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Resveratrol and cognitive function

Resveratrol and cognitive function

Indeed, RESV has funcgion shown to mediate a wide range of biological activities Resveratril extension Resveratrol and cognitive function the life span cofnitive delayed onset Cellulite reduction techniques for arms Exercise and glucose metabolism related diseases 313435 B Cholinergic fiber density in hippocampal CA1 and C dentate gyrus show no effect of resveratrol treatment. Aging 28, — China, School of Basic Medicine, North China University of Science and Technology, Tangshan, HebeiP. The Y-maze scores on day 2 and 3 as well as the slope of the learning curve from day 1 to 3 were used as measures of cognitive functioning. Resveratrol and cognitive function

Cognitive Alternate-day fasting and hunger management is among the most devastating age-related conditions and is rapidly becoming Resvrratrol important cause eRsveratrol disease burdens worldwide.

New strategies Natural energy-boosting wellness tips the funcion and eRsveratrol of cognitive decline Resveratol Natural energy-boosting wellness tips. Resveratrol, a polyphenolic compound, has RResveratrol found to enhance Disinfectant solutions Cellulite reduction techniques for arms cognitivs multiple signaling pathways.

Optimal SIRT1 activation is the most crucial step Cognitivve the neuroprotection cognotive by resveratrol Natural energy-boosting wellness tips cognitive impairment. This review discusses several recent developments in our understanding of functkon mechanisms by which qnd delay age-related anr decline through SIRT1.

Fujction regulatory Resveratrok include Resverafrol, anti-inflammatory, anti-apoptotic processes and autophagy regulation, as well as increases in cerebral wnd flow Resveeatrol improvements in the plasticity Carbohydrates and Heart Health synaptic pathways.

Cognjtive, as well as novel SIRT1 activators, is likely Resverahrol provide promising therapeutic strategies for impeding cognitive decline, repairing brain functions, and supporting healthy aging. This is a preview of cognihive content, cognjtive in via an institution to check access.

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Institutional subscriptions. Abdel-Wahab Snd, Abdel-Wahab Resferatrol Protective ad of resveratrol against chronic intermittent hypoxia-induced spatial memory deficits, hippocampal oxidative DNA damage and increased p47Phox NADPH oxidase Resverztrol in young Diabetic coma and kidney failure. Behav Brain Znd — Article PubMed Resverattol Google Scholar.

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: Resveratrol and cognitive function

Effects of resveratrol on learning and memory in rats with vascular dementia

After perfusion, 18 brains were prepared for electron microscopy de Wilde et al. Semi-thin sections 0. The samples were then coverslipped with DPX and analyzed under a light microscope. Then, nm ultra thin sections were cut of the same blocks and three non-serial sections were collected on mesh copper grids.

Finally, the samples were analyzed and photographs were taken with a Philips TM10 transmission electron microscope. For quantitative analysis, approximately μm 2 tissue surface was scanned systematically in each region, and 61 ± 10 microvascular cross sections were examined in each sample.

Vascular density was calculated for a standard surface area with the help of the sample grid as follows: the number of encountered microvascular profiles was divided by the examined surface area, which was determined by counting the number of grid squares of a standard size provided by the distributor.

Vascular density was then expressed as the number of microvascular profiles on 1 mm 2 surface. In addition to microvessel density, the occurrence of the following features were quantified: luminal endothelial protrusions, large empty endothelial vacuoles and basement membrane thickenings.

The basement membrane was considered thickened when local exfoliations were observed in case of capillaries, or hyalinosis in case of arterioles. The number of microvessels displaying any of the noted abnormalities was counted and expressed as percentage of the total number of microvessels examined.

Capillaries and arterioles were analyzed separately. Since arterioles were encountered at high enough number for statistical analysis only in the hippocampal vascular layer, quantitative analysis of arteriolar condition was performed for this region of the hippocampus only.

Y-maze performance was statistically analyzed with a one way ANOVA paradigm for repeated measures. To evaluate relationships between cerebrovascular parameters and Y-maze performance, a Pearson correlation analysis was applied.

Animals received resveratrol in their food from 1 year of age onwards. Adding resveratrol to the food did not affect food intake, and body weight data not shown. Before behavioral testing started, at the age of 18—20 months, four animals had died 2 CON and 2 RES.

After behavioral testing, but before the end of the experiment at 24 months, nine more animals died 4 CON and 5 RES. There were no significant differences in mortality rate between CON and RES mice, and regular visual inspection did not indicate obvious differences in general health either.

The final level of performance on day 3 and the retention trial on day 10 were not different between CON and RES. Figure 1. Effects of chronic resveratrol supplementation on locomotor behavior in an open field. A Total distance covered during the test.

Figure 2. Effects of chronic resveratrol supplementation on Y-maze learning. The Y-maze test consisted of 3 training days and a retention day 1 week later.

Each day consisted of eight trials and the performance of the animals is expressed as the percentage of correct choices per day. Also, cholinergic fiber density in the CA1 and dentate gyrus of the hippocampus and the PARII region of the cortex was unchanged after RES treatment Figures 3 B—D.

Figure 3. Effects of chronic resveratrol supplementation on the cholinergic system. B Cholinergic fiber density in hippocampal CA1 and C dentate gyrus show no effect of resveratrol treatment. D Cholinergic fiber density in the parietal cortex PARII does not show an effect of resveratrol treatment.

In the parietal cortex, vascular density was not different between the two groups. Figure 4. Effects of chronic resveratrol supplementation on vascular density in the brain. In the hippocampus, resveratrol treatment caused a higher vascular density.

The endothelial cells of cerebral microvessels exhibited two discernible abnormalities. The apical surface of the endothelial cells displayed microvillus-like processes into the lumen Figure 5 A and empty, large vacuoles formed primarily in the vicinity of tight junctions Figure 5 C.

The basement membrane of capillaries occasionally appeared thickened in the form of local exfoliations, while the arteriolar basement membrane, particularly between the endothelial and smooth muscle cells was affected by hyalinosis Figure 5 E.

The occurrence of basement membrane thickening and endothelial processes was not significantly affected by dietary resveratrol Figures 5 B,F. Figure 5. Effects of resveratrol supplementation on the occurrence of microvascular abnormalities.

A Representative photomicrograph and B quantitative analysis of endothelial processes. Arrowheads point at the typical endothelial processes of a cortical capillary. The photomicrograph demonstrates a capillary in the hippocampus CA1 region. Arrowheads are pointing at the large, empty endothelial vacuole.

E Representative photomicrograph and F quantitative analysis of vascular basement membrane thickening. The photomicrograph demonstrates an arteriole in the hippocampal vascular layer. Arrowheads are pointing at healthy and thickened segments of the basement membrane.

To assess whether cognitive functioning in the aged mice was related to their cerebrovascular status, individual Y-maze performance was correlated with vascular parameters.

The Y-maze scores on day 2 and 3 as well as the slope of the learning curve from day 1 to 3 were used as measures of cognitive functioning. Most of these correlations suggest that better learning performance is associated with higher capillary density and lower incidence of vascular abnormalities.

Chronic dietary supplementation with the natural polyphenol resveratrol improved performance of aged mice in the acquisition of a Y-maze task and increased the exploration of the center area of an open-field test. The improvement in cognitive performance as observed in the Y-maze was paralleled by an increased microvascular density in the hippocampus and decreased number of vacuolar abnormalities in both hippocampal and cortical microvascular endothelial cells.

Spatial orientation and memory performance in the Y-maze is at least partly dependent on the hippocampus, a brain area often affected by aging Erickson and Barnes, ; Havekes et al.

We found that resveratrol-treated animals performed better during the acquisition of this task. Although differences in general activity and anxiety are potentially confounding factors in most learning tasks, it is unlikely that this explains the results of the Y-maze test in the present study.

First, during the free exploration in the habituation trial before the start of training, resveratrol-supplemented and control mice showed similar levels of explorative activity in terms of arm visits and spontaneous alternations.

Second, during the training, all animals entered the maze in every trial and latencies were not different for treated versus untreated animals. Furthermore, although the data from the open-field test show an increased exploration in the center of the arena as opposed to the outer rim, it confirms that there was no effect of resveratrol treatment on general locomotor activity, since the total distance covered by animals was the same for both groups.

Taken together, the increased performance of the resveratrol-treated animals during the acquisition phase of the Y-maze task most likely indicates an improved cognitive performance or, alternatively, a reduction in the well-established aging-related decline in cognitive performance Erickson and Barnes, The mechanisms behind resveratrol-induced preservation of cognitive performance during aging are most likely multifactorial.

In the present study improved performance in the resveratrol-supplemented group was paralleled by higher hippocampal microvessel density and less aberrant microvessels in both hippocampus and cortex compared to the control group.

We also tested for associations between Y-maze performance and cerebrovascular parameters on an individual level by means of a correlative analysis. Clearly, this correlative analysis should be interpreted with caution given the high number of possible associations tested and the risk of type-1 statistical errors.

On the other hand, despite the restricted number of animals included in the EM study and the reasonably low variation in the various measures, it is striking that all significant correlations point in the same direction, that is, better performance in the Y-maze was associated with higher capillary density and a lower incidence of vascular abnormalities in either cortex or hippocampus.

These findings thus support the idea that beneficial effects of resveratrol on cognitive function are mediated via the cerebrovascular system. A higher microvascular density and increased cerebral blood flow might improve performance directly by increasing glucose and oxygen supply to relevant brain areas Gold, ; Zlokovic, Additionally, microvessels potentially provide a source of trophic factors such as insulin-like growth factor IGF -1 and nerve growth factor that support neuronal function.

These factors have been shown to decrease in aging together with reductions in cortical microvascular density Sonntag et al. An increased microvascular density can be explained in two ways. Since resveratrol has been reported to inhibit angiogenesis in vitro Igura et al.

Moreover, resveratrol appeared to prevent or delay the occurrence of microvascular abnormalities, another hallmark of aging-related decline in the microvascular condition. There are multiple pathways via which resveratrol could prevent age-related decline in vascular density and occurrence of microvascular abnormalities.

Second, resveratrol is likely to influence cerebrovascular health by its capability to reduce platelet aggregation Bertelli et al. Resveratrol has been categorized as a sirtuin-activating compound which is known to mimic caloric restriction and was found to increase life span in lower organisms via the activation of sir2, a conserved deacetylase proposed to underlie the beneficial effects of caloric restriction Howitz et al.

The finding that caloric restriction itself benefits cortical microvascular density and local cerebral blood flow in aged rats Lynch et al.

Additionally, both resveratrol and SIRT1 were shown to exert vasoprotective effects against oxidative stress and inflammatory factors Csiszar et al. More recent studies found compelling effects of resveratrol, as a substance that potentially enhances the health and lifespan of organisms.

For instance, Barger et al. found that even a low dose of resveratrol partially mimics caloric restriction in mice by assessing transcription patterns in several tissues, including the brain.

Interestingly, chronic resveratrol supplementation in mice on a high-calorie diet showed prolonged survival and a prolonged general health Baur et al. In this particular study, mice received resveratrol in a chronic fashion, doses and timing highly comparable to our experimental design.

The authors found that resveratrol produces changes associated with a longer lifespan, resulting in a physiological shift of middle-aged mice on a high-calorie diet towards that of mice on a standard diet.

In a more recent study by the same group, resveratrol had no effects on survival in normal mice, but they did find that resveratrol mimics transcriptional patterns in different tissues Pearson et al.

Although we did not assess survival, but focused on neurobiological function and cerebrovascular condition, our data suggest that one of the target-systems for resveratrol to exert its beneficial effects can be found in a preservation of the cerebrovascular system.

Interestingly, the effects of resveratrol appear to be the most prominent in the hippocampus as reflected by the region-specific increase in microvascular density.

As an interesting parallel, the beneficial effects of physical exercise on the microvasculature, have also shown a high degree of regional specificity, even within the hippocampal formation Pereira et al.

This demonstrates that, even though the hippocampus is one of the most vulnerable regions when it comes to age-related pathology, the hippocampal microvasculature contains adaptive potential and may prove to be an interesting therapeutic target. In contrast to the results on the cerebrovascular level, we did not find any effects of chronic resveratrol treatment on structural parameters of the cholinergic system i.

cholinergic cell number and fiber density. The lack of effects on neuronal level is actually paralleled by previous studies on aging, where no quantitative difference in the number of neurons or synapses were found for review see Coleman and Flood, A recent study, however, argues in favor of the direct effects of resveratrol on neuronal health since they showed a reduction in neurodegeneration cell death in parallel with a rescued cognitive functioning after resveratrol treatment Kim et al.

However, this study used intracerebroventricular injections which leads to a direct treatment of neuronal tissue. When applied in an oral fashion, resveratrol is required to enter the brain in sufficient levels in order to exhibit its direct effects on neuronal health.

In the present study we show that resveratrol is present in the blood, fluctuating according to daily food intake. However, the bioavailability of resveratrol and relative concentrations in different tissues are still under discussion Rossi et al.

This should be considered when evaluating the relevance of the physiological effects of resveratrol in view of treatment options. In conclusion, this is the first study to show beneficial effects of long-term dietary supplementation with the natural polyphenol resveratrol on cognitive functioning and cerebrovascular condition.

The status of the cerebrovascular system and the neurovascular unit have gained increasing interest as a potential target for treatment of aging associated disorders of the brain Iadecola, ; Zlokovic, In this light, we propose that ingestion of resveratrol, thereby targeting the integrity of the cerebrovascular system, can be an effective and simple method to support healthy aging of the brain.

The research conducted in the paper was financially supported by Danone Research, Centre for Specialised nutrition. Danone Research has a financial interest in the component resveratrol. Eline van der Beek is employed at Danone Research, Centre for Specialised Nutrition in Wageningen, the Netherlands.

Charlotte Oomen, Eszter Farkas, Viktor Roman, Paul Luiten and Peter Meerlo, have no actual or potential conflict of interests concerning the research presented in the paper. We thank Gerrit Witte and Martijn de Wilde at Danone Research for determining resveratrol levels in the blood samples.

We thank Jan Keijser of the Department for Molecular Neurobiology in Haren for his assistance in the Quantimet analysis. Alvira, D. Comparative analysis of the effects of resveratrol in two apoptotic models: inhibition of complex I and potassium deprivation in cerebellar neurons. Neuroscience , — Pubmed Abstract Pubmed Full Text CrossRef Full Text.

Amenta, F. Effect of long-term treatment with the dihydropyridine-type calcium channel blocker darodipine PY on the cerebral capillary network in aged rats. Ageing Dev.

Barger, J. A low dose of dietary resveratrol partially mimics caloric restriction and retards aging parameters in mice. PLoS ONE 3, e Baur, J. Resveratrol improves health and survival of mice on a high-calorie diet.

Nature , — Therapeutic potential of resveratrol: the in vivo evidence. Drug Discov. Bertelli, A. Antiplatelet activity of synthetic and natural resveratrol in red wine. Tissue React. Pubmed Abstract Pubmed Full Text. Buee, L. Acta Neuropathol.

Burns, E. Changes with age in cerebral capillary morphology. Aging 2, — Cao, Z. Cancer Res. Chen, J. SIRT1 protects against microglia-dependent amyloid-beta toxicity through inhibiting NF-kappaB signaling. Coleman, P. Aging 8, — Csiszar, A. Vasoprotective effects of resveratrol and SIRT1: attenuation of cigarette smoke-induced oxidative stress and proinflammatory phenotypic alterations.

Heart Circ. Das, S. Coordinated induction of iNOS-VEGF-KDR-eNOS after resveratrol consumption: a potential mechanism for resveratrol preconditioning of the heart.

De Jong, G. Animal model and postmortem human studies. de Wilde, M. The effect of n-3 polyunsaturated fatty acid-rich diets on cognitive and cerebrovascular parameters in chronic cerebral hypoperfusion.

Brain Res. Dong, W. Resveratrol attenuates ischemic brain damage in the delayed phase after stroke and induces messenger RNA and protein express for angiogenic factors. Erickson, C. The neurobiology of memory changes in normal aging. Farkas, E. Aging 21, — Permanent, bilateral common carotid artery occlusion in the rat: a model for chronic cerebral hypoperfusion-related neurodegenerative diseases.

Farkas, I. Beta-amyloid peptide-induced blood-brain barrier disruption facilitates T-cell entry into the rat brain.

Acta Histochem. Fitzpatrick, D. Endothelium-dependent vasorelaxing activity of wine and other grape products. Frankel, E. Inhibition of human LDL oxidation by resveratrol. Lancet , — Fremont, L. Biological effects of resveratrol. Life Sci. Antioxidant activity of resveratrol and alcohol-free wine polyphenols related to LDL oxidation and polyunsaturated fatty acids.

Gehm, B. Resveratrol, a polyphenolic compound found in grapes and wine, is an agonist for the estrogen receptor. Gold, P. Glucose and age-related changes in memory. Aging 26 Suppl. Havekes, R. Regional differences in hippocampal PKA immunoreactivity after training and reversal training in a spatial Y-maze task.

Hippocampus 17, — Hedreen, J. A modified histochemical technique to visualize acetylcholinesterase-containing axons. Howitz, K. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Iadecola, C. Igura, K. Resveratrol and quercetin inhibit angiogenesis in vitro.

The discrepancy reflects divergent effects of RESV on the juvenile vis-à-vis the aged brain. Administration of RESV in the juvenile age corresponds to a time when the hippocampus was still maturing with very high levels of neurogenesis.

This is in sharp contrast to the current study where RESV was administered at a time when the aged hippocampus was exhibiting a greatly declined neurogenesis, reduced cerebral blood flow, chronic low level inflammation and increased oxidative stress.

It is likely that inflammation, oxidative stress and reduced cerebral blood flow in the aged brain contributed to the reduced neurogenesis and impaired cognitive function and RESV treatment enhanced neurogenesis and microvasculature through antiinflammatory, antioxidant and pro-angiogenic effects, which in turn improved cognitive function in aged rats.

On the other hand, since the juvenile brain does not normally display inflammation, increased oxidative stress or decreased cerebral blood flow, RESV-mediated suppression of normal levels of oxidative stress that are believed to be required for neural stem cell NSC proliferation and differentiation 75 may have impaired neurogenesis and interfered with the cognitive function in juvenile mice.

The observed opposing effects of RESV on the juvenile vis-à-vis the aged brain also imply that RESV treatment can have beneficial effects in a background of a disease state or in conditions such as aging, but may adversely affect function of the developing or the young brain Additional longitudinal studies over the lifespan of animals will be useful to comprehend the mechanisms underlying these differences.

Nonetheless, the beneficial effects of RESV treatment for the aged brain is also apparent from a recent human study, which demonstrated that lower dose of RESV intake for 26 weeks can improve memory performance as well as hippocampus functional connectivity in healthy but overweight older individuals Our results in a rat model of aging provide novel evidence that four weeks of daily RESV treatment in late middle age is efficacious for improving cognitive, memory and mood function in old age.

Additional analyses demonstrated that improved cognitive and mood function following RESV treatment is linked with amelioration of several age-related changes such as decreased neurogenesis and microvasculature and low-level chronic inflammation in the hippocampus. These results suggest that RESV therapy in middle age is beneficial for maintaining normal memory and mood function in old age.

Twenty-one month old male Fischer rats acquired from Harlan Sprague-Dawley Indianapolis, IN, USA were used in this study. All experiments were performed as per the animal protocol approved by the animal studies subcommittee of the Durham Veterans Affairs Medical Center.

Following arrival, animals were allowed to have 7—10 days acclimatization in the vivarium. Figure 1 illustrates the time-line of various treatments and analyses.

Animals with normal spatial learning and memory function were chosen and divided into two groups. The dose of RESV was based on findings in our preliminary studies using middle-aged rats, where this dose increased hippocampal neurogenesis. We chose intraperitoneal injections in this study because we wanted to examine the effects of a relatively lower dose of RESV for a shorter duration 4 weeks.

The drug was injected into areas in the left or right halves of the peritoneal cavity alternatively to minimize repeated injections at one site and peritoneal irritation. Following injections, animals were closely monitored and no writhing behavior was observed.

Thus, animals did not show signs of dermal or peritoneal irritation because of very lower concentration of alcohol used as vehicle in this study.

A month after RESV treatment, a fresh round of WMT was conducted. Following this, the extent of depressive-like behavior was quantified using an FST. In order to determine the production of new cells and the status of hippocampus neurogenesis, stereological quantifications of cells positive for BrdU and DCX were performed for the SGZ-GCL of the DG using serial sections every 10 th immunostained for BrdU or DCX and StereoInvestigator Microbrightfield Inc.

To determine the effects of RESV on other structural changes in different subfields DG, CA1 and CA3 of the hippocampus, we also quantified areas occupied by the microvasculature, astrocytes and microglia through immunohistochemical staining of serial sections every 15th through the hippocampus for RECA-1 a marker of cerebral blood vessels , GFAP a marker astrocytes , OX a marker of microglia and area fraction analyses using J Image.

Moreover, to distinguish any changes in the morphology, we quantified processes of microglia using Neurolucida Microbrightfield. Additionally, to quantify the fraction of microglia that was activated in the vicinity of the neurogenic region, we performed ED-1 immunohistochemistry using serial sections every 15th and quantified the numbers of activated microglia in the DG using StereoInvestigator.

Hippocampus-dependent spatial learning and memory function in aged rats was analyzed using a WMT, as described in our recent studies 77 , The water was rendered opaque by the addition of a white, non-toxic paint and extra-maze cues were positioned on the walls of the room around the tank.

A quartz halogen lamp was positioned aiming at the ceiling to indirectly illuminate the water surface. A video camera was mounted on the ceiling directly above the center of the pool and the movement of rat in the water maze tank was continuously video-tracked and recorded using a computerized ANY-Maze video tracking system Stoelting ANY-maze, Wood Dale, IL, USA.

The rat was trained to find the platform using spatial cues for 7 sessions over 7 days with 4 acquisition trials per session.

Each rat was placed in the water, immediately facing the wall of the tank in one of the quadrants in pseudo-random manner and then allowed a maximal time of 90 seconds to locate the platform with an inter-trial interval of seconds.

Each trial commenced from a different start location. When the subject reached the platform it was allowed to stay there for 30 seconds. When the subject failed to find the platform within the ceiling time of 90 seconds, it was guided onto the platform and allowed to stay there for 30 seconds.

The platform was positioned in the same place across all sessions. Data such as the latency and swim path lengths to reach the platform, swim path efficiency the ratio of the shortest possible swim path length to actual swim path length and swim speed were collected using Anymaze software. Mean latencies to reach the platform were used for assessment of learning curves, as swim speeds did not differ between groups in this study.

A day after the 7-day learning protocol described above, each rat was subjected to a single second probe or memory retrieval test. This involved removal of the platform from the pool and release of rats from the quadrant that is diametrically opposite to the quadrant where the platform was positioned during learning sessions.

Retrieval of learned memory was assessed by comparing dwell time in the PQ with the other three quadrants within the group and also by comparing dwell time in platform quadrant, latency to reach the platform area, dwell time in platform area and platform area crossings across groups.

This test was done as detailed in our recent studies 78 , This ensured that the rat could not touch the bottom of the cylinder with its tail or hind paws or escape from the top.

The rat was subjected to a single session of forced swimming lasting ten minutes. We directly performed the forced swimming trial, as this test was conducted two days after the completion of WMT. Since animals have experienced swimming during learning sessions in the WMT, a separate swimming trial was not given prior to testing in an FST.

Animal behavior during the test was monitored and recorded by a video camera. Investigators scored immobility time for each animal using the recorded videos. Animals that exhibited signs of drowning behavior were quickly removed from the cylinder and excluded for FST analyses.

The amount of time spent in immobility also referred to as floating was calculated later. Immobility is defined as the minimal movement necessary to keep the head above the water level.

Furthermore, we compared FST data in two separate segments 5 minutes each. This is because typically in the first 5 minutes of the test, normal animals i. animals having no depression tend to swim continuously with minimal time spent in immobility in contrast to depressed animals spending greater amount of time in immobility.

In the last 5 minutes of the test, even a normal rat may display increased immobility due to swimming related fatigue.

Therefore, analysis of two segments of FST time helps to dissociate depression-related immobility from fatigue-related immobility. Each animal was first deeply anesthetized with isoflurane in a Plexiglas chamber until it ceased respiration.

Each brain was then mounted on a cryostat chuck and micrometer thick coronal sections through the hippocampus were cut and collected serially in well plates. Two sets of serial sections every 10 th through the entire hippocampus were picked from each animal belonging to RESV and VEH control groups and processed for BrdU and DCX immunostaining, as described in our previous studies 12 , 13 , 82 , Furthermore, additional sets of serial sections every 20 th through the hippocampus were processed for immunohistochemical characterization of cells positive for RECA-1 20 , GFAP 23 , OX 22 and ED-1 The primary antibodies comprised monoclonal antibodies against BrdU , BD Biosciences, San Jose, CA, USA or , Serotech, Raleigh, NC, USA , NeuN , EMD Millipore, Darmstadt, Germany , OX , AbD Serotech , RECA-1 and ED-1 , AbD Serotech and polyclonal antibodies against DCX ; Santa Cruz Biotechnology, Santa Cruz, CA, USA and GFAP , Dako, Carpinteria, CA, USA.

For this, we used micrometer thick serial sections every 10 th for BrdU and DCX and every 20 th for ED-1 analyses through the entire hippocampus and the StereoInvestigator system Microbrightfield comprising a color digital video camera Optronics Inc.

A computer driven motorized stage then allowed the cells to be measured at each of the counting frame locations. This plane served as the first point of the counting process.

This procedure was repeated for all serial sections. By utilizing parameters such as the initial section thickness i. at the time of sectioning , the section thickness at the time of cell counting i.

The Gundersen coefficient error CE was in the range of 0. The sections processed for BrdU and NeuN dual immunofluorescence were analyzed using a laser scanning confocal microscope FVi, Olympus , as described in our earlier reports In brief, microscopic images from different regions of the hippocampus were digitized using 20× objective lens in a Nikon E microscope equipped with a digital video camera connected to a computer.

The overall morphology of microglia were compared between RESV and VEH treated groups by measuring processes of randomly selected but well stained OX microglial cells from both groups. These measurements were made using a semiautomatic neuron tracing system Neurolucida; Microbrightfield linked to a Nikon microscope.

To measure the extent of process growth away from the soma and the branching of processes at different distances from the soma, the concentric circle analysis of Sholl was performed using NeuroExplorer component of the Neurolucida program. A semiautomatic tracing system Neurolucida, Microbrightfield linked to a Nikon microscope was employed for these measurements.

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This study was supported by grants from the National Institutes of Health National Center for Complementary and Alternative Medicine R21 award, AT to AKS , State of Texas Emerging Technology Funds to AKS and Department of Veterans Affairs VA Merit Award to AKS.

Present address: Department of Radiation Oncology, Univ California Irvine,. Research Service, Olin E. Teague Veterans Affairs Medical Center, Central Texas Veterans Health Care System, Temple, Texas, USA.

Department of Surgery Neurosurgery and Research Service, Duke University and Veterans' Affairs Medical Centers, Durham, North Carolina, USA. Vipan K. You can also search for this author in PubMed Google Scholar.

and V. contributed equally to this work. performed statistical analyses of behavioral tests, stereological cell counts, immunohistochemistry, J imaging and Neurolucida tracing to quantify cognitive and mood function, hippocampus neurogenesis, microvasculature and microglia, prepared figure composites and the first version of the manuscript text.

performed water maze and forced swim tests, administration of resveratrol, initial analyses of behavioral data and some experiments for neuronal differentiation of newly born cells.

contributed to the experimental design, analyses and interpretation of behavioral data, analyses of neuronal differentiation of newly born cells using confocal microscopy, immunohistochemistry, photomicrography and preparation of composite figures. performed GFAP immunohistochemistry, J Imaging of astrocytes and the associated statistical analyses.

performed animal perfusions, tissue processing, cryostat sectioning, histology and BrdU and DCX immunohistochemistry. conceived the study, conceptualized the research design, interpreted all behavioral and immunohistochemical results and prepared the final version of manuscript text and figures.

All authors gave input to the manuscript text and approved the final version of the manuscript. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.

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Resveratrol may contribute to brain ageing reversal by as much as ten years: Study

Another study found that 75mg resveratrol, the lowest dose tested, was the most efficacious dose to acutely elicit global cerebral vasodilatation and improve performance of a sustained attention task in type 2 diabetes patients.

Results of the RESHAW Resveratrol Supporting Healthy Aging in Women clinical study found that compared to placebo, resveratrol improved overall cognitive performance, whilst weakening the decline in cerebrovascular responsiveness CVR to cognitive stimuli.

The latter effect was associated with reduction of fasting blood glucose. The study concludes that taking this evidence into account, the team think the improvements in resting BFV and PI with resveratrol highlights the ability of regular resveratrol supplementation to sustain cerebrovascular function, which may, in turn, preserve cognitive function in elderly women.

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Download references. AFSF, PC and KBG offer thanks to the Conselho Nacional de Desenvolvimento Científico e Tecnológico CNPq , Brazil for the research grants. JAGT offers her thanks to the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior CAPES , Brazil for the research grant.

Department of Clinical and Toxicological Analyses, School of Pharmacy, Federal University of Minas Gerais, Presidente Antônio Carlos Avenue, , Pampulha, Belo Horizonte, Minas Gerais, , Brazil.

Department of Medical Clinical, School of Medicine, Federal University of Minas Gerais, Professor Alfredo Balena Avenue, , Belo Horizonte, Minas Gerais, , Brazil. You can also search for this author in PubMed Google Scholar. Correspondence to Karina Braga Gomes. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

AFSF, JAGT and KBG designed and conducted the study. AFSF, JAGT and KBG analyzed the data. AFSF, JAGT, KBG and PC wrote, revised the article, and approved the final version of the manuscript.

Reprints and permissions. Tosatti, J. et al. Effects of Resveratrol Supplementation on the Cognitive Function of Patients with Alzheimer's Disease: A Systematic Review of Randomized Controlled Trials.

Drugs Aging 39 , — Download citation. Accepted : 02 February Published : 21 February Issue Date : April Anyone you share the following link with will be able to read this content:.

Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. Objectives The aim of this systematic review was to investigate the evidence in the published literature from studies that evaluated the effects of supplementation with resveratrol, alone or in a solution with glucose and malate RGM , on the functional and cognitive performance of patients with AD, as assessed by validated instruments.

Methods A systematic literature search was performed in MEDLINE, CENTRAL, Embase, CINAHL, Web of Science, and Scopus databases including articles published up to August

Resveratrol may reverse cognitive ageing by ten years J Biol Chem 17 — Article PubMed CAS Google Scholar Sun AY, Wang Q, Simonyi A, Sun GY Botanical phenolics and brain health. Neurodegener Dis 9 4 — Article PubMed CAS Google Scholar Skaper SD, Facci L, Giusti P Neuroinflammation, microglia and mast cells in the pathophysiology of neurocognitive disorders: a review. To examine cognitive performance, the mice were subjected to a Y-maze test in which they had to learn the location of a food reward in one of two accessible choice arms Havekes et al. In contrast, with RESV treatment, aged rats showed an improved ability for both spatial learning and spatial memory during this period. Eline van der Beek is employed at Danone Research, Centre for Specialised Nutrition in Wageningen, the Netherlands. On the other hand, memory and mood dysfunction in old age has been linked strongly to decreased function of DG in the hippocampus 3 , 4.
Resveratrol Cellulite reduction techniques for arms a neuroprotective Cognitivd acting in Antioxidant rich smoothies prevention of redox impairment in addition Resveratrok exerting anti-apoptotic actions on brain cells. Triathlon nutrition periodization ability to reduce neuronal damage in patients with AD Natural energy-boosting wellness tips been suggested fubction preclinical studies. The aim of functiln Natural energy-boosting wellness tips review was funcyion investigate the evidence in the published literature from studies that evaluated the effects of supplementation with resveratrol, alone or in a solution with glucose and malate RGMon the functional and cognitive performance of patients with AD, as assessed by validated instruments. A systematic literature search was performed in MEDLINE, CENTRAL, Embase, CINAHL, Web of Science, and Scopus databases including articles published up to August Randomized, placebo-controlled, clinical trials that reported cognitive and functional performance, as measured by the Alzheimer's Disease Assessment Scale—Cognitive Subscale ADAS-cogCooperative Study of Alzheimer's Disease—Activities of Daily Living ADCS-ADLor the Mini Mental State Examination MMSEin AD patients treated with resveratrol, alone or as RGM, were included.

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