Chronic stress alters neuropeptide Y signaling in the bed nucleus of the stria terminalis in DBA/2J but not C57BL/6J mice

Numerous rodent and human studies have demonstrated that neuropeptide Y (NPY) is involved in the regulation of anxiety-related behaviors. In this study, we examined whether there were differences in NPY signaling between two inbred mouse strains (C57BL/6J and DBA/2J) that exhibit divergent basal and stress-induced anxiety phenotypes. We focused on the bed nucleus of the stria terminals (BNST), a structure in the extended amygdala that is important for the regulation of anxiety-like behavior and contains NPY receptors. While results from whole-cell voltage-clamp recordings and immunofluorescence histochemistry revealed no significant basal differences in NPY signaling or NPY and NPY Y2 receptor (Y2R) expression in the BNST, these measures were differentially altered by chronic restraint stress. Ten days of chronic restraint stress increased basal GABAergic transmission and decreased NPY’s ability to inhibit evoked GABAergic transmission in the dorsolateral BNST (dlBNST) via Y2R in DBA/2J, but not C57BL/6J, mice. Additionally, restraint stress increased NPY and Y2R expression across subregions of the BNST of DBA/2J mice 24 hrs after the last stress exposure, but no changes were observed in C57BL/6J mice. Together, these results suggest that chronic restraint stress engages the NPY system and alters NPY modulation of inhibitory transmission in the dlBNST of DBA/2J mice, but not C57BL/6J mice, which may be related to increased expression of anxiety-related behaviors in this strain

Central Neuropeptide Y Modulates Binge-Like Ethanol Drinking in C57BL/6J Mice via Y1 and Y2 Receptors

Frequent binge drinking has been linked to heart disease, high blood pressure, type 2 diabetes, and the development of ethanol dependence. Thus, identifying pharmaceutical targets to treat binge drinking is of paramount importance. Here we employed a mouse model of binge-like ethanol drinking to study the role of neuropeptide Y (NPY). To this end, the present set of studies utilized pharmacological manipulation of NPY signaling, immunoreactivity (IR) mapping of NPY and NPY receptors, and electrophysiological recordings from slice preparations of the amygdala. The results indicated that central infusion of NPY, a NPY Y1 receptor (Y1R) agonist, and a Y2R antagonist significantly blunted binge-like ethanol drinking in C57BL/6J mice (that achieved blood ethanol levels >80 mg/dl in control conditions). Binge-like ethanol drinking reduced NPY and Y1R IR in the central nucleus of the amygdala (CeA), and 24 h of ethanol abstinence after a history of binge-like drinking promoted increases of Y1R and Y2R IR. Electrophysiological recordings of slice preparations from the CeA showed that binge-like ethanol drinking augmented the ability of NPY to inhibit GABAergic transmission. Thus, binge-like ethanol drinking in C57BL/6J mice promoted alterations of NPY signaling in the CeA, and administration of exogenous NPY compounds protected against binge-like drinking. The current data suggest that Y1R agonists and Y2R antagonists may be useful for curbing and/or preventing binge drinking, protecting vulnerable individuals from progressing to the point of ethanol dependence

Exploring parenting stress levels and its predicting factors in parents of children with developmental coordination disorder.

Background: There is evidence that parents of children with neurodevelopmental disorders report higher levels of parenting stress compared to parents of typically developing (TD) children, with more than half of those parents experiencing levels of parenting stress within the clinical range. However, there is very little research on whether parents of children with Developmental Coordination Disorder (DCD) also experience high levels of parenting stress, and, if so, the factors that contribute to this stress. Aim: The current study explored whether parents of children with DCD experience higher levels of parenting stress compared to parents of TD children, and the factors that predict parenting stress in parents of children with DCD. Method: 174 parents of children (ages 5-12) with a diagnosis of DCD and 24 parents of TD children participated in an online survey. Participants completed five questionnaires measuring parenting stress, social support, parenting self-efficacy, the child’s emotional and behavioural problems, and severity of the child’s motor coordination problems. Results: Parents of children with DCD reported experiencing significantly higher levels of parenting stress than parents of TD children. Two-thirds of parents of children with DCD reported experiencing levels of parenting stress within the clinical range. The severity of the child’s emotional and behavioural problems, the level of social support and parenting self-efficacy were found to be significant predictors of parenting stress, but not the severity of the child’s motor difficulties. Discussion: These findings are mostly consistent with research on other neurodevelopmental disorders. They highlight that these parents may be a vulnerable group which requires support from professionals to cope with the demands of caring for their children. The management of behavioural problems, the parent’s self-efficacy, and increasing the level of social support should be considered in the development of tailored interventions for these parents.</p

Internalising symptoms in Developmental Coordination Disorder: A systematic review and meta-analysis

Background: Developmental Coordination Disorder (DCD) affects 5-6% of children. There is growing evidence that DCD is associated with greater levels of internalising symptoms (i.e. depression and anxiety). This is the first systematic review and meta-analysis to explore the magnitude of this effect, the quality of the evidence, and potential moderators. Methods: A systematic search was conducted to identify studies reporting a comparison between individuals with DCD/probable DCD and typically developing (TD) individuals on measures of internalising symptoms. A pooled effect size (Hedges g) was calculated using random effects meta-analysis. Study quality, publication bias and potential moderators of the effect were explored. Results: Twenty studies, including a total of 23 subsamples, met the inclusion criteria, of which 22 subsamples were included in the meta-analysis (DCD: n=1123; TD: n=7346). A significant, moderate effect of DCD on internalising symptoms was found (g=0.61). This effect remained robust after accounting for publication bias and excluding lower quality studies. The effect was significantly larger in studies utilizing a cross-sectional design (vs. longitudinal), convenience sampling (vs. population screening) and a majority male sample. Conclusions: The findings demonstrate that individuals with DCD experience greater levels of internalising symptoms than their peers. This highlights the importance of routine screening for emotional difficulties in DCD, raising awareness of the condition in mental health services, and developing psychosocial interventions that extend beyond a focus on motor impairments. However, there is a need for higher quality, longitudinal studies to better understand the causal relationship between DCD and internalising symptoms.</p

Analysis of racial/ethnic representation in select basic and applied cancer research studies

Over the past decades, consistent studies have shown that race/ethnicity have a great impact on cancer incidence, survival, drug response, molecular pathways and epigenetics. Despite the influence of race/ethnicity in cancer outcomes and its impact in health care quality, a comprehensive understanding of racial/ethnic inclusion in oncological research has never been addressed. We therefore explored the racial/ethnic composition of samples/individuals included in fundamental (patient-derived oncological models, biobanks and genomics) and applied cancer research studies (clinical trials). Regarding patient-derived oncological models (n = 794), 48.3% have no records on their donor's race/ethnicity, the rest were isolated from White (37.5%), Asian (10%), African American (3.8%) and Hispanic (0.4%) donors. Biobanks (n = 8,293) hold specimens from unknown (24.56%), White (59.03%), African American (11.05%), Asian (4.12%) and other individuals (1.24%). Genomic projects (n = 6,765,447) include samples from unknown (0.6%), White (91.1%), Asian (5.6%), African American (1.7%), Hispanic (0.5%) and other populations (0.5%). Concerning clinical trials (n = 89,212), no racial/ethnic registries were found in 66.95% of participants, and records were mainly obtained from Whites (25.94%), Asians (4.97%), African Americans (1.08%), Hispanics (0.16%) and other minorities (0.9%). Thus, two tendencies were observed across oncological studies: lack of racial/ethnic information and overrepresentation of Caucasian/White samples/individuals. These results clearly indicate a need to diversify oncological studies to other populations along with novel strategies to enhanced race/ethnicity data recording and reporting

Central Neuropeptide Y Modulates Binge-Like Ethanol Drinking in C57BL/6J Mice via Y1 and Y2 Receptors

Frequent binge drinking has been linked to heart disease, high blood pressure, type 2 diabetes, and the development of ethanol dependence. Thus, identifying pharmaceutical targets to treat binge drinking is of paramount importance. Here we employed a mouse model of binge-like ethanol drinking to study the role of neuropeptide Y (NPY). To this end, the present set of studies utilized pharmacological manipulation of NPY signaling, immunoreactivity (IR) mapping of NPY and NPY receptors, and electrophysiological recordings from slice preparations of the amygdala. The results indicated that central infusion of NPY, a NPY Y1 receptor (Y1R) agonist, and a Y2R antagonist significantly blunted binge-like ethanol drinking in C57BL/6J mice (that achieved blood ethanol levels >80 mg/dl in control conditions). Binge-like ethanol drinking reduced NPY and Y1R IR in the central nucleus of the amygdala (CeA), and 24 h of ethanol abstinence after a history of binge-like drinking promoted increases of Y1R and Y2R IR. Electrophysiological recordings of slice preparations from the CeA showed that binge-like ethanol drinking augmented the ability of NPY to inhibit GABAergic transmission. Thus, binge-like ethanol drinking in C57BL/6J mice promoted alterations of NPY signaling in the CeA, and administration of exogenous NPY compounds protected against binge-like drinking. The current data suggest that Y1R agonists and Y2R antagonists may be useful for curbing and/or preventing binge drinking, protecting vulnerable individuals from progressing to the point of ethanol dependence