Binge-Pattern Alcohol Exposure during Puberty Induces Long-Term Changes in HPA Axis Reactivity

Adolescence is a dynamic and important period of brain development however, little is known about the long-term neurobiological consequences of alcohol consumption during puberty. Our previous studies showed that binge-pattern ethanol (EtOH) treatment during pubertal development negatively dysregulated the responsiveness of the hypothalamo-pituitary-adrenal (HPA) axis, as manifested by alterations in corticotrophin-releasing hormone (CRH), arginine vasopressin (AVP), and corticosterone (CORT) during this time period. Thus, the primary goal of this study was to determine whether these observed changes in important central regulators of the stress response were permanent or transient. In this study, juvenile male Wistar rats were treated with a binge-pattern EtOH treatment paradigm or saline alone for 8 days. The animals were left undisturbed until adulthood when they received a second round of treatments consisting of saline alone, a single dose of EtOH, or a second binge-pattern treatment paradigm. The results showed that pubertal binge-pattern EtOH exposure induced striking long-lasting alterations of many HPA axis parameters. Overall, our data provide strong evidence that binge-pattern EtOH exposure during pubertal maturation has long-term detrimental effects for the healthy development of the HPA axis

Identification of CIITA Regulated Genetic Module Dedicated for Antigen Presentation

The class II trans-activator CIITA is a transcriptional co-activator required for the expression of Major Histocompatibility Complex (MHC) genes. Although the latter function is well established, the global target-gene specificity of CIITA had not been defined. We therefore generated a comprehensive list of its target genes by performing genome-wide scans employing four different approaches designed to identify promoters that are occupied by CIITA in two key antigen presenting cells, B cells and dendritic cells. Surprisingly, in addition to MHC genes, only nine new targets were identified and validated by extensive functional and expression analysis. Seven of these genes are known or likely to function in processes contributing to MHC-mediated antigen presentation. The remaining two are of unknown function. CIITA is thus uniquely dedicated for genes implicated in antigen presentation. The finding that CIITA regulates such a highly focused gene expression module sets it apart from all other transcription factors, for which large-scale binding-site mapping has indicated that they exert pleiotropic functions and regulate large numbers of genes

Using direct observations on multiple occasions to measure household food availability among low-income Mexicano residents in Texas colonias

BACKGROUND: It has been recognized that the availability of foods in the home are important to nutritional health, and may influence the dietary behavior of children, adolescents, and adults. It is therefore important to understand food choices in the context of the household setting. Considering their importance, the measurement of household food resources becomes critical.Because most studies use a single point of data collection to determine the types of foods that are present in the home, which can miss the change in availability within a month and when resources are not available, the primary objective of this pilot study was to examine the feasibility and value of conducting weekly in-home assessments of household food resources over the course of one month among low-income Mexicano families in Texas colonias. METHODS: We conducted five in-home household food inventories over a thirty-day period in a small convenience sample; determined the frequency that food items were present in the participating households; and compared a one-time measurement with multiple measurements.After the development and pre-testing of the 252-item culturally and linguistically- appropriate household food inventory instrument that used direct observation to determine the presence and amount of food and beverage items in the home (refrigerator, freezer, pantry, elsewhere), two trained promotoras recruited a convenience sample of 6 households; administered a baseline questionnaire (personal info, shopping habits, and food security); conducted 5 in-home assessments (7-day interval) over a 30-day period; and documented grocery shopping and other food-related activities within the previous week of each in-home assessment. All data were collected in Spanish. Descriptive statistics were calculated for mean and frequency of sample characteristics, food-related activities, food security, and the presence of individual food items. Due to the small sample size of the pilot data, the Friedman Test and Kendall's W were used to assess the consistency of household food supplies across multiple observations. RESULTS: Complete data were collected from all 6 Mexicano women (33.2y +/- 3.3; 6.5 +/- 1.5 adults/children in household (HH); 5 HH received weekly income; and all were food insecure. All households purchased groceries within a week of at least four of the five assessments. The weekly presence and amounts of fresh and processed fruits and vegetables, dairy, meats, breads, cereals, beverages, and oils and fats varied. Further, the results revealed the inadequacy of a one-time measurement of household food resources, compared with multiple measures. The first household food inventory as a one-time measure would have mistakenly identified at least one-half of the participant households without fresh fruit, canned vegetables, dairy, protein foods, grains, chips, and sugar-sweetened beverages. CONCLUSIONS: This study highlights the value of documenting weekly household food supplies, especially in households where income resources may be more volatile. Clearly, the data show that a single HFI may miss the changes in availability--presence and amount--that occur among low-income Mexicano households who face challenges that require frequent purchase of foods and beverages. Use of multiple household food inventories can inform the development and implementation of nutrition-related policies and culturally sensitive nutrition education programs

Sex-specific disruption of murine midbrain astrocytic and dopaminergic developmental trajectories following antenatal GC treatment

The mammalian midbrain dopaminergic systems arising in the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) are critical for coping behaviours and are implicated in neuropsychiatric disorders where early life challenges comprise significant risk factors. Here, we aimed to advance our hypothesis that glucocorticoids (GCs), recognised key players in neurobiological programming, target development within these systems, with a novel focus on the astrocytic population. Mice received antenatal GC treatment (AGT) by including the synthetic GC, dexamethasone, in the mothers' drinking water on gestational days 16-19; controls received normal drinking water. Analyses of regional shapes and volumes of the adult SNc and VTA demonstrated that AGT induced long-term, dose-dependent, structural changes that were accompanied by profound effects on astrocytes (doubling/tripling of numbers and/or density). Additionally, AGT induced long-term changes in the population size and distribution of SNc/VTA dopaminergic neurons, confirming and extending our previous observations made in rats. Furthermore, glial/neuronal structural remodelling was sexually dimorphic and depended on the AGT dose and sub-region of the SNc/VTA. Investigations within the neonatal brain revealed that these long-term organisational effects of AGT depend, at least in part, on targeting perinatal processes that determine astrocyte density and programmed cell death in dopaminergic neurons. Collectively, our characterisation of enduring, AGT-induced, sex-specific cytoarchitectural disturbances suggests novel mechanistic links for the strong association between early environmental challenge (inappropriate exposure to excess GCs) and vulnerability to developing aberrant behaviours in later life, with translational implications for dopamine-associated disorders (such as schizophrenia, ADHD, autism, depression), which typically show a sex bia