermore, we measured citrate synthase activity and respiration of isolated brain mitochondria. Mice at the age of three months served as young controls. At six months of age, mitochondria-related genes (complex IV, creb-1, β-AMPK, and Tfam) were significantly elevated. Brain ATP levels were significantly reduced at an age of 18 months while mitochondria respiration was already reduced in middle-aged mice which is in accordance with the monitored impairments in cognitive tests. mRNA expression of genes involved in mitochondrial biogenesis (cAMP response element-binding protein 1 (creb-1), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1-α), nuclear respiratory factor-1 (Nrf-1), mitochondrial transcription factor A (Tfam), growth-associated protein 43 (GAP43), and synaptophysin 1 (SYP1)) and the antioxidative defense system (catalase (Cat) and superoxide dismutase 2 (SOD2)) was measured and showed significantly decreased expression patterns in the brain starting at an age of 18 months. BDNF expression reached, a maximum after 6 months. On the basis of longitudinal data, our results demonstrate a close connection between the age-related decline of cognitive performance, energy metabolism, and mitochondrial biogenesis during the physiological brain aging process.

scholarly journals A Walnut Diet in Combination with Enriched Environment Improves Cognitive Function and Affects Lipid Metabolites in Brain and Liver of Aged NMRI Mice

2020 ◽  
Author(s):  
Carsten Esselun ◽  
Benjamin Dilberger ◽  
Carmina V. Silaidos ◽  
Elisabeth Koch ◽  
Nils Helge Schebb ◽  
...  
Keyword(s):  
Physical Activity ◽  
Synaptic Plasticity ◽  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Function ◽  
Mitochondrial Respiration ◽  
Mitochondrial Membrane ◽  
Nmri Mice ◽  
Y Maze ◽  
The Brain

AbstractThis in vivo study aimed to test if a diet enriched with 6% walnuts alone or in combination with physical activity supports healthy ageing by changing the oxylipin profile in brain and liver, improving motor function, cognition, and cerebral mitochondrial function. Female NMRI mice were fed a 6% walnut diet starting at an age of 12 months for 24 weeks. One group was additionally maintained in an enriched environment, one group without intervention served as control. After three months, one additional control group of young mice (3 weeks old) was introduced. Motor and cognitive functions were measured using Open Field, Y-Maze, Rotarod and Passive Avoidance tests. Lipid metabolite profiles were determined using RP-LC-ESI(-)-MS/MS in brain and liver tissues of mice. Cerebral mitochondrial function was characterized by the determination of ATP levels, mitochondrial membrane potential and mitochondrial respiration. Expression of genes involved with mito- and neurogenesis, inflammation, and synaptic plasticity were determined using qRT-PCR. A 6% walnut-enriched diet alone improved spatial memory in a Y-Maze alternation test (p < 0.05) in mice. Additional physical enrichment enhanced the significance, although the overall benefit was virtually identical. Instead, physical enrichment improved motor performance in a Rotarod experiment (p* < 0.05) which was unaffected by walnuts alone. Bioactive oxylipins like hydroxy-polyunsaturated fatty acids (OH-PUFA) derived from linoleic acid (LA) were significantly increased in brain (p** < 0.01) and liver (p*** < 0.0001) compared to control mice, while OH-PUFA of α-linolenic acid (ALA) could only be detected in the brains of mice fed with walnuts. In the brain, walnuts combined with physical activity reduced arachidonic acid (ARA)-based oxylipin levels (p < 0.05). Effects of walnut lipids were not linked to mitochondrial function, as ATP production, mitochondrial membrane potential and mitochondrial respiration were unaffected. Furthermore, common markers for synaptic plasticity and neuronal growth, key genes in the regulation of cytoprotective response to oxidative stress and neuronal growth were unaffected. Taken together, walnuts change the oxylipin profile in liver and brain, which could have beneficial effects for healthy ageing, an effect that can be further enhanced with an active lifestyle. Further studies may focus on specific nutrient lipids that potentially provide preventive effects in the brain.

scholarly journals Effects of Long-Term Treatment with a Blend of Highly Purified Olive Secoiridoids on Cognition and Brain ATP Levels in Aged NMRI Mice

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Martina Reutzel ◽  
Rekha Grewal ◽  
Carmina Silaidos ◽  
Jens Zotzel ◽  
Stefan Marx ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Citrate Synthase ◽  
Brain Aging ◽  
Mrna Levels ◽  
Nmri Mice ◽  
Aged Mice ◽  
Atp Levels ◽  
Long Term Treatment ◽  
The Brain

Aging represents a major risk factor for developing neurodegenerative diseases such as Alzheimer’s disease (AD). As components of the Mediterranean diet, olive polyphenols may play a crucial role in the prevention of AD. Since mitochondrial dysfunction acts as a final pathway in both brain aging and AD, respectively, the effects of a mixture of highly purified olive secoiridoids were tested on cognition and ATP levels in a commonly used mouse model for brain aging. Over 6 months, female NMRI mice (12 months of age) were fed with a blend containing highly purified olive secoiridoids (POS) including oleuropein, hydroxytyrosol and oleurosid standardized for 50 mg oleuropein/kg diet (equivalent to 13.75 mg POS/kg b.w.) or the study diet without POS as control. Mice aged 3 months served as young controls. Behavioral tests showed deficits in cognition in aged mice. Levels of ATP and mRNA levels of NADH-reductase, cytochrome-c-oxidase, and citrate synthase were significantly reduced in the brains of aged mice indicating mitochondrial dysfunction. Moreover, gene expression of Sirt1, CREB, Gap43, and GPx-1 was significantly reduced in the brain tissue of aged mice. POS-fed mice showed improved spatial working memory. Furthermore, POS restored brain ATP levels in aged mice which were significantly increased. Our results show that a diet rich in purified olive polyphenols has positive long-term effects on cognition and energy metabolism in the brain of aged mice.

scholarly journals A Walnut-Enriched Diet Modifies the Oxylipin Profile in Liver and Brain of Aged Mice — Impact on Inflammation Markers

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1203-1203
Author(s):  
Gunter Eckert ◽  
Gunter Esselun ◽  
Elisabeth Koch ◽  
Nils Schebb
Keyword(s):  
Physical Activity ◽  
Fatty Acids ◽  
Brain Aging ◽  
Inflammatory Marker ◽  
Inflammation Markers ◽  
Aged Mice ◽  
Funding Sources ◽  
Age Related ◽  
The Brain ◽  
Related Increase

Abstract Objectives Neuroinflammation contributes to brain-aging which may be mitigated by anti-inflammatory oxylipins. Based on our previous findings that a 6% walnut-enriched diet alone, and additional physical activity (PA), enhanced cognition in 18 months old NMRI, we now investigated the effects of this diet on oxylipin- and inflammatory marker levels in liver and brain. Methods 18 months and 3 months old female NMRI mice were fed with a 6% walnut-enriched diet. Oxylipins were determined in brain and liver sections using LC-MS. Expression of IL1β gene was determined by qRT-PCR. Results The walnut diet compensates for the age related increase in IL1β gene expression in the liver of mice, whereas expression in the brain was not affected. Basal levels of oxylipins in brain and liver samples isolated from young mice were generally lower compared to aged mice. The walnut diet further increased oxylipin levels of walnut specific fatty acids in liver and brain of aged mice. Enrichment of linoleic acid (LA) and α-linolenic acid (ALA) derived oxylipin levels were quantitatively higher in the liver compared to the brain (P &lt; 0.0001). Hydroxy-oxylipins (HO) based on fatty acid LA were significantly increased in brain (P &lt; 0.001) and liver (P &lt; 0.0001) compared to control mice, while ALA based HO were only detected in the brains of walnut fed mice. The walnut diet in combination with physical activity (PA) reduced ARA based oxylipin levels (P &lt; 0.05). Across all groups, concentrations of prostanoids were higher in the brain as compared to liver (P &lt; 0.001). In the liver, walnuts tended to decrease PGD2 and TxB2 levels while increasing 6-keto PGF1α. The latter, as well as TxB2 tended to be decreased in the brain. Other ARA based prostanoids were unaffected. Effects of PA were contrary to each other, tending to increase ARA based prostanoids in the liver while decreasing them in the brain. PA further enhanced this effect in the brain, but tended to increase the inflammatory response in the liver. Conclusions A walnut diet differentially affects the oxylipin profile of liver and brain in aged mice. Production of oxylipins based on walnut fatty acids is generally increased. Attenuation of age-related, chronic inflammation in might be one of walnut's benefits and may contribute to a healthier aging of the brain. Funding Sources Research was supported by grants from California Walnut Commission.

scholarly journals Enriched environment and masticatory activity rehabilitation recover spatial memory decline in aged mice

2013 ◽  
Vol 14 (1) ◽  
pp. 63 ◽  
Author(s):  
Fabíola de Carvalho Chaves de Siqueira Mendes ◽  
Marina Negrão de Almeida ◽  
André Pinheiro Felício ◽  
Ana Fadel ◽  
Diego de Silva ◽  
...  
Keyword(s):  
Spatial Memory ◽  
Enriched Environment ◽  
Memory Decline ◽  
Aged Mice

Effects of Exercise Interventions on Habitual Physical Activity and Sedentary Behavior in Adolescents With Cerebral Palsy

2019 ◽  
Vol 31 (4) ◽  
pp. 416-424 ◽  
Author(s):  
Simona Bar-Haim ◽  
Ronit Aviram ◽  
Anat Shkedy Rabani ◽  
Akram Amro ◽  
Ibtisam Nammourah ◽  
...  
Keyword(s):  
Physical Activity ◽  
Cerebral Palsy ◽  
Resistance Training ◽  
Sedentary Behavior ◽  
Motor Function ◽  
Classification System ◽  
Habitual Physical Activity ◽  
Progressive Resistance Training ◽  
Exercise Interventions ◽  
Progressive Resistance

Purpose:Exercise interventions have been shown to increase motor capacities in adolescents with cerebral palsy; however, how they affect habitual physical activity (HPA) and sedentary behavior is unclear. The main objective was to correlate changes in HPA with changes in mobility capacity following exercise interventions.Methods:A total of 54 participants (aged 12–20 y) with bilateral spastic cerebral palsy at Gross Motor Function Classification System (GMFCS) levels II and III received 4 months of group progressive resistance training or treadmill training. Mobility measurements and HPA (averaged over 96 h) were made before and after interventions.Results:Averaged baseline mobility and HPA measures and improvements in each after both interventions were positively correlated in all participants. Percentage of sedentary/awake time decreased 2%, with significant increases in HPA measures of step count (16%), walk time (14%), and upright time (9%). Mobility measures and HPA changes were quite similar between Gross Motor Function Classification System levels, but improvement in HPA after group progressive resistance training was greater than after treadmill training (12% vs 4%) and correlated with mobility improvement.Conclusions:Mobility capacity improved after these interventions and was clearly associated with improved HPA. The group progressive resistance training intervention seems preferable to improve HPA, perhaps related to greater social interaction and motivation provided by group training.

scholarly journals Short-Term and Long-Term Effects of Riding for Children with Cerebral Palsy Gross Motor Functions

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
L. Žalienė ◽  
D. Mockevičienė ◽  
B. Kreivinienė ◽  
A. Razbadauskas ◽  
Ž. Kleiva ◽  
...  
Keyword(s):  
Cerebral Palsy ◽  
Motor Function ◽  
Long Term Effects ◽  
Short Term ◽  
Gross Motor ◽  
Motor Functions ◽  
Gross Motor Skills ◽  
Gross Motor Function ◽  
Group I

Aim. To evaluate the effects of riding for beginners (short-term) and advanced (long-term) riders with cerebral palsy on their whole mobility. The study involved 15 subjects (two girls and eleven boys). The subjects were aged from 3 to 19 years (8.73 years ± 5.85). All of the subjects had been diagnosed with a spastic form of cerebral palsy. The duration of the participation differed as follows: the advanced subjects had been riding for 1-4 years (2.66 years ± 1.16), while the beginners have been riding for two weeks (10 sessions). Group I (advanced riders) consisted of eight subjects (7 boys and 1 girl) who had therapy sessions regularly once a week and differed only in terms of the duration of their participation in the experiment. Group II (beginners) consisted of seven children (1 girl and 6 boys) who participated in only 10 riding sessions. All of the subjects were assessed according to the Gross Motor Function Measure (GMFM) and Gross Motor Function Classification System for CP (GMFCS) both before the investigation and after it. Conclusions. Ten riding lessons did not have an influence on the beginner riders with cerebral palsy gross motor functions and their gross motor function level did not change. However, in half of the advanced riders with cerebral palsy, the gross motor functions significantly improved. Meanwhile, the level of the performance of the gross motor skills in the four advanced riders increased, but this difference was not statistically significant.

Neuroprotection and Enhancement of Spatial Memory by Herbal Mixture HT008-1 in Rat Global Brain Ischemia Model

2008 ◽  
Vol 36 (02) ◽  
pp. 287-299 ◽  
Author(s):  
Yun Tai Kim ◽  
Youn-Ju Yi ◽  
Mi-Yeon Kim ◽  
Youngmin Bu ◽  
Zhen Hua Jin ◽  
...  
Keyword(s):  
Spatial Memory ◽  
Brain Ischemia ◽  
Neuronal Damage ◽  
Memory Function ◽  
Neuronal Cell ◽  
Memory Deficit ◽  
Global Brain Ischemia ◽  
Herbal Mixture ◽  
Y Maze ◽  
Global Brain

To investigate whether HT008-1, a prescription used in traditional Korean medicine to treat mental and physical weakness, has a neuroprotective effect on a rat model of global brain ischemia and an enhancing effect against memory deficit following ischemia. Global brain ischemia was induced for 10 min by using 4-vessel occlusion (4-VO). HT008-1 was orally administered at doses of 30, 100, and 300 mg/kg respectively twice at 0 and 90 min after ischemia. The effect on memory deficit was investigated by using a Y-maze neurobehavioral test 4 days after brain ischemia, and the effect on neuronal damage was measured 7 days after ischemia. The mechanism of action was studied immunohistochemically using an anti-CD11b (OX-42) antibody. The oral administration of HT008-1 at 100 and 300 mg/kg significantly reduced hippocampal neuronal cell death by 49% and 53%, respectively, compared with a vehicle-treated group, and also improved spatial memory function in the Y-maze test. Immunohistochemically, HT008-1 inhibited OX-42 expression in the hippocampus. The effects of HT008-1 were more pronounced than those of its individual herb components. The herbal mixture HT008-1 protects the most vulnerable CA1 pyramidal cells of the hippocampus and enhances spatial memory function against global brain ischemia; an anti-inflammatory effect may be one of the mechanisms of action.

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