ginsenoside rg3 Another important aspect to be considered in

Another important aspect to be considered in the context of our findings is the milieu of Atahualpa residents, since light and noise pollution is virtually nonexistent during sleep hours. These factors, which are known to negatively influence sleep quality [22], might enhance potential detrimental effects of caffeine intake in some individuals. The absence of light and noise pollution is common to most rural villages of developing countries and is a different scenario to that seen in most of the developed world. Such differences must be taken into account when analyzing the results of the present study, which might not represent the reality of urban centers. We did not investigated genetic variations in the Adenosine A2a receptor gene or other candidates genes that may explain the “resistance” of caffeine intake [9,10]. This is a limitation of the present study, particularly in view of the ethnic homogeneity of our participants. It is also possible that relatively small amounts of caffeine intake by some Atahualpa residents accounted for the lack of effect in sleep quality in the entire cohort. On the contrary, the population-based design with unbiased selection of participants and the field instruments used for obtaining information about total amount of caffeine intake and sleep quality, argue for the strengths of our findings. Further support for the validity of our results are the associations observed in the separate exposure and effect models. Caffeine intake was inversely associated with symptoms of depression and directly with total cholesterol blood levels, as reported by other investigators [23,24], and poor sleep quality was directly associated with age, symptoms of depression and poor physical activity, as previously described [25,26].
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Introduction Since Metalnikov and Chorine [1], pioneers who described the relationship between the ginsenoside rg3 and the immune processes in the 1920\'s, neuroimmunomodulation has been extensively explored by different research groups aiming to unveil how the immune system interacts with the CNS, from cellular [2] to behavioral [3] levels. Particularly, It has been found that cellular and humoral immunity may be influenced by Pavlovian conditioning. Pairing a novel drinking solution (conditioned stimulus-CS) with an immunomodulatory drug (unconditioned stimulus-US) results in a modulation of the immune function. Findings in conditioned immunosuppression [4] raised the question of whether the development of an immune disorder could be delayed by the classical conditioning paradigm. To answer this question, Ader and Cohen [5] investigated the progression of proteinuria and the lifespan of spontaneous lupus prone mice under a classical conditioning paradigm in which a saccharin-flavored drink is paired with the injection of an effective immune-suppressing drug cyclophosphamide. The results were consistent with their hypothesis, confirming the biological impact of conditioned immunomodulation revealed by the modulation of the lifespan. Although immune system conditioning has been extensively studied, the temporal aspect of this form of associative learning has been widely overlooked. A growing body of evidence indicates daily modulation in learning and states that both morphological and physiological integrity of circadian timekeeping system are critical for learning and memory processes [6–9]. Davies et al. [10] demonstrated a 24-h rhythm in passive avoidance behavior. Rats trained and tested with a 4-h interval throughout a 24-h cycle exhibited more pronounced memory retention during the light phase of the LD cycle than during the dark phase. Moreover, the “time-stamp” phenomenon, which comprises the strong relationship between the performance in a learning task and the circadian phase of prior training, has been reported both for reward-conditioned place preference and for avoidance-based place leaning in hamsters [11,12] even for animals carrying the Tau mutation and displaying a short 20h-period of rest-activity rhythm [13].