Neuroepigenetics and Alzheimer's Disease: An Update

Epigenetics is the study of changes in gene expression which may be triggered by both genetic and environmental factors, and independent from changes to the underlying DNA sequence-a change in phenotype without a change in genotype-which in turn affects how cells read genes. Epigenetic changes represent a regular and natural occurrence but can be influenced also by factors such as age, environment, and disease state. Epigenetic modifications can manifest themselves not only as the manner in which cells terminally differentiate, but can have also deleterious effects, resulting in diseases such as cancer. At least three systems including DNA methylation, histone modification, and non-coding RNA (ncRNA)-associated gene silencing are thought to initiate and sustain epigenetic change. For example, in Alzheimer's disease (AD), both genetic and non-genetic factors contribute to disease etiopathology. While over 250 gene mutations have been related to familial AD, less than 5% of AD cases are explained by known disease genes. More than likely, non-genetic factors, probably triggered by environmental factors, are causative factors of late-onset AD. AD is associated with dysregulation of DNA methylation, histone modifications, and ncRNAs. Among the classes of ncRNA, microRNAs (miRNAs) have a well-established regulatory relevance. MicroRNAs are highly expressed in CNS neurons, where they play a major role in neuron differentiation, synaptogenesis, and plasticity. MicroRNAs impact higher cognitive functions, as their functional impairment is involved in the etiology of neurological diseases, including AD. Alterations in the miRNA network contribute to AD disease processes, e.g., in the regulation of amyloid peptides, tau, lipid metabolism, and neuroinflammation. MicroRNAs, both as biomarkers for AD and therapeutic targets, are in the early stages of exploration. In addition, emerging data suggest that altered transcription of long ncRNAs, endogenous, ncRNAs longer than 200 nucleotides, may be involved in an elevated risk for AD

Cross-cultural differences in delayed discounting rates of monetary rewards

Przeprowadzone w pracy badanie testuje hipotezę dotyczącą istnienia różnic w tempie dyskontowania odroczonych nagród pieniężnych między kulturami indywidualizmu i kolektywizmu. Dotychczasowe wyniki badań w tym zakresie wskazują, że proces dyskontowania odroczonych nagród może stanowić jeden z czynników wyjasniającymch sposób dokonywania wyborów w kulturach indywidualizmu i kolektywizmu. Niemniej w literaturze przedmiotu nie wszystkie badania wydają się potwierdzać istnienie związku pomiędzy procesem dyskontowania odroczonych nagród z różnicami w sposobie dokonywania wyborów. Celem badania było zweryfikowanie niespójnych doniesień dotyczących występowania różnic w tempie dyskontowania odroczonych nagród pieniężnych w kulturach indywidualizmu i kolektywizmu oraz próba określenia związku tempa dyskontowania odroczonych nagród z krajami zamieszkania osób badanych, w których nie prowadzono dotychczas badań międzykulturowych nad dyskontowaniem. Przebadano 50 osób z każdego z następujących krajów: Chiny, Mauritius, Polska, Republika Południowej Afryki i Stany Zjednoczone Ameryki. Dokonano pomiaru tempa dyskontowania odroczonych nagród pieniężnych przy pomocy zmodyfikowanego kwestionariusza autorstwa Ostaszewskiego (1997). Wskaźnikiem tempa dyskontowania odroczonych nagród pieniężnych była wielkość obszaru pod krzywą dyskontową (AUC). Przeprowadzona analiza wykazała, iż kultury indywidualizmu (Mauritius, Polska, RPA i USA) szybciej dyskontują odroczone nagródy w porównaniu z kulturą kolektywizmu (Chiny). Porównując poszczególne kraje okazuje się, iż występuje różnica w tempie dyskontowania w obrębie kultur indywidualizmu, wyrażająca się w szybszym tempie dyskontowania Amerykanów od Maurytyjczyków, Polaków i obywateli Republiki Południowej Afryki. Ponadto wskazano na zależność pomiędzy tempem dyskontowania a wielkością nagrody.The aim of the study was to assess differences in the discounting rate of delayed monetary rewards among individualistic and collectivistic cultures. Known studies in this field indicate that the process of discounting delayed monetary rewards may be one of the factors describing choice patterns in individualistic and collectivistic cultures. So far, results from known studies prove to be inconsistent. The main aim of the study was to verify these inconsistent results testing the same countries that have already be the subject of previous studies and also to determine the relationship among the rate of discounting and culture in countries not yet tested. 50 test subjects were selected from five countries: China, Mauritius, Poland, Republic of South Africa and United States of America. The rate of discounting index was the area under the discounting curve (AUC). The results of the study showed that the rate of discounting delayed monetary rewards is steeper in individualistic than in collectivistic cultures

Exploring the salience of religious identity on the mental health of the Mauritian adult

Abstract Religion is undeniably one of the core components of the Mauritian identity, with religious values and principles woven into the Mauritian fabric. Due to the existing gaps in the research of religion and mental health in the Mauritian community, this study sought to examine the impact of religious identity on the psychological well-being of the typical Mauritian. 276 quantitative responses were retrieved, and 12 participants from the 3 main religious groups in the country were interviewed for an in-depth analysis of their religious identities. Results strongly demonstrated positive links between the 3 dimensions of religious identity and total well-being; religious identity achievement [χ2 (1680) = 2228 p < 0.05, Cramer’s V = 0.537]; religious affirmation and belongingness [χ2 (1620) = 2041, p < 0.05, Cramer’s V = 0.523], and religious faith and practices [χ2 (1620) = 1757, p < 0.05, Cramer’s V = 0.487]. Religious practice strongly associated with emotional stability [χ2 (246) = 296.15, p < 0.05, Cramer’s V = 0.432] and happiness [χ2 (48) = 73.86, p < 0.05, Cramer’s V = 0.211]. Demographically, educational attainment did not affect religious identification in the Mauritian community. The findings clearly demonstrate the need for an integrative system with ingroup beliefs and traditions embedded into models of recovery for psychological disorders. Mental health professionals should consider alternative approaches, reeling in religion and spiritual dimensions of healing into conventional therapies. The role of religious settings in improving psychological treatment adherence and fostering mental well-being should not be downplayed

A "timed" kiss is essential for reproduction:Lessons from mammalian studies

Reproduction is associated with the circadian system, primarily as a result of the connectivity between the biological clock in the suprachiasmatic nucleus (SCN) and reproduction-regulating brain regions, such as preoptic area (POA), anteroventral periventricular nucleus (AVPV) and arcuate nucleus (ARC). Networking of the central pacemaker to these hypothalamic brain regions is partly represented by close fiber appositions to specialised neurons, such as kisspeptin and gonadotropin-releasing hormone (GnRH) neurons; accounting for rhythmic release of gonadotropins and sex steroids. Numerous studies have attempted to dissect the neurochemical properties of GnRH neurons, which possess intrinsic oscillatory features through the presence of clock genes to regulate the pulsatile and circadian secretion. However, less attention has been given to kisspeptin, the upstream regulator of GnRH and a potent mediator of reproductive functions including puberty. Kisspeptin exerts its stimulatory effects on GnRH secretion via its cognate Kiss-1R receptor that is co-expressed on GnRH neurons. Emerging studies have found that kisspeptin neurons oscillate on a circadian basis and that these neurons also express clock genes that are thought to regulate its rhythmic activities. Based on the fiber networks between the SCN and reproductive nuclei such as the POA, AVPV, ARC, it is suggested that interactions among the central biological clock and reproductive neurons ensure optimal reproductive functionality. Within this neuronal circuitry, kisspeptin neuronal system is likely to ‘time’ reproduction in a long term during development and ageing, in a medium term to regulate circadian or estrus cycle, and in a short term to regulate pulsatile GnRH secretion

Discovering the Health Promoting Potential of Fermented Papaya Preparation—Its Future Perspectives for the Dietary Management of Oxidative Stress During Diabetes

The simplistic morphological characteristics of Carica papaya fruit or &ldquo;pawpaw&rdquo; should not be the cause for underestimating its potential as a nutraceutical. The market for papaya has been expanding at a staggering rate, partly due to its applicability as a biofortified product, but also due to its phytochemical properties and traditional health benefits. Papaya or formulations of fermented papaya promotion (FPP) display effective free radical scavenging abilities thought to be influenced by its phenolic, carotenoid, flavonoid, or amino acid profile. The antioxidant properties of FPP have been extensively reported in literature to potently target a broad spectrum of free radical-induced diseases ranging from neurological impairments, such as senile dementia, to systemic diseases, to its interference at the cellular level and the support of normal biological ageing processes. FPP has thus been extensively investigated for its ability to exert cellular protective effects and reduce oxidative stress via the mitigation of genetic damage, reduction of lipid peroxidation, and enzymatic inactivation in specific diseases. The focus of this review is to appraise the potential of oxidative stress reduction strategies of FPP and discuss its holistic approach in disease prevention and management, with a particular focus on diabetes and cancer. However, with the current lack of information surrounding its mechanism of action, this review wishes to set the stage and aspire researchers to more profoundly investigate molecular pathways related to how FPP can unequivocally contribute to wellness in an aging population

Current and emerging avenues for Alzheimer's disease drug targets

Alzheimer's disease (AD), the most frequent cause of dementia, is escalating as a global epidemic and so far, there is no cure nor treatment to alter its progression. The most important feature of the disease is neuronal death and loss of cognitive functions, caused probably from several pathological processes in the brain. The main neuropathological features of AD are widely described: amyloid beta (Aβ) plaques and neurofibrillary tangles of the aggregated protein tau, which contribute to the disease. Nevertheless, AD brains suffer from a variety of alterations in function, such as energy metabolism, inflammation, and synaptic activity. The latest decades have seen an explosion of genes and molecules that can be employed as targets aiming to improve brain physiology, which can result in preventive strategies for AD. Moreover, therapeutics using these targets can help AD brains to sustain function during the development of AD pathology. Here, we review broadly recent information for potential targets that can modify AD through diverse pharmacological and non‐pharmacological approaches including gene therapy. We propose that AD could be tackled using combination therapies including Aβ and tau, but also considering insulin and cholesterol metabolism, vascular function, synaptic plasticity, epigenetics, neurovascular junction and blood‐brain barrier targets that have been studied recently. We also make a case for the role of gut microbiota in AD. Our hope is to promote the continuing research of diverse targets affecting AD and promote diverse targeting as a near‐future strategy

Kisspeptin modulates sexual and emotional brain processing in humans

BACKGROUND. Sex, emotion, and reproduction are fundamental and tightly entwined aspects of human behavior. At a population level in humans, both the desire for sexual stimulation and the desire to bond with a partner are important precursors to reproduction. However, the relationships between these processes are incompletely understood. The limbic brain system has key roles in sexual and emotional behaviors, and is a likely candidate system for the integration of behavior with the hormonal reproductive axis. We investigated the effects of kisspeptin, a recently identified key reproductive hormone, on limbic brain activity and behavior. METHODS. Using a combination of functional neuroimaging and hormonal and psychometric analyses, we compared the effects of kisspeptin versus vehicle administration in 29 healthy heterosexual young men. RESULTS. We demonstrated that kisspeptin administration enhanced limbic brain activity specifically in response to sexual and couple-bonding stimuli. Furthermore, kisspeptin’s enhancement of limbic brain structures correlated with psychometric measures of reward, drive, mood, and sexual aversion, providing functional significance. In addition, kisspeptin administration attenuated negative mood. CONCLUSIONS. Collectively, our data provide evidence of an undescribed role for kisspeptin in integrating sexual and emotional brain processing with reproduction in humans. These results have important implications for our understanding of reproductive biology and are highly relevant to the current pharmacological development of kisspeptin as a potential therapeutic agent for patients with common disorders of reproductive function. FUNDING. National Institute for Health Research (NIHR), Wellcome Trust (Ref 080268), and the Medical Research Council (MRC)