Early Life Events Research Articles

Intestinal Immune Development Is Accompanied by Temporal Deviation in Microbiota Composition of Newly Hatched Pigeon Squabs.

ABSTRACTIdentifying the interaction between intestinal mucosal immune system development and commensal microbiota colonization in neonates is of paramount importance for understanding how early life events affect resistance to disease later in life. However, knowledge about this interaction during the early posthatch development period in altrices is limited. To fill this gap, samples of intestinal content and tissue were collected from newly hatched pigeon squabs at four time points (days 0, 7, 14, and 21) for microbial community analysis and genome-wide transcriptome profiling, respectively. We show that the first week after hatching seems to be the critical window for ileal microbiota colonization and that a potentially stable microbiota has not yet been well established at 21 days of age. Regional transcriptome differences revealed that the jejunum rather than the ileum plays a crucial role in immunity at both the innate and adaptive levels. In the ileum, temporal deviation in innate immune-related genes mainly occurs in the first week of life and is accompanied by a temporal change in microbiota composition, indicating that the ileal innate mucosal immune system development regulated by microbial colonization occurs mainly in this period. Furthermore, we provide evidence that colonization by Escherichia and Lactobacillus within the first week of life is likely one of the causative factors for the induction of proinflammatory cytokine expression in the ileum. We also demonstrate that cellular adaptive immune responses mediated by Th17 cells following commensal-induced proinflammatory cytokine production in the ileum begin as early as the first week posthatch, but this cellular immunity seems to be less effective in terms of maintaining the inflammatory response balance. Because the induction of high levels of mucosal secretory IgA (SIgA) seems to take approximately 3 weeks, we favor the idea that humoral adaptive immunity might be less active, at least, during the first 2 weeks of life. Our data may help to explain the phenomenon of the occurrence of intestinal infections mainly in the ileum of pigeon squabs during the early posthatch period.IMPORTANCE The pigeon (Columba livia), an altricial bird, is one of the most economically important farmed poultry for table purposes. Identifying the interaction between intestinal mucosal immune system development and commensal microbiota colonization in neonates is of paramount importance for understanding how early life events affect resistance to disease and potential productivity later in life. However, knowledge about this interaction during the early posthatch development period in altricial birds is limited. The study described herein is the first to try to provide insights into this interaction. Our data provide evidence on the mutual relationship between intestinal mucosal immune system development and commensal microbiota colonization in pigeon squabs and may help to explain the phenomenon of the occurrence of intestinal infections mainly in the ileum of pigeon squabs during the early posthatch period.

Associations of Blautia Genus With Early-Life Events and Later Phenotype in the NutriHS.

IntroductionEarly-life events are associated with the risk of obesity and comorbidities later in life. The gut microbiota—whose composition is influenced by genetics and environmental factors—could be involved. Since the microbiota affects metabolism and fat storage, early-life insults could contribute to the occurrence of obesity driven, in part, by microbiota composition. We examined associations of gut bacteria with early-life events, nutritional status, and body composition in the Nutritionist’s Health Study (NutriHS).MethodsA cross-sectional study of 114 female participants examining early-life data, body composition, and biological samples was conducted. Fecal microbiota structure was determined targeting the V4 region of the 16S rRNA gene. Principal coordinates analysis (PCoA) and permutational multivariate analysis of variance (PERMANOVA) were used to test the impact of variables on microbial diversity. Profiles were identified using the Jensen-Shannon divergence matrix and Calinski–Harabasz index. Differential abundance between the categories of exclusive breastfeeding duration and nutritional status was tested using DESeq2.ResultsIn the sample [median age 28 years and body mass index (BMI) 24.5 kg/m2], 2 microbiota profiles driven by the Blautia or Prevotella genus were identified. An estimated 9.1% of the variation was explained by the profiles (p < 0.001), 2.1% by nutritional status (p = 0.004), and 1.8% by exclusive breastfeeding (p = 0.012). The proportion of participants with BMI <25 kg/m2 and who were breastfed for at least 6 months was higher in the Blautia profile (p < 0.05).ConclusionFindings in a Blautia-driven profile of healthy women reinforce that early-life events play a role in defining gut microbiota composition, confirming the importance of exclusive breastfeeding for infant gut colonization in establishing a protective profile against adiposity-related outcomes in adulthood.

The role of maternal factors in epigenetic programming of neurodevelopment

Early life events are potent determinants of vulnerability and resistance to stressors. In many species, including rodents, the mother is the primary mediator of behavioral and physiological responses to stress in offspring during development. Emerging evidence indicates that epigenetic modifications in the brain of developing offspring are associated with the effects of maternal stress as well as individual neural, physiological, and behavioral responses to adversity. I will discuss research in my lab focused on identifying the relevant genomic targets (in the brain and periphery) of maternal stressors that exert long‐term ‘programming’ effects on stress responses. We have approached this question in several ways. First, we have studied ecologically important stressors applied during gestation. Second, we have investigated factors that co‐occur or interact with maternal care, including variations in ambient temperature and offspring genotype, that influence neurodevelopment and later‐life behavior. Third, we have explored direct exposure to maternal dietary stressors across the developmental period on offspring phenotype and genome‐wide epigenetic modifications in offspring brain. Through these investigations we will explore the significance of the maternal environment in neurodevelopment and the role of epigenetic mechanisms in important signaling pathways involved in susceptibility to stress‐related illness.

Neonatal immune challenge influences the microbiota and behaviour in a sexually dimorphic manner

There is comorbidity between anxiety disorders and gastrointestinal disorders, with both linked to adverse early life events. The microbiome gut-brain-axis, a bidirectional communication system, is plastic throughout the neonatal period and is a possible mediator of this relationship. Here, we used a well-established neonatal rodent immune activation model to investigate the long-term effect of neonatal lipopolysaccharide (LPS) exposure on adult behaviour and the relationship to microbiome composition. Wistar rats were injected with LPS (0.05 mg/kg) or saline (equivolume) on postnatal days 3 and 5. In adulthood, behavioural tests were performed to assess anxiety-like behaviour, and microbiota sequencing was performed on stool samples. There were distinctly different behavioural phenotypes for LPS-exposed males and females. LPS-exposed males displayed typical anxiety-like behaviours with significantly decreased social interaction (F(1,22) = 7.576, p = 0.009) and increased defecation relative to saline controls (F(1,23) = 8.623, p = 0.005). LPS-exposed females displayed a different behavioural phenotype with significantly increased social interaction (F(1,22) = 6.094, p = 0.018), and exploration (F(1,24) = 6.359, p = 0.015), compared to saline controls. With respect to microbiota profiling data, Bacteroidota was significantly increased for LPS-exposed females (F(1,14) = 4.931p = 0.035) and Proteobacteria was decreased for LPS-exposed rats of both sexes versus controls (F(1,30) = 4.923p = 0.035). Furthermore, alterations in predicted functional pathways for neurotransmitters in faeces were observed with a decrease in the relative abundance of D-glutamine and D-glutamate metabolism in LPS exposed females compared to control females (p < 0.05). This suggests that neonatal immune activation alters both later life behaviour and adult gut microbiota in sex-specific ways. These findings highlight the importance of sex in determining the impact of neonatal immune activation on social behaviour and the gut microbiota.

Current Evidence and Diverse Perspectives on Attention-Deficit/Hyperactivity Disorder: A Systematic Review

Introduction: ADHD is one of the most common neurodevelopmental disorders in childhood and adolescence. Although the disorder starts to manifest early in childhood, a significant proportion of cases often persists into adulthood. ADHD negatively and significantly impacts social and occupational functioning and academic performance. A number of extant theories and scientific evidence provide insight into the genesis and manifestations of ADHD and the attendant challenges of significant dysfunction that individuals may encounter at home, school, and the workplace. Method: This systematic review was conducted through a literature search for published peer-reviewed articles using standard PRISMA guidelines. The goal of the study was to explore current theories, models, concepts, and risk factors about ADHD in published in peer-reviewed literature,. We made use of use several online databases— including PsycINFO, PubMed, Web of Science, ScienceDirect, and Medline in the process of searching for relevant studies. Relevant peer-reviewed publications since the 1980s when the term Attention-Deficit/Hyperactivity Disorder (ADHD) was introduced in DSM-III-R were included. Non-peer-reviewed publications, including dissertations, editorials, commentaries, and materials published in languages other than English were excluded. Results and Discussion: The results of the review indicated that ADHD is characterized by a behavioral reaction that interferes with personal and social functioning. The factors associated with ADHD fall into several major thematic areas, including genetic and hereditary factors; dietary and nutritional factors; parenting and behavioral factors; adverse early life events, and high-risk environmental factors, crystallized by a number of developmental and behavioral theories. The review also identified a number of extant models and theories that attempt to explain the diverse perspectives associated with ADHD. Conclusion: This study has attempted to identify the major risk factors and diverse models and theories associated with ADHD. The thematic risk factors include genetic and hereditary factors; dietary and nutritional factors; parenting and behavioral factors; adverse early life events, and high-risk environmental factors. The most prominent models identified include the biomedical model and the bio-psycho-social models, the latter being a more holistic approach which aims to treat both the patient and the disease. This review would provide an additional evidence base to individuals, families, and educators to make informed choices and decisions in the best interest of the affected children, including personal growth, healthcare, and medical needs, academic performance, and social skills development.

Early Life Events and Maturation of the Dentate Gyrus: Implications for Neurons and Glial Cells.

The dentate gyrus (DG), an important part of the hippocampus, plays a significant role in learning, memory, and emotional behavior. Factors potentially influencing normal development of neurons and glial cells in the DG during its maturation can exert long-lasting effects on brain functions. Early life stress may modify maturation of the DG and induce lifelong alterations in its structure and functioning, underlying brain pathologies in adults. In this paper, maturation of neurons and glial cells (microglia and astrocytes) and the effects of early life events on maturation processes in the DG have been comprehensively reviewed. Early postnatal interventions affecting the DG eventually result in an altered number of granule neurons in the DG, ectopic location of neurons and changes in adult neurogenesis. Adverse events in early life provoke proinflammatory changes in hippocampal glia at cellular and molecular levels immediately after stress exposure. Later, the cellular changes may disappear, though alterations in gene expression pattern persist. Additional stressful events later in life contribute to manifestation of glial changes and behavioral deficits. Alterations in the maturation of neuronal and glial cells induced by early life stress are interdependent and influence the development of neural nets, thus predisposing the brain to the development of cognitive and psychiatric disorders.

Alcohol Deprivation Differentially Changes Alcohol Intake in Female and Male Rats Depending on Early-Life Stressful Experience.

Experiencing early-life adverse events has enduring effects on individual vulnerability to alcohol abuse and the development of addiction-related behaviors. In rodents, it can be studied using maternal separation (MS) stress. Studies have shown that, depending on the protocol used, MS can affect the mother and pups' behavior and are associated with behavioral alterations later in adulthood, associated with both positive or negative outcomes. However, it is not fully elucidated how MS affects relapse-like behaviors when experienced by female or male individuals. Therefore, the aim of our study was to evaluate the effects of brief and prolonged MS on the alcohol deprivation effect (ADE) in female and male rats. Female and male Wistar rats were exposed to brief (15 min/day) or prolonged (180 min/day) MS from postnatal day (PND) 2 to 10. Later, during adulthood (PND 70), animals were submitted to an ADE protocol. Brief MS exposure prevented the ADE in both females and males, while prolonged MS exposure also prevented the ADE in female rats. Moreover, the ADE was more robust in females when compared to males. In conclusion, we showed that male and female rats are differentially affected by alcohol deprivation periods depending on their early-life experiences.

The Epidemiology of Biliary Atresia: Exploring the Role of Developmental Factors on Birth Prevalence

To identify key epidemiologic factors relevant to fetal development that are associated with biliary atresia. This population-based registry study examined infants born in Texas between 1999 and 2014. Epidemiologic data relevant to fetal development were compared between cases of biliary atresia identified in the Texas Birth Defects Registry (n=305) vs all live births (n=4 689 920), and Poisson regression was used to calculate prevalence ratios (PRs) and 95% CIs. The prevalence of biliary atresia over the study period was 0.65 per 10 000 live births. Biliary atresia waspositively associated with female sex (adjusted PR, 1.68; 95% CI, 1.33-2.12), delivery before 32-37weeks of gestation (adjusted PR, 1.64; 95% CI, 1.18-2.29), delivery before 32weeks of gestation (adjusted PR, 3.85; 95% CI, 2.38-6.22), and non-Hispanic Black vs non-Hispanic White maternal race/ethnicity (adjusted PR, 1.54, 95% CI, 1.06-2.24), while biliary atresia was inversely associated with season of conception in the fall relative to spring (adjusted PR, 0.62; 95% CI, 0.45-0.86). In addition, biliary atresia was associated with maternal diabetes (adjusted PR, 2.34; 95% CI, 1.57-3.48), with a stronger association with pregestational diabetes compared with gestational diabetes. In subgroup analyses, these associations were present in isolated biliary atresia cases that do not have any additional birth defects. Biliary atresia is associated with multiple factors related to fetal development, including pregestational maternal diabetes, female sex, and preterm birth. These associations also were observed in isolated cases of biliary atresia without other malformations or laterality defects. Our results are consistent with early life events influencing the pathogenesis of biliary atresia, and support further studies investigating in utero events to better understand etiology and time of onset.

Low Birth Weight, β-Cell Function and Insulin Resistance in Adults: The Brazilian Longitudinal Study of Adult Health.

BackgroundAdverse intrauterine environment—reflected by low birth weight (LBW)—has been linked to insulin resistance and type 2 diabetes later in life. Whether β-cell function reduction and insulin resistance could be detected even in middle-aged adults without overt diabetes is less investigated. We examined the association of LBW with β-cell function and insulin sensitivity in non-diabetic middle-aged adults from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).MethodsThis is a cross-sectional analysis of 2,634 ELSA-Brasil participants aged between 34 and 59 years, without diabetes. Participants were stratified according to LBW defined as <2.5 kg and their clinical data were compared. HOMA-IR, HOMA-β, HOMA-adiponectin, TyG index, QUICKI and TG/HDL were calculated and their association with LBW were tested using multiple linear regression including adjustments suggested by Directed Acyclic Graphs and propensity score matching was applied.ResultsThe sample (47.4 ± 6.3 years) was composed of 57.5% of women and 9% had LBW. Subjects with LBW and normal-weight reported similar BMI values at the age of 20 years and current BMI was slightly lower in the LBW group. In average, cardiometabolic risk profile and also indexes of β-cell function and insulin sensitivity were within normal ranges. In regression analysis, log-transformed HOMA-β—but not with the other indexes—was associated with LBW (p = 0.014) independent of sex, skin color, prematurity, and family history of diabetes. After applying propensity-score matching in a well-balanced sample, HOMA-AD and TG/HDL indexes were associated with LBW.ConclusionThe association between LBW and insulin sensitivity markers may occur in healthy middle-aged adults before overt glucose metabolism disturbances. Our data are coherent with the detection of early life events consequent with insulin resistance markers that could contribute to the risk of glucose metabolism disturbances.

80 Randel Lectureship: Practical Applications for Developmental Programming of the Bovine Ovary

Abstract Mammalian females are born with a finite supply of follicles within their ovaries that may be related to fertility and reproductive longevity. The number of microscopic follicles in the ovarian cortex is positively correlated to the number of antral follicles. In cattle, the number of antral follicles can be determined by ultrasonographic examination of the ovaries, is repeatable within a female, and has a moderate heritability. Studies in rodents suggest that nutritional status early in life can alter structure and function of the ovarian reserve, resulting in changes in follicle numbers, estrous cycle parameters, and reproductive longevity. This raises questions about how early life events might influence the ovarian reserve and reproductive performance in bovine females. A central hypothesis of our research is that the number of follicles that a heifer has when entering her first breeding season is influenced by external factors such as maternal nutrition during pregnancy, maternal stress during pregnancy, peri-pubertal nutrition, and health events. Understanding how these factors influence the structure and function of the ovarian reserve in replacement heifers may allow us to translate this knowledge into management practices that developmentally program the bovine ovary prior to the first breeding season to improve reproductive performance in the cow herd. Accomplishing this is made difficult because our understanding of the mechanisms controlling pre-antral follicle development in cattle is limited and growth of pre-antral follicles is occurring at the microscopic level within the ovarian cortex where it is difficult to monitor changes in real time. There has been some success, but variation in response across studies indicates that further research to understand the causes of this variation is required before we will be able to apply developmental programming in beef production systems to improve ovarian function in replacement heifers. USDA is an equal opportunity provider and employer.

Early postnatal handling alters social behavior, learning, and memory of pre- and postnatal VPA-induced rat models of autism in a context-based manner

Early life events are known to greatly affect brain development, cortical neurogenesis, and Hypothalamic-pituitary-adrenal activity. Mainly characterized by impairment in social communication, language, and cognitive development, autism spectrum disorder (ASD) refers to a class of neuropsychiatric disorders with numerous genetic and environmental risk factors. In the early handling (EH) method, daily separation of infants from their mother, physical touching, and exposure to a new environment occur. Here, we studied the effect of EH on Social interaction, learning, and memory in rats exposed pre-or post-natally to valproic acid (VPA). Gestational VPA exposure (600 mg/kg) led to some severe autistic-like traits, more notable in the social behavior of the male sex, along with unchanged to partially altered spatial learning and memory function and reduced avoidance memory. In comparison, while causing a sex-dependent increase in spatial memory, subcutaneous injection of VPA (400 mg/kg) in infancy resulted in limited adverse autistic features, including a decrease in males’ social preference, as well as reduced avoidance memory. The results indicated that neonatal handling significantly improved multiple social behavior and memory deficits in prenatally injected rats. In contrast, EH in rats receiving postnatal VPA elicited a restricted advantage on social novelty tendency; while negatively affecting some other social behavior criteria and spatial learning of males and encouraging sex-dependent repetitive behaviors in the social setting. The controversial influence of postnatal handling on juvenile rats of postnatal VPA treatment vs. prenatal VPA treatment opens up the potential for future research on the context-based consequence of early-life handling stress using different behavioral tasks and to benefit therapeutic procedures through understanding the sex- and age-specific neurobiology of short-term environmental manipulation in animal models of autism.

Do partnership dissolutions and living alone affect systemic chronic inflammation? A cohort study of Danish adults

BackgroundPartnership breakups and living alone are associated with several adverse health outcomes. The aim of this study, carried out in Denmark, is to investigate whether accumulated numbers of divorces/partnership breakups...

Experiences of Patients With Hashimoto Thyroiditis Through the Lens of Compassion

Hashimoto thyroiditis (HT) is an autoimmune disease affecting mainly middle-aged women. Hormonal replacement is the most common therapy; however, it tackles only the functionality of the thyroid and not the autoimmunity components. Thus, patients experience persistent somatic and psychological symptoms, thereby affecting their quality of life. The cause of HT remains uncertain. Primary evidence suggests that adverse experiences in childhood are associated with autoimmune disease manifestation in adulthood; therefore, the effect of early adverse events on disease course needs to be explored. This paper explored patients’ early life events and everyday experiences through the lens of compassion, as defined in compassion-focused therapy (CFT). In this study, nine participants were interviewed, and the transcribed interviews were analyzed using Thematic Analysis. Qualitative analysis indicated that patients exhibited increased psychological distress and a lack of understanding from others. Common patterns of experiences and behaviors were identified, such as the lack of compassion and affiliation between significant others and themselves. Therefore, including psychological care in the therapeutic process of HT would improve patients’ well-being and quality of life. In particular, cultivating compassion could be a promising strategy for disease prevention and the healthy functioning of patients.

Vulnerability to early stressful life events: The moderating role of HOMER1 gene in the gene × environment interaction

ABSTRACT To explore the curvilinear relationship between early stressful life events and future-oriented coping and whether the HOMER1 (rs7713917) polymorphism can moderate the relationship between early life stress and two types of future-oriented coping, 14,675 Han Chinese people were surveyed. The relationship between the number of early stressful life events and future-oriented coping adhered to a quadratic curve. HOMER1 polymorphisms moderated the relationship between the impact of early life stress and preventive coping (β = −0.02, 95% CI [−0.03, −0.01], p = 0.010), which was different from that of proactive coping (β = −0.01, 95% CI [−0.02, 0.01], p = 0.073). Individuals with the AA genotype who experienced a high impact of early life stress were more likely to use preventive coping compared with those who experienced a low level of early life stress, but they showed no difference in their proactive coping strategies. In contrast, individuals with the GA/GG genotype displayed higher vulnerability to environmental changes.

Early Life Events and Path to Opiates Addiction

Early Life Events and Path to Opiates Addiction

Unpacking determinants and consequences of food insecurity for insulin resistance among people living with HIV: Conceptual framework and protocol for the NOURISH-OK study.

Background:Over the past four decades, advances in HIV treatment have contributed to a longer life expectancy for people living with HIV (PLWH). With these gains, the prevention and management of chronic co-morbidities, such as diabetes, are now central medical care goals for this population. In the United States, food insecurity disproportionately impacts PLWH and may play a role in the development of insulin resistance through direct and indirect pathways. The Nutrition to Optimize, Understand, and Restore Insulin Sensitivity in HIV for Oklahoma (NOURISH-OK) will use a novel, multi-level, integrated framework to explore how food insecurity contributes to insulin resistance among PLWH. Specifically, it will explore how food insecurity may operate as an intermediary risk factor for insulin resistance, including potential linkages between upstream determinants of health and downstream consequences of poor diet, other behavioral risk factors, and chronic inflammation.Methods/design:This paper summarizes the protocol for the first aim of the NOURISH-OK study, which involves purposeful cross-sectional sampling of PLWH (n=500) across four levels of food insecurity to test our conceptual framework. Developed in collaboration with community stakeholders, this initial phase involves the collection of anthropometrics, fasting blood samples, non-blood biomarkers, 24-hour food recall to estimate the Dietary Inflammatory Index (DII®) score, and survey data. A 1-month, prospective observational sub-study (total n=100; n=25 for each food security group) involves weekly 24-hour food recalls and stool samples to identify temporal associations between food insecurity, diet, and gut microbiome composition. Using structural equation modeling, we will explore how upstream risk factors, including early life events, current discrimination, and community food access, may influence food insecurity and its potential downstream impacts, including diet, other lifestyle risk behaviors, and chronic inflammation, with insulin resistance as the ultimate outcome variable. Findings from these analyses of observational data will inform the subsequent study aims, which involve qualitative exploration of significant pathways, followed by development and testing of a low-DII® food as medicine intervention to reverse insulin resistance among PLWH (ClinicalTrials.gov Identifier: NCT05208671).Discussion:The NOURISH-OK study will address important research gaps to inform the development of food as medicine interventions to support healthy aging for PLWH.

BASF, Dow feel supply chain impact

Early life events have special importance in the development as postnatal environmental alterations may permanently affect the lifetime vulnerability to diseases. For the interpretation of the long-term consequences it is important to understand the immediate effects. As the role of vasopressin in hypothalamic-pituitary-adrenal axis regulation as well as in affective disorders seem to be important we addressed the question whether the congenital lack of vasopressin will modify the stress reactivity of the pups and will influence the later consequences of single 24 h maternal deprivation (MD) on both stress-reactivity and stress-related behavioral changes.Vasopressin-producing (di/+) and deficient (di/di) Brattleboro rat were used. In 10-day-old pups MD induced a remarkable corticosterone rise in both genotypes without adrenocorticotropin (ACTH) increase in di/di rats. Studying the later consequences at around weaning (25–35-day-old rats) we found somatic and hormonal alterations (body weight reduction, dysregulation of the stress axis) which were not that obvious in di/di rats. The more anxious state of MD rats was not detectable in di/di rats both at weaning and in adulthood (7–12-week-old).The lack of vasopressin abolished all chronic stress and anxiety-like tendencies both at weaning and in adulthood probably as a consequence of reduced ACTH rise immediately after MD in pups. This finding suggests that postnatal stress-induced ACTH rise may have long-term developmental consequences.

Early-life thermal stress mediates long-term alterations in hypothalamic microglia.

Stressful environmental events in early life have long-lasting consequences on later stress responses. We previously showed that heat conditioning of 3-day-old chicks during the critical period of heat-response development leads to heat vulnerability later in life. Here we assessed the role of early-life heat stress on the inflammatory response in the chick anterior hypothalamus (AH), focusing on hypothalamic microglia. We identified the microglial cell population in the chick AH using anti-KUL01 and anti-CD45 antibodies. Specific microglial features were also confirmed by expression of their signature genes. Under normal environmental conditions, hypothalamic microglia isolated from lipopolysaccharide (LPS)-injected chicks displayed a classical activated proinflammatory profile accompanied by a decreased homeostatic signature, demonstrating similarity of immune response with mammalian microglial cells. In accordance with our previous observations, conditioning of 3-day-old chicks under high ambient temperature decreased the number of newborn cells in the AH, among them microglial precursors. Although heat exposure did not affect microglial cell viability, it had a long-term impact on LPS-induced inflammatory response. Exposure to harsh heat led to heat vulnerability, and attenuated recruitment of peripheral monocytes and T cells into the AH following LPS challenge. Moreover, heat conditioning altered microglial reactivity, manifested as suppressed microglial activation in response to LPS. Innate immune memory developed by heat conditioning might underlie suppression of the microglial response to LPS challenge. We describe alterations in genome-wide CpG methylation profile of hypothalamic microglia, demonstrating probable epigenetic involvement in the reprogramming of microglial function, leading to heat-induced inflammatory cross-tolerance.

Association between bilateral oophorectomy and cognitive decline in older women from the Baltimore Longitudinal Study of Aging

AbstractBackgroundNearly two‐thirds of individuals with Alzheimer’s disease (AD) are women, and the lifetime risk for AD is twice as high in women compared to men at age 45 (Alzheimer’s Association, 2019). Despite this increased prevalence, little is known about why more women develop AD. Early life events affecting 17β‐estradiol (E2) may be a potential mechanism behind this sex difference. E2 and/or ovarian loss leads to cognitive decline and neurodegeneration, which is mitigated with E2 (Gervais et al., 2020; Kantarci et al., 2018; Zeydan et al., 2019). Further, women with bilateral oophorectomy have an increased risk of AD in later life (Rocca et al., 2007). However, little is known about the long‐term trajectories of cognitive change post‐oophorectomy.MethodThe current study investigated cognitive decline over time in older women with bilateral oophorectomy (BO; n = 30; total visits = 131) prior to age 45 compared to spontaneously menopausal (SM; n = 61; total visits = 277) women from the Baltimore Longitudinal Study of Aging (BLSA; Shock et al., 1984). All participants were free of any dementia and completed a variety of demographic and cognitive assessments. Each eligible BO participant was age‐matched at a 1:2 ratio with a SM participant. Data were analyzed using linear mixed‐effects models in R 3.6.1 (R Core Team, 2019).ResultParticipants completed an average of four visits over 11‐years, and ranged in age from 52‐91 years. Our analyses revealed the BO group recalled significantly less words on the California Verbal Learning Test and made significantly more errors on the Benton Visual Retention Test over time than the SM group. Additionally, the BO group had poorer Digits Backward and Letter Fluency performance over time compared to the SM group.ConclusionResults demonstrate an association between BO prior to age 45 and greater longitudinal decline in executive function, verbal memory, visual memory, and working memory performance compared to age‐matched, spontaneously menopausal women. This is the first study to evaluate continuous cognitive decline post‐oophorectomy from midlife to older age, and suggests that even in normal aging, the early loss of E2 via BO may confer long‐lasting effects on cognition spanning decades of life.

Split-Second Unlearning: Developing a Theory of Psychophysiological Dis-ease.

Psychophysiological “stress” underpins many conditions including anxiety, depression, phobias, chronic fatigue syndrome and non-specific musculoskeletal pain such as fibromyalgia. In this article we develop an understanding of chronic psychophysiological stress from a psychological educational perspective, by drawing on supporting evidence that significant emotional events in early life (traumatic and benign) can influence health and well-being later in life. We suggest that traumatic events instigate psychophysiological “stress” responses and the formation of emotional memory images (EMIs) within very short time frames, i.e., “split-second learning.” Once formed these emotional memories are triggered in daily living “re-playing” psychophysiological stress responses, resulting in chronic psychophysiological “dis-ease.” We describe a novel therapeutic approach to scan clients for mannerisms signifying a subconscious “freeze-like” stress response that involves the client as a curious observer within their own experience, feeding back the non-verbal cues as they arrive in the moment. By breaking down the observable fragments of their split-second Pavlovian response to the trigger, clients can detach their EMI from the psychophysiology stress response, i.e., “split-second unlearning.” Our split-second unlearning model recognizes the EMI as a barrier to moving forward and needs to be unlearned before the client can become naturally adaptive again. We argue that this approach places the client at the center of the work without the need of getting bogged down in a life-long narrative.