Mitigating Age-Related Cognitive Decline and Oxidative Status in Rats Treated with Catechin and Polyphenon-60.

Aging is a normal physiological process influenced by the combination of multiple mechanisms, primarily oxidative stress and neuroinflammation, which impact general physiology and brain function. Phenolic compounds have demonstrated the ability to slow down the aging process of the brain due to their antioxidant and anti-inflammatory effects. This study assessed the protective properties of catechin and polyphenon-60 in non-pathologically aged rats regarding visuo-spatial learning and the oxidative status of the frontal cortex. Old animals were treated with catechin or green tea extract (polyphenon-60) for 36 days, daily. Healthy old and young rats were used as controls. During the first training phase, treated rats executed the test better, locating the target in less time compared with the controls. Biomarkers of oxidative stress (catalase activities, superoxide dismutase, glutathione reductase, and glutathione S-transferase) were reduced in the brain of old animals, although their activities were partially improved after both antioxidant treatments. Furthermore, the rise in the production of reactive oxygen species and malondialdehyde levels-a marker of lipid peroxidation-in the frontal cortex of aged animals was significantly ameliorated after the interventions. In conclusion, old rats exhibited enhanced cognitive function and reduced stress levels following the administration of catechin and polyphenon-60.

Impact of Gut Microbiota in Brain Ageing: Polyphenols as Beneficial Modulators.

Brain ageing is a complex physiological process that includes several mechanisms. It is characterized by neuronal/glial dysfunction, alterations in brain vasculature and barriers, and the decline in brain repair systems. These disorders are triggered by an increase in oxidative stress and a proinflammatory state, without adequate antioxidant and anti-inflammatory systems, as it occurs in young life stages. This state is known as inflammaging. Gut microbiota and the gut-brain axis (GBA) have been associated with brain function, in a bidirectional communication that can cause loss or gain of the brain's functionality. There are also intrinsic and extrinsic factors with the ability to modulate this connection. Among the extrinsic factors, the components of diet, principally natural components such as polyphenols, are the most reported. The beneficial effects of polyphenols in brain ageing have been described, mainly due to their antioxidants and anti-inflammatory properties, including the modulation of gut microbiota and the GBA. The aim of this review was, by following the canonical methodology for a state-of-the-art review, to compose the existing evidenced picture of the impact of the gut microbiota on ageing and their modulation by polyphenols as beneficial molecules against brain ageing.

Neurochemical and Cognitive Beneficial Effects of Moderate Physical Activity and Catechin in Aged Rats.

A healthy aging process is a requirement for good life quality. A relationship between physical activity, the consumption of antioxidants and brain health has been stablished via the activation of pathways that reduce the harmful effects of oxidative stress, by inducing enzymes such as SIRT1, which is a protector of brain function. We analyzed the cognitive and neurochemical effects of applying physical exercise in elderly rats, alone or in combination with the antioxidant catechin. Several tests of spatial and episodic memory and motor coordination were evaluated. In addition, brain monoaminergic neurotransmitters and SIRT1 protein levels were assessed in the brains of the same rats. The results show that physical activity by itself improved age-related memory and learning deficits, correlating with the restoration of brain monoaminergic neurotransmitters and SIRT1 protein levels in the hippocampus. The administration of the antioxidant catechin along with the exercise program enhanced further the monoaminergic pathways, but not the other parameters studied. These results agree with previous reports revealing a neuroprotective effect of physical activity, probably based on its ability to improve the redox status of the brain, demonstrating that exercise at an advanced age, combined with the consumption of antioxidants, could produce favorable effects in terms of brain health.

Cognitive and Neurochemical Changes Following Polyphenol-Enriched Diet in Rats.

Dietary recommendations are frequently developed based on nutrient deficiency or prevention of disease, but less attention has been paid to the dietary guidelines to promote brain health. Active and healthy aging is a prerequisite for improving quality of life as people age, and evidence is establishing a relationship between diet and brain health. This work studied the effect of a diet based on foods rich in antioxidants, especially polyphenols, in rats, three days a week for 20 months starting at 14 months. Behavioral analysis testing working memory, spatial and episodic memory, as well as brain monoaminergic neurotransmitters involved in these processes but also in general brain health were analyzed. In addition, hippocampal SIRT1 protein which has an important role in regulating normal brain function was evaluated. The results show that long-term intake of polyphenol-enriched diet improves memory and learning, correlating with restoration of brain monoaminergic neurotransmitters and hippocampal SIRT1 levels in aged rats. These results agree with reports revealing a neuroprotective effect of different polyphenolic compounds on age-related brain decline, based on its antioxidant and anti-inflammatory properties; and demonstrate that consumption of antioxidant-rich foods, a few days a week, gives good long-term results in terms of brain health.

Chronic Polyphenon-60 or Catechin Treatments Increase Brain Monoamines Syntheses and Hippocampal SIRT1 Levels Improving Cognition in Aged Rats.

Polyphenolic compounds from green tea have great interest due to its large consumption and therapeutic potential on the age-associated brain decline. The current work compares a similar dose regimen of a whole-green-tea extract and catechin in old rats over the course of 36 days. Results showed a significant improvement in visuo-spatial working memory and episodic memory of old rats after polyphenolic compounds administration assessed by behavioral tests. No effects were observed on the age-associated motor coordination decline. Statistically, results were correlated with significant improvements, mainly in hippocampal and striatal noradrenergic and serotonergic systems, but also with the striatal dopaminergic system. Both polyphenolic treatments also reverted the age-associated reduction of the neuroinflammation by modulating protein sirtuin 1 (SIRT1) expression in hippocampus, but no effects were observed in the usual reduction of the histone-binding protein RBAP46/48 protein linked to aging. These results are in line with previous ones obtained with other polyphenolic compounds, suggesting a general protective effect of all these compounds on the age-associated brain decline, pointing to a reduction of the oxidative stress and neuroinflammatory status reduction as the leading mechanisms. Results also reinforce the relevance of SIRT1-mediated mechanism on the neuroprotective effect and rule out the participation of RBAP46/48 protein.

Improved age-related deficits in cognitive performance and affective-like behavior following acute, but not repeated, 8-OH-DPAT treatments in rats: regulation of hippocampal FADD.

The aims of this study were (1) to behaviorally phenotype rats at different ages for both cognitive performance and affect, (2) to evaluate the possible beneficial effects of 8-OH-DPAT (a 5-HT1A receptor agonist) treatments on improving age-related behavioral deficits, and (3) to uncover putative key brain targets (e.g., Fas-associated protein with death domain [FADD] and related partners) that might contribute to the observed age-related behavioral changes. The principal results showed that acute, but not repeated, 8-OH-DPAT treatments improved age-related deficits in cognitive performance and affect while induced hypothermia. Moreover, multifunctional FADD protein decreased with age specifically in the hippocampus (as compared to the prefrontal cortex) and was further decreased following acute 8-OH-DPAT. The major conclusions indicate a parallelism between the beneficial effects observed following acute 8-OH-DPAT on improving the negative consequences of aging on cognition and affect, together with the acute induction of hypothermia and hippocampal FADD regulation. Because these effects were not observed following repeated treatment (i.e., observed tolerance to acute hypothermia), the results suggest 5-HT1A receptors desensitization and/or the activation of compensatory adaptive mechanisms.

Repeated treatment with the α2-adrenoceptor agonist UK-14304 improves cognitive performance in middle-age rats: Role of hippocampal Fas-associated death domain.

The cell fate regulator Fas-associated death domain (FADD) balances cell death with non-apoptotic actions via its phosphorylated form. A recent study associated loss of cortical FADD with cognitive decline and increased risk of clinical dementia. Since the activation of cortical α2A-adrenoceptors improved memory deficits in various animal models of working memory loss, the present study evaluated whether UK-14304, an α2-adrenoceptor agonist known to acutely regulate brain FADD forms, would improve cognitive function in middle-aged rats. Sprague-Dawley rats were treated with UK-14304 (0.3 or 1 mg/kg) or saline (1 mL/kg) for seven days. Cognitive performance was evaluated in the eight-arm radial maze. FADD protein content was measured in the prefrontal cortex and hippocampus by Western blot analysis. The results showed that UK-14304 (1 mg/kg) improved cognitive performance (less time: -310±45 s, p=0.025 and fewer errors: -2.75±1.06, p=0.043 to complete the maze) and increased FADD selectively in the hippocampus (+35±11%, p=0.029). Interestingly, hippocampal FADD content negatively correlated with the time ( r=-0.651, p<0.01) needed to complete the maze. Thus, better cognitive scores were associated with higher FADD hippocampal content. These results support a role for α2-adrenoceptors in ameliorating cognition and suggest FADD protein content as a possible correlate for cognitive performance.

Effects of Resveratrol and Other Polyphenols on the Most Common Brain Age-Related Diseases.

BACKGROUND: With global increase in elderly population, modern societies must find strategies to reduce the consequences of aging process; thereby decreasing the incidence of age-related neurodegenerative diseases. Oxidative stress and recently inflammation, have been pointed out as the leading causes of brain aging. Thereby, the consumption or administration of antioxidant and anti-inflammatory molecules, such as polyphenols, is a beneficial strategy recommended for preventing brain aging and several brain age-related diseases. METHODS AND RESULTS: Several studies suggest that long term consumption of dietary polyphenols offers protection against development of neurodegenerative diseases. These beneficial effects are in part due to their antioxidant and anti-inflammatory properties, together with their positive role in the modulation of processes involved in the physiopathology of several neurodegenerative diseases (e.g., epigenetic factors, amyloid deposition, cholinesterase inhibition, autophagy, and neurotrophic factors, among others). Altogether, these molecules open the door to the research of new neuroprotective strategies. This review summarizes the latest discoveries in how polyphenols can exert positive effects on brain health in aging, emphasizing those effects on the diseases that most commonly affect the brain during aging: Parkinson's Disease (PD), Alzheimer's disease (AD), dementia and depression. Moreover, within are addressed the epigenetic effects of polyphenols as possible mediators in their positive effects on brain health, and the future challenges of research in this topic Conclusion: In brief, this review presents a report of state-of the art knowledge regarding the positive influences of polyphenols on the most common brain age-related diseases as well as in healthy brain aging.

Chronic α-Tocopherol Increases Central Monoamines Synthesis and Improves Cognitive and Motor Abilities in Old Rats.

Limiting enzymes in the synthesis of brain monoamines seems to be susceptible to oxidative damage, one of the most important factors in aging. It has been suggested that the use of anti-oxidants can reduce the rate of free radical production related with aging and the associated damage. Therefore, this study aims to analyze the effects of the chronic treatments with the anti-oxidant α-tocopherol (vitamin E) on central monoamines (high-performance liquid chromatography [HPLC] analysis) mediating cognitive functions, as well as on the evaluation of memory and motor abilities in old rats measured by radial maze, Barnes maze, novel object recognition test, and rotarod test. Results show that α-tocopherol significantly increased in a dose- and/or time-dependent manner the synthesis rate and the levels of monoaminergic neurotransmitters (serotonin, dopamine, and noradrenaline) in the hippocampus and striatum, brain regions involved in memory processing and motor coordination. These positive neurochemical effects, largely due to an increased activity of the limiting enzymes in monoamines synthesis, tryptophan hydroxylase and tyrosine hydroxylase, were accompanied by an improvement in cognitive and motor abilities in old rats. Altogether these findings suggest that α-tocopherol exhibits neuroprotective actions in old rats; thus, diets with α-tocopherol might represent a promising strategy to mitigate or delay the cognitive and motor decline associate with aging and related-diseases.

Caloric restriction, resveratrol and melatonin: Role of SIRT1 and implications for aging and related-diseases.

Aging is an inevitable and multifactorial biological process. Free radicals have been implicated in aging processes; it is hypothesized that they cause cumulative oxidative damage to crucial macromolecules and are responsible for failure of multiple physiological mechanisms. However, recent investigations have also suggested that free radicals can act as modulators of several signaling pathways such as those related to sirtuins. Caloric restriction is a non-genetic manipulation that extends lifespan of several species and improves healthspan; the belief that many of these benefits are due to the induction of sirtuins has led to the search for sirtuin activators, especially sirtuin 1, the most studied. Resveratrol, a polyphenol found in red grapes, was first known for its antioxidant and antifungal properties, and subsequently has been reported several biological effects, including the activation of sirtuins. Endogenously-produced melatonin, a powerful free radical scavenger, declines with age and its loss contributes to degenerative conditions of aging. Recently, it was reported that melatonin also activates sirtuins, in addition to other functions, such as regulator of circadian rhythms or anti-inflammatory properties. The fact that melatonin and resveratrol are present in various foods, exhibiting possible synergistic effects, suggests the use of dietary ingredients to promote health and longevity.

Role of ferrocyanides in the prebiotic synthesis of α-amino acids.

We investigated the synthesis of α-amino acids under possible prebiotic terrestrial conditions in the presence of dissolved iron (II) in a simulated prebiotic ocean. An aerosol-liquid cycle with a prebiotic atmosphere is shown to produce amino acids via Strecker synthesis with relatively high yields. However, in the presence of iron, the HCN was captured in the form of a ferrocyanide, partially inhibiting the formation of amino acids. We showed how HCN captured as Prussian Blue (or another complex compound) may, in turn, have served as the HCN source when exposed to UV radiation, allowing for the sustained production of amino acids in conjunction with the production of oxyhydroxides that precipitate as by-products. We conclude that ferrocyanides and related compounds may have played a significant role as intermediate products in the prebiotic formation of amino acids and oxyhydroxides, such as those that are found in iron-containing soils and that the aerosol cycle of the primitive ocean may have enhanced the yield of the amino acid production.

Cognitive improvement by acute growth hormone is mediated by NMDA and AMPA receptors and MEK pathway.

It has been reported that Growth hormone (GH) has an immediate effect enhancing excitatory postsynaptic potentials mediated by AMPA and NMDA receptors in hippocampal area CA1. As GH plays a role in adult memory processing, this work aims to study the acute effects of GH on working memory tasks in rodents and the possible involvement of NMDA and AMPA receptors and also the MEK/ERK signalling pathway. To evaluate memory processes, two different tests were used, the spatial working memory 8-arm radial maze, and the novel object recognition as a form of non-spatial working memory test. Acute GH treatment (1mg/kg i.p., 1h) improved spatial learning in the radial maze respect to the control group either in young rats (reduction of 46% in the performance trial time and 61% in the number of errors), old rats (reduction of 38% in trial time and 48% in the number of errors), and adult mice (reduction of 32% in the performance time and 34% in the number of errors). GH treatment also increased the time spent exploring the novel object respect to the familiar object compared to the control group in young rats (from 63% to 79%), old rats (from 53% to 70%), and adult mice (from 61 to 68%). The improving effects of GH on working memory tests were blocked by the NMDA antagonist MK801 dizocilpine (0.025 mg/kg i.p.) injected 10 min before the administration of GH, in both young and old rats. In addition, the AMPA antagonist DNQX (1mg/kg i.p.) injected 10 min before the administration of GH to young rats, blocked the positive effect of GH. Moreover, in mice, the MEK inhibitor SL 327 (20mg/kg i.p.) injected 30 min before the administration of GH, blocked the positive effect of GH on radial maze and the novel object recognition. In conclusion, GH improved working memory processes through both glutamatergic receptors NMDA and AMPA and it required the activation of extracellular MEK/ERK signalling pathway. These effects could be related to the enhancement of excitatory synaptic transmission in the hippocampus reported by GH.

Asymmetric sleep in apneic human patients.

Unilateral sleep in marine mammals has been considered to be a defense against airway obstruction, as a sentinel for pod maintenance, and as a thermoregulatory mechanism. Birds also show asymmetric sleep, probably to avoid predation. The variable function of asymmetric sleep suggests a general capability for independence between brain hemispheres. Patients with obstructive sleep apnea share similar problems with diving mammals, but their eventual sleep asymmetry has received little attention. The present report shows that human sleep apnea patients also present temporary interhemispheric variations in dominance during sleep, with significant differences when comparing periods of open and closed airways. The magnitude of squared coherence, an index of interhemispheric EEG interdependence in phase and amplitude, rises in the delta EEG range during apneic episodes, while the phase lag index, a measure of linear and nonlinear interhemispheric phase synchrony, drops to zero. The L index, which measures generalized nonlinear EEG interhemispheric synchronization, increases during apneic events. Thus, the three indexes show significant and congruent changes in interhemispheric symmetry depending on the state of the airways. In conclusion, when confronted with a respiratory challenge, sleeping humans undergo small, but significant, breathing-related oscillations in interhemispheric dominance, similar to those observed in marine mammals. The evidence points to a relationship between cetacean unihemispheric sleep and their respiratory challenges.

Simple Organics and Biomonomers Identified in HCN Polymers: An Overview.

Hydrogen cyanide (HCN) is a ubiquitous molecule in the Universe. It is a compound that is easily produced in significant yields in prebiotic simulation experiments using a reducing atmosphere. HCN can spontaneously polymerise under a wide set of experimental conditions. It has even been proposed that HCN polymers could be present in objects such as asteroids, moons, planets and, in particular, comets. Moreover, it has been suggested that these polymers could play an important role in the origin of life. In this review, the simple organics and biomonomers that have been detected in HCN polymers, the analytical techniques and procedures that have been used to detect and characterise these molecules and an exhaustive classification of the experimental/environmental conditions that favour the formation of HCN polymers are summarised. Nucleobases, amino acids, carboxylic acids, cofactor derivatives and other compounds have been identified in HCN polymers. The great molecular diversity found in HCN polymers encourages their placement at the central core of a plausible protobiological system.

New insights into the characterization of 'insoluble black HCN polymers'.

The data presented here provide a novel contribution to the understanding of the structural features of HCN polymers and could be useful in further development of models for prebiotic chemistry. The interpretation of spectroscopic and analytical data, along with previous results reported by other authors, allowed us to propose a mechanism for the aqueous polymerization of HCN from its primary and simplest isolated oligomer, the diaminomaleonitrile (DAMN) tetramer. We suggest that 'insoluble black HCN polymers' are formed by an unsaturated complex matrix, which retains a significant amount of H(2) O and important bioorganic compounds or their precursors. This polymeric matrix can be formed by various motifs of imidazoles and cyclic amides, among others. The robust formation of HCN polymers assayed under several conditions seems to explain the plausible ubiquity of these complex substances in space.

Asymmetric sleep in rats.

Five Wistar rats were surgically implanted with cortical and parietal electrodes for conventional polysomnography to test for sleep-related EEG asymmetries during 48 hours of continuous recording. When the animals were grouped not according to right-left dominance (which would represent a population bias) but instead according to preferred vs non-preferred hemisphere, significant light/dark circadian changes in side dominance were found in delta power during NREM; in theta and beta power during REM; and in alpha 1, alpha 2, and theta power during wakefulness. The changes have been interpreted as a response to temporal variations in the capability to respond to environmental challenges.

Effects induced by cannabinoids on monoaminergic systems in the brain and their implications for psychiatric disorders.

The endocannabinoid system and CB(1) receptors participate in the control of emotional behavior and mood through a functional coupling with the classic monoaminergic systems. In general, the acute stimulation of CB(1) receptors increases the activity (spontaneous firing rate) of noradrenergic (NE), serotonergic (5-HT) and dopaminergic (DA) neurons as well as the synthesis and/or release of the corresponding neurotransmitter in specific brain regions. Notably, the antagonist/inverse agonist rimonabant (SR141617A) can decrease the basal activity of NE and 5-HT neurons, suggesting a tonic/constitutive regulation of these neuronal systems by endocannabinoids acting at CB(1) receptors. Monoaminergic systems are modulated via CB(1) receptors by direct or indirect effects depending on the localization of this inhibitory receptor, which can be present on monoaminergic neurons themselves and/or inhibitory (GABAergic) and/or excitatory (glutamatergic) regulatory neurons. The repeated stimulation of CB(1) receptors is not associated with the induction of tolerance (receptor desensitization) on the activity of NE, 5-HT and DA neurons, in contrast to chronic agonist effects on neurotransmitter synthesis and/or release in some brain regions. CB(1) receptor desensitization may alter the direct and/or indirect effects of cannabinoid drugs modulating the functionality of monoaminergic systems. The sustained activation of monoaminergic neurons by cannabinoid drugs can also be related to changes in the function of presynaptic inhibitory α(2)-adrenoceptors or 5-HT(1A) receptors (autoreceptors and heteroreceptors), whose sensitivity is downregulated or upregulated upon chronic CB(1) agonist exposure. The functional interactions between endocannabinoids and monoaminergic systems in the brain indicate a potential role for CB(1) receptor signaling in the neurobiology of various psychiatric disorders, including major depression and schizophrenia as the major syndromes.

Prebiotic synthesis of protobiopolymers under alkaline ocean conditions.

Clasically, prebiotic chemistry has focused on the production and identification of simple organic molecules, many of them forming part of "intractable polymers" named tholins. In a previous work, we demonstrated that in experiments using an external energy source and inorganic carbon the aqueous aerosols improved the formation of hydrophilic tholins. Herein, we elucidate the role of pH (from 4 to 12) in prebiotic experiments using saline aqueous aerosols, spark discharges and an atmosphere containing CH(4). At all values of pH, the saline aqueous aerosols increased the production of a significant variety of carboxylic acids that could have been present in a primitive Krebs cycle. Moreover, the study for the first time of hydrophilic tholins by 2-D electrophoresis revealed that these are formed by a set of unexpected heavy polymeric species. The initial alkaline conditions significantly increased both the apparent molecular weight of polymeric species up to 80 kDa and their diversity. We propose the term of protobiopolymers to denote those polymeric species fractionated by 2-D electrophoresis since these are formed by biomolecules present in living systems and show diversity in length as well as in functional groups. Thus, aerosols formed in simulated alkaline ocean conditions could provide an optimal medium for the formation of the primeval materials that could be precursors to the emergence of life.

Control y vigilancia en fronteras. Papel de sanidad exterior durante las fases de contención de la pandemia (H1N1) 2009 / Health control at international borders. The role of foreign health during the containment phases of the Pandemic (H1N1) 2009

Los controles sanitarios en fronteras, establecidos con el objeti-vo de retrasar la entrada del virus pandémico en España, constituyen una de las actividades propias de las fases de contención de la enfer-medad. Su puesta en práctica como estrategia de salud pública en respuesta a epidemias es responsabilidad de la Dirección General de Salud Pública y Sanidad Exterior del Ministerio de Sanidad y Políti-ca Social, a través de la Subdirección General de Sanidad Exterior, y para ello se requiere una actuación coordinada con otros organismos implicados. Este trabajo tiene como finalidad describir las actuaciones reali-zadas en los aeropuertos internacionales durante dichas fases, así como evaluar su efectividad en la consecución del objetivo para el que fueron diseñadas. En este sentido, se establece una hipótesis que trata de explicar cómo las medidas adoptadas por Sanidad Exterior y la colaboración con los Servicios de Vigilancia Epidemiológica de las Comunidades Autónomas podrían haber contribuido a retrasar la propagación del virus en nuestro país. Se destaca la necesidad de consolidar los sistemas de vigilancia en fronteras potenciando dicha colaboración, así como la importan-cia de diseñar una estrategia clara de comunicación a la población en estos escenarios, que debe acompañar a la implementación de las demás medidas para evitar situaciones de incertidumbre(AU)

As a public health strategy in responding to epidemics, sanitary checks at borders to delay the entry of the pandemic virus into Spain are part of the containment phases activities. Their implementation is the responsibility of the Foreign Health Department and requires a coordinated action with other agencies involved in the response. This paper describes the actions undertaken at international air-ports during these phases and evaluates its efficacy in the execution of their objective. We establish a hypothesis to explain how the mea-sures undertaken by Foreign Health and the collaboration with the National Surveillance System may have contributed to delay the spread of the virus into our country. We want to emphasize the need for consolidating the border con-trol surveillance system and improving collaboration, as well as the importance of designing a clear communication strategy for the population in these settings. Together these measures, along with others, will prevent situations of uncertainty(AU)