Depression is a complex disorder that takes an enormous toll on individual health. As affected individuals display a wide variation in their clinical symptoms, the precise neural mechanisms ...underlying the development of depression remain elusive. Although it is impossible to phenocopy every symptom of human depression in rodents, the preclinical field has had great success in modeling some of the core affective and neurovegetative depressive symptoms, including social withdrawal, anhedonia, and weight loss. Adaptations in select cell populations may underlie these individual depressive symptoms and new tools have expanded our ability to monitor and manipulate specific cell types. This review outlines some of the most recent preclinical discoveries on the molecular and neurophysiological mechanisms in reward circuitry that underlie the expression of behavioral constructs relevant to depressive symptoms.
Nucleus accumbens dopamine 1 receptor medium spiny neurons (D1-MSNs) play a critical role in the development of depression-like behavior in mice. Social defeat stress causes dendritic morphological ...changes on this MSN subtype through expression and activation of early growth response 3 (EGR3) and the Rho guanosine triphosphatase RhoA. However, it is unknown how RhoA inhibition affects electrophysiological properties underlying stress-induced susceptibility.
A novel RhoA-specific inhibitor, Rhosin, was used to inhibit RhoA activity following chronic social defeat stress. Whole-cell electrophysiological recordings of D1-MSNs were performed to assess synaptic and intrinsic consequences of Rhosin treatment on stressed mice. Additionally, recorded cells were filled and analyzed for their morphological properties.
We found that RhoA inhibition prevents both D1-MSN hyperexcitability and reduced excitatory input to D1-MSNs caused by social defeat stress. Nucleus accumbens–specific RhoA inhibition is capable of blocking susceptibility caused by D1-MSN EGR3 expression. Lastly, we found that Rhosin enhances spine density, which correlates with D1-MSN excitability, without affecting overall dendritic branching.
These findings demonstrate that pharmacological inhibition of RhoA during stress drives an enhancement of total spine number in a subset of nucleus accumbens neurons that prevents stress-related electrophysiological deficits and promotes stress resiliency.
Stress alters the structure and function of brain reward circuitry and is an important risk factor for developing depression. In the nucleus accumbens (NAc), structural and physiological plasticity ...of medium spiny neurons (MSNs) have been linked to increased stress-related and depression-like behaviors. NAc MSNs have opposing roles in driving stress-related behaviors that is dependent on their dopamine receptor expression. After chronic social defeat stress, NAc MSNs exhibit increased dendritic spine density. However, it remains unclear if the dendritic spine plasticity is MSN subtype specific. Here we use viral labeling to characterize dendritic spine morphology specifically in dopamine D2 receptor expressing MSNs (D2-MSNs). After chronic social defeat, D2-MSNs exhibit increased spine density that is correlated with enhanced social avoidance behavior. Together, our data indicate dendritic spine plasticity is MSN subtype specific, improving our understanding of structural plasticity after chronic stress.
Research is limited on added sugars in school meals and children's dietary intakes after the 2015-2020 Dietary Guidelines for Americans (DGA) recommended that added sugars be limited to less than 10% ...of total calories. This analysis uses data from the School Nutrition and Meal Cost Study (SNMCS) to examine levels of added sugars in: (1) school meals and (2) children's dietary intakes at breakfast, lunch, and over 24 h on school days. SNMCS data were collected in the 2014-2015 school year after updated nutrition standards for school meals were implemented. Most schools exceeded the DGA limit for added sugars at breakfast (92%), while 69% exceeded the limit at lunch. The leading source of added sugars in school meals (both breakfasts and lunches) was flavored skim milk. More than 62% of children consumed breakfasts that exceeded the DGA limit, and almost half (47%) consumed lunches that exceeded the limit. Leading sources of added sugars in the breakfasts consumed by children were sweetened cold cereals and condiments and toppings; leading sources of added sugars in children's lunches were flavored skim milk and cake. Over 24 h, 63% of children exceeded the DGA limit. These findings show that school meals and children's dietary intakes are high in added sugars relative to the DGA limit and provide insights into the types of foods that should be targeted in order to decrease levels of added sugars.
Chronic stress can increase the risk of developing a substance use disorder in vulnerable individuals. Numerous models have been developed to probe the underlying neurobiological mechanisms, however, ...most prior work has been restricted to male rodents, conducted only in rats, or introduces physical injury that can complicate opioid studies. Here we sought to establish how chronic psychosocial stress influences fentanyl consumption in male and female C57BL/6 mice. We used chronic social defeat stress (CSDS), or the modified vicarious chronic witness defeat stress (CWDS), and used social interaction to stratify mice as stress-susceptible or resilient. We then subjected mice to a 15 days fentanyl drinking paradigm in the home cage that consisted of alternating forced and choice periods with increasing fentanyl concentrations. Male mice susceptible to either CWDS or CSDS consumed more fentanyl relative to unstressed mice. CWDS-susceptible female mice did not differ from unstressed mice during the forced periods, but showed increased preference for fentanyl over time. We also found decreased expression of nucleus accumbens Rho GTPases in male, but not female mice following stress and fentanyl drinking. We also compare fentanyl drinking behavior in mice that had free access to plain water throughout. Our results indicate that stress-sensitized fentanyl consumption is dependent on both sex and behavioral outcomes to stress.
Prior research has shown that participation in the United States' National School Lunch Program (NSLP) is associated with consuming higher-quality lunches and diets overall, but little is known about ...differences by income and race/ethnicity. This analysis used 24 h dietary recall data from the School Nutrition and Meal Cost Study to examine how NSLP participation affects the diet quality of students in different income and racial/ethnic subgroups. Diet quality at lunch and over 24 h was assessed using the Healthy Eating Index (HEI)-2010, where higher scores indicate higher-quality intakes. HEI-2010 scores for NSLP participants and nonparticipants in each subgroup were estimated, and two-tailed
-tests were conducted to determine whether participant-nonparticipant differences in scores within each subgroup were statistically significant. NSLP participants' lunches received significantly higher total HEI-2010 scores than those of nonparticipants for lower-income, higher-income, non-Hispanic White, and non-Hispanic Black students, suggesting that participating in the NSLP helps most students consume healthier lunches. These significantly higher total scores for participants' lunch intakes persisted over 24 h for higher-income students and non-Hispanic White students but not for lower-income students or students of other races/ethnicities. For NSLP participants in all subgroups, the nutritional quality of their 24 h intakes was much lower than at lunch, suggesting that the positive influence of the NSLP on their overall diet quality was negatively influenced by foods consumed the rest of the day (outside of lunch).
The potency of the synthetic opioid fentanyl and its increased clinical availability has led to the rapid escalation of use in the general population, increased recreational exposure, and ...subsequently opioid-related overdoses. The wide-spread use of fentanyl has, consequently, increased the incidence of
exposure to the drug, but the long-term effects of this type of developmental exposure are not yet understood. Opioid use has also been linked to reduced mitochondrial copy number in blood in clinical populations, but the link between this peripheral biomarker and genetic or functional changes in reward-related brain circuitry is still unclear. Additionally, mitochondrial-related gene expression in reward-related brain regions has not been examined in the context of fentanyl exposure, despite the growing literature demonstrating drugs of abuse impact mitochondrial function, which subsequently impacts neuronal signaling. The current study uses exposure to fentanyl via dam access to fentanyl drinking water during gestation and lactation as a model for developmental drug exposure. This perinatal drug-exposure is sufficient to impact mitochondrial copy number in circulating blood leukocytes, as well as mitochondrial-related gene expression in the nucleus accumbens (NAc), a reward-related brain structure, in a sex-dependent manner in adolescent offspring. Specific NAc gene expression is correlated with both blood mitochondrial copy number and with anxiety related behaviors dependent on developmental exposure to fentanyl and sex. These data indicate that developmental fentanyl exposure impacts mitochondrial function in both the brain and body in ways that can impact neuronal signaling and may prime the brain for altered reward-related behavior in adolescence and later into adulthood.
Brain-derived neurotrophic factor (BDNF) has a critical role in stress response including neuropsychiatric disorders that are precipitated by stress, such as major depressive disorder (MDD). BDNF ...acts through its full-length BDNF receptor tyrosine kinase B (TrkB) to trigger a pro-plasticity effect. In contrast, the truncated isoform of the BDNF receptor (TrkB.t1) triggers an anti-plasticity effect. In stress outcomes, BDNF acting in the hippocampus has a stress resilience effect, and, inversely, in the nucleus accumbens (NAc), BDNF acts as a stress susceptible molecule. It is unknown if BDNF-TrkB acts on a specific NAc projection neuron, i.e., medium spiny neuron (MSN or spiny projection neuron), a subtype in stress outcomes. To determine this, we performed chronic social or vicarious witness defeat stress (CSDS or CWDS) in mice expressing TrkB.t1 in dopamine receptor 1 or 2 containing MSNs (D1- or D2-MSNs). Our results showed that TrkB.t1 overexpression in NAc D2-MSNs prevented the CSDS-induced social avoidance or other stress susceptible behaviors in male and female mice. We further showed that this overexpression in D2-MSNs blocked stress susceptible behavior induced by intra-NAc BDNF infusion. In contrast, our results demonstrate that overexpression of TrkB.t1 on NAc D1-MSNs facilitates the SDS susceptible behaviors. Our study provides enhanced details into the NAc cell subtype role of BDNF-TrkB signaling in stress outcomes.
Abstract only
The National School Lunch Program (NSLP) serves lunches to 32 million children on an average school day. An ongoing goal of the program is to better align school meals with dietary ...practices recommended in the
Dietary Guidelines for Americans
. The USDA Food Patterns translate the 2010
Dietary Guidelines
into daily amounts of nutrient‐dense foods to eat from five food groups and their subgroups, as well as healthy amounts of oils and limits on calories from solid fats and added sugars (SoFAS). One objective of SNDA‐IV was to assess for the first time the potential contribution of school meals to daily food intakes recommended in USDA's Food Patterns. Between January and June 2010, school foodservice managers in a national sample of schools completed a detailed menu survey for one week. Food items reported were linked to the MyPyramid Equivalents Database and average amounts of Food Pattern food groups available in NSLP lunches were compared with recommendations for school‐age children. On average, lunches offered one‐third or more of recommended amounts of fruit, grains, dairy foods, and oils but were low in whole grains and high in calories from SoFAS. Leading sources of SoFAS calories included flavored milk, baked desserts, and pizza/pizza products. These findings provide an important baseline against which recent regulatory changes in the NSLP can be assessed. Research supported by the USDA, Food and Nutrition Service.
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