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In neurons, the convergence of multiple intracellular signaling cascades leading to cAMP-responsive element-binding protein (CREB) activation suggests that this transcription factor plays a critical role in integrating different inputs and mediating appropriate neuronal responses. The nature of this transcriptional response depends on both the type and strength of the stimulus and the cellular context. CREB-dependent gene expression has been involved in many different aspects of nervous system function, from embryonic development to neuronal survival, and synaptic, structural, and intrinsic plasticity. Here, we first review the different methodological approaches used to genetically manipulate CREB activity and levels in neurons in vivo in the adult brain, including recombinant viral vectors, mouse transgenesis, and gene-targeting techniques. We then discuss the impact of these approaches on our understanding of CREB’s roles in neuronal plasticity and memory in rodents. Studies combining these genetic approaches with electrophysiology and behavior provide strong evidence that CREB is critically involved in the regulation of synaptic plasticity, intrinsic excitability, and long-term memory formation. These findings pave the way for the development of novel therapeutic strategies to treat memory disorders.

Health awareness initiatives are frequent but their efficacy is a matter of controversy. We have investigated the effect of the Eating Disorder Awareness Week and Wake Up Weight Watchers campaigns on Twitter. We aimed to examine whether the Eating Disorder Awareness Week and Wake Up Weight Watchers initiatives increased the volume and dissemination of Twitter conversations related to eating disorders and investigate what content generates the most interest on Twitter. Over a period of 12 consecutive days in 2018, we collected tweets containing the hashtag #wakeupweightwatchers and hashtags related to Eating Disorder Awareness Week (#eatingdisorderawarenessweek, #eatingdisorderawareness, or #EDAW), with the hashtag #eatingdisorder as a control. The content of each tweet was rated as medical, testimony, help offer, awareness, pro-ana, or anti-ana. We analyzed the number of retweets and favorites generated, as well as the potential reach and impact of the hashtags and the characteristics of contributors. The number of #wakeupweightwatchers tweets was higher than that of Eating Disorder Awareness Week and #eatingdisorder tweets (3900, 2056, and 1057, respectively). The content of tweets was significantly different between the hashtags analyzed (P<.001). Medical content was lower in the awareness campaigns. Awareness and help offer content were lower in #wakeupweightwatchers tweets. Retweet and favorite ratios were highest in #wakeupweightwatchers tweets. Eating Disorder Awareness Week achieved the highest impact, and very influential contributors participated. Both awareness campaigns effectively promoted tweeting about eating disorders. The majority of tweets did not promote any specific preventive or help-seeking behaviors.

The lysine acetyltransferases type 3 (KAT3) family members CBP and p300 are important transcriptional co-activators, but their specific functions in adult post-mitotic neurons remain unclear. Here, we show that the combined elimination of both proteins in forebrain excitatory neurons of adult mice resulted in a rapidly progressing neurological phenotype associated with severe ataxia, dendritic retraction and reduced electrical activity. At the molecular level, we observed the downregulation of neuronal genes, as well as decreased H3K27 acetylation and pro-neural transcription factor binding at the promoters and enhancers of canonical neuronal genes. The combined deletion of CBP and p300 in hippocampal neurons resulted in the rapid loss of neuronal molecular identity without de- or transdifferentiation. Restoring CBP expression or lysine acetylation rescued neuronal-specific transcription in cultured neurons. Together, these experiments show that KAT3 proteins maintain the excitatory neuron identity through the regulation of histone acetylation at cell type-specific promoter and enhancer regions. Neuronal identity maintenance is highly regulated. Here, the authors showed that CBP and p300 safeguard neuronal identity through histone acetylation at promoters and enhancers of neuronal specific genes. The loss of both CBP and p300 impairs gene expression, circuit activity, and behavior in mice.

Background: Antiobesity drugs are prescribed for the treatment of obesity in conjunction with healthy eating, physical activity, and behavior modification. However, poor adherence rates have been reported. Attitudes or beliefs toward medications are important to ascertain because they may be associated with patient behavior. The analysis of tweets has become a tool for health research. Objective: The aim of this study is to investigate the content and key metrics of tweets referring to antiobesity drugs. Methods: In this observational quantitative and qualitative study, we focused on tweets containing hashtags related to antiobesity drugs between September 20, 2019, and October 31, 2019. Tweets were first classified according to whether they described medical issues or not. Tweets with medical content were classified according to the topic they referred to: side effects, efficacy, or adherence. We additionally rated it as positive or negative. Furthermore, we classified any links included within a tweet as either scientific or nonscientific. Finally, the number of retweets generated as well as the dissemination and sentiment score obtained by the antiobesity drugs analyzed were also measured. Results: We analyzed a total of 2045 tweets, 945 of which were excluded according to the criteria of the study. Finally, 320 out of the 1,100 remaining tweets were also excluded because their content, although related to drugs for obesity treatment, did not address the efficacy, side effects, or adherence to medication. Liraglutide and semaglutide accumulated the majority of tweets (682/780, 87.4%). Notably, the content that generated the highest frequency of tweets was related to treatment efficacy, with liraglutide-, semaglutide-, and lorcaserin-related tweets accumulating the highest proportion of positive consideration. We found the highest percentages of tweets with scientific links in those posts related to liraglutide and semaglutide. Semaglutide-related tweets obtained the highest probability of likes and were the most disseminated within the Twitter community. Conclusions: This analysis of posted tweets related to antiobesity drugs shows that the interest, beliefs, and experiences regarding these pharmacological treatments are heterogeneous. The efficacy of the treatment accounts for the majority of interest among Twitter users.

Hikikomori is a severe form of social withdrawal, originally described in Japan but recently reported in other countries. Debate exists as to what extent hikikomori is viewed as a problem outside of the Japanese context. We aimed to explore perceptions about hikikomori outside Japan by analyzing Western language content from the popular social media platform, Twitter. We conducted a mixed methods analysis of all publicly available tweets using the hashtag #hikikomori between February 1 and August 16, 2018, in 5 Western languages (Catalan, English, French, Italian, and Spanish). Tweets were first classified as to whether they described hikikomori as a problem or a nonproblematic phenomenon. Tweets regarding hikikomori as a problem were then subclassified in terms of the type of problem (medical, social, or anecdotal) they referred to, and we marked if they referenced scientific publications or the presence of hikikomori in countries other than Japan. We also examined measures of interest in content related to hikikomori, including retweets, likes, and associated hashtags. A total of 1042 tweets used #hikikomori, and 656 (62.3%) were included in the content analysis. Most of the included tweets were written in English (44.20%) and Italian (34.16%), and a majority (56.70%) discussed hikikomori as a problem. Tweets referencing scientific publications (3.96%) and hikikomori as present in countries other than Japan (13.57%) were less common. Tweets mentioning hikikomori outside Japan were statistically more likely to be retweeted (P=.01) and liked (P=.01) than those not mentioning it, whereas tweets with explicit scientific references were statistically more retweeted (P=.01) but not liked (P=.10) than those without that reference. Retweet and like figures were not statistically significantly different among other categories and subcategories. The most associated hashtags included references to Japan, mental health, and the youth. Hikikomori is a repeated word in non-Japanese Western languages on Twitter, suggesting the presence of hikikomori in countries outside Japan. Most tweets treat hikikomori as a problem, but the ways they post about it are highly heterogeneous.

There is still much controversy regarding the epidemiology of endometriosis. The objective of this work is to conduct a systematic review, and if possible, proceed with a meta-analysis of studies that have analyzed the incidence and prevalence of this condition among women in the general population. The inclusion criteria were papers published after 1997 that had reported data of the incidence or prevalence of endometriosis. The PubMed search engine was used to identify papers meeting the inclusion criteria from 1997 to 2019, with an additional manual search for the identification of potentially eligible studies. The search was limited to papers published in English. The risk of bias was assessed according to the Joanna Briggs Institute Critical Appraisal Checklist. As a result, 27 papers, which included a total of 28,660,652 women, were classified according to the type of design and sources of information in five subgroups. Pooled estimates of prevalence for studies with self-reported data were 0.05 (95% CI: 0.03; 0.06), 0.01 for population-based integrated information systems (95% CI: 0.01; 0.02), and 0.04 (95% CI 0.04; 0.05) in studies using other designs. The pooled incidence rate of endometriosis was: 1.36 per 1000 person-years (PY) (95% CI: 1.09; 1.63) for studies based on hospital discharges, 3.53 per 1000 PY (95% CI: 2.06; 4.99) for cohort studies, and 1.89 per 1000 PY (95% CI: 1.42; 2.37) for population-based integrated information systems. Meta-analysis indicated high heterogeneity based on I-squared statistics. This significant variability may not only be due to methodological issues and the specific limitations of the different designs and data analyzed, including case definitions and subject selection strategies, but also to the inherent heterogeneity of endometriosis. Epidemiological studies with appropriate study designs remain necessary to provide a valid estimation of the population burden of endometriosis.

Twitter is an indicator of real-world performance, thus, is an appropriate arena to assess the social consideration and attitudes toward psychosis. The aim of this study was to perform a mixed-methods study of the content and key metrics of tweets referring to psychosis in comparison with tweets referring to control diseases (breast cancer, diabetes, Alzheimer, and human immunodeficiency virus). Each tweet's content was rated as nonmedical (NM: testimonies, health care products, solidarity or awareness and misuse) or medical (M: included a reference to the illness's diagnosis, treatment, prognosis, or prevention). NM tweets were classified as positive or pejorative. We assessed the appropriateness of the medical content. The number of retweets generated and the potential reach and impact of the hashtags analyzed was also investigated. We analyzed a total of 15,443 tweets: 8055 classified as NM and 7287 as M. Psychosis-related tweets (PRT) had a significantly higher frequency of misuse 33.3% (212/636) vs 1.15% (853/7419; P<.001) and pejorative content 36.2% (231/636) vs 11.33% (840/7419; P<.001). The medical content of the PRT showed the highest scientific appropriateness 100% (391/391) vs 93.66% (6030/6439; P<.001) and had a higher frequency of content about disease prevention. The potential reach and impact of the tweets related to psychosis were low, but they had a high retweet-to-tweet ratio. We show a reduced number and a different pattern of contents in tweets about psychosis compared with control diseases. PRT showed a predominance of nonmedical content with increased frequencies of misuse and pejorative tone. However, the medical content of PRT showed high scientific appropriateness aimed toward prevention.

The contents of traditional communication media and new internet social media reflect the interests of society. However, certain barriers and a lack of attention towards mental disorders have been previously observed. The objective of this study is to measure the relevance of influential American mainstream media outlets for the distribution of psychiatric information and the interest generated in these topics among their Twitter followers. We investigated tweets generated about mental health conditions and diseases among 15 mainstream general communication media outlets in the United States of America between January 2007 and December 2016. Our study strategy focused on identifying several psychiatric terms of primary interest. The number of retweets generated from the selected tweets was also investigated. As a control, we examined tweets generated about the main causes of death in the United States of America, the main chronic neurological degenerative diseases, and HIV. In total, 13,119 tweets about mental health disorders sent by the American mainstream media outlets were analyzed. The results showed a heterogeneous distribution but preferential accumulation for a select number of conditions. Suicide and gender dysphoria accounted for half of the number of tweets sent. Variability in the number of tweets related to each control disease was also found (5998). The number of tweets sent regarding each different psychiatric or organic disease analyzed was significantly correlated with the number of retweets generated by followers (1,030,974 and 424,813 responses to mental health disorders and organic diseases, respectively). However, the probability of a tweet being retweeted differed significantly among the conditions and diseases analyzed. Furthermore, the retweeted to tweet ratio was significantly higher for psychiatric diseases than for the control diseases (odds ratio 1.11, CI 1.07-1.14; P<.001). American mainstream media outlets and the general public demonstrate a preferential interest for psychiatric diseases on Twitter. The heterogeneous weights given by the media outlets analyzed to the different mental health disorders and conditions are reflected in the responses of Twitter followers.

Environmental conditions profoundly influence cognitive development, particularly during early life. Transcriptional and epigenetic mechanisms may serve as molecular substrates for the lasting effects of environmental enrichment (EE) and impoverishment (IE) on cognitive abilities and hippocampal function. However, the specific gene programs driving these changes remain largely unknown. In this study using female mice, EE and IE produced opposite effects on cognitive performance. By combining hippocampal microdissection and genetic tagging of neuronal nuclei with genome-wide analyses of gene expression, chromatin accessibility, histone acetylation, and DNA methylation, we uncovered profound differences in the transcriptional and epigenetic profiles of CA1 pyramidal neurons and dentate gyrus (DG) granule neurons. These analyses revealed cell type-specific genomic changes induced by EE and IE, highlighting distinct patterns of neuroadaptation within each population. This multiomic screen pinpointed the activity-regulated transcription factor AP-1 as a crucial mediator of neuroadaptation to conditions during early life in both cell types, albeit through distinct downstream mechanisms. Conditional deletion of Fos , a core AP-1 subunit, in excitatory neurons hampered EE-induced cognitive enhancement, further underscoring the pivotal role of this transcription factor in neuroadaptation. Early experiences shape cognition. Here, authors show that early environmental enrichment or deprivation alters cognition in mice, linked to gene expression and chromatin changes in hippocampal excitatory neurons, with AP-1 as a key regulator.

Transcriptional dysregulation in Huntington’s disease (HD) affects the expression of genes involved in survival and neuronal functions throughout the progression of the pathology. In recent years, extensive research has focused on epigenetic and chromatin-modifying factors as a causative explanation for such dysregulation, offering attractive targets for pharmacological therapies. In this work, we extensively examined the gene expression profiles in the cortex, striatum, hippocampus and cerebellum of juvenile R6/1 and N171-82Q mice, models of rapidly progressive HD, to retrieve the early transcriptional signatures associated with this pathology. These profiles were largely consistent across HD datasets, contained tissular and neuronal-specific genes and showed significant correspondence with the transcriptional changes in mouse strains deficient for epigenetic regulatory genes. The most prominent cases were the conditional knockout of the lysine acetyltransferase CBP in post-mitotic forebrain neurons, the double knockout of the histone methyltransferases Ezh1 and Ezh2, components of the polycomb repressor complex 2 (PRC2), and the conditional mutants of the histone methyltransferases G9a (Ehmt2) and GLP (Ehmt1). Based on these observations, we propose that the neuronal epigenetic status is compromised in the prodromal stages of HD, leading to an altered transcriptional programme that is prominently involved in neuronal identity.