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Objectives: Evidence on the link between long-term ambient particulate matter (PM) exposures and childhood sleep disorders were scarce. We examined the associations between long-term exposures to PM2.5 and PM1 (PM with an aerodynamic equivalent diameter

Chlorinated polyfluorinated ether sulfonate, commercially known as F-53B, has been associated with adverse birth outcomes. However, the reproductive toxicology of F-53B on the placenta remains poorly understood. To address this gap, we examined the impact of F-53B on placental injury and its underlying molecular mechanisms in vivo. Pregnant C57BL/6 J female mice were randomly allocated to three groups: the control group, F-53B 0.8 µg/kg/day group, and F-53B 8 µg/kg/day group. After F-53B exposure through free drinking water from gestational day (GD) 0.5–14.5, the F-53B 8 µg/kg/day group exhibited significant increases in placental weights and distinctive histopathological alterations, including inflammatory cell infiltration, heightened syncytiotrophoblast knots, and a loosened trophoblastic basement membrane. Within the F-53B 8 µg/kg/day group, placental tissue exhibited increased apoptosis, as indicated by increased caspase3 activation. Furthermore, F-53B potentially induced the NF-κB signaling pathway activation through IκB-α phosphorylation. Subsequently, this activation upregulated the expression of inflammatory cytokines and components of the NLRP3 inflammasome, including activated caspase1, IL-1β, IL-18, and cleaved gasdermin D (GSDMD), ultimately leading to pyroptosis in the mouse placenta. Our findings reveal a pronounced inflammatory injury in the placenta due to F-53B exposure, suggesting potential reproductive toxicity at concentrations relevant to the human population. Further toxicological and epidemiological investigations are warranted to conclusively assess the reproductive health risks posed by F-53B.

Abstract Objective To investigate the relationship between infant feeding practices and autism spectrum disorder (ASD) among children aged 2–5 years in the United States (US). Methods Data from the 2016–2020 National Survey of Children’s Health, a nationally representative cross-sectional survey, were utilized for this study. Questionnaires were administered to parents of children aged 2–5 years to gather information on ASD diagnosis, infant feeding practices, and demographic factors (e.g., child sex, ethnic group, and maternal age at birth). Logistic regression with sample weights was employed to assess the association between infant feeding practices and ASD, while controlling for demographic variables. Polynomial regression models were used to examine trends in exclusive breastfeeding and ever breastfeeding rates among children with and without ASD. Results A total of 35,050 children aged 2–5 years were analyzed, including 616 diagnosed with ASD, after excluding participants with missing information on breastfeeding and ASD diagnosis. Of these children with ASD, 76.6% (n = 472) had a breastfeeding history, with 66.6% (n = 410) engaged in partial breastfeeding and 10.1% (n = 62) exclusively breastfed. Adjusted odds ratios for each additional month of breastfeeding compared to never being breastfed were 0.99 (95% CI, 0.97–1.01). The adjusted odds ratios for breastfeeding durations of > 0–6 months, > 6–12 months, > 12–24 months, and > 24 months were 0.84 (95% CI, 0.51–1.36), 0.76 (95% CI, 0.42–1.35), 0.79 (95% CI, 0.43–1.45), and 0.66 (95% CI, 0.32–1.35), respectively. Compared to children who were never breastfed, the adjusted odds ratio for children who were ever breastfed was 0.79 (95% CI, 0.50–1.25). Among children with ASD, the proportion of ever breastfeeding declined from 82.0% in 2017 to 64.3% in 2020, while exclusive breastfeeding decreased from 12.0% in 2016 to 5.9% in 2020. Conclusions and relevance Although no significant association was found between infant feeding practices and ASD among US children aged 2–5 years, the rates of breastfeeding, particularly exclusive breastfeeding, were suboptimal among children with ASD. This highlights the need for specific policies and practices to promote and support breastfeeding among parents of children with ASD or those at high risk of having a child with ASD.

Background: Adopting a healthy lifestyle during childhood could improve physical and mental health outcomes in adulthood and reduce relevant disease burdens. However, the lifestyles of children with mental, behavioral, and developmental disorders (MBDDs) remains under-described within the literature of public health field. This study aimed to examine adherence to 24-hour movement guidelines among children with MBDDs compared to population norms and whether these differences are affected by demographic characteristics. Methods: Data were from the 2016–2020 National Survey of Children's Health—A national, population-based, cross-sectional study. We used the data of 119,406 children aged 6–17 years, which included 38,571 participants with at least 1 MBDD and 80,835 without. Adherence to the 24-hour movement guidelines was measured using parent-reported physical activity, screen time, and sleep duration. Results: Among children with MBDDs, 20.3%, 37.0%, 60.7%, and 77.3% met the physical activity, screen time, sleep, and at least 1 of the 24-hour movement guidelines. These rates were lower than those in children without MBDDs (22.8%, 46.2%, 66.7%, and 83.4%, respectively; all p < 0.001). Children with MBDDs were less likely to meet these guidelines (odds ratio (OR) = 1.21, 95% confidence interval (95%CI): 1.13–1.30; OR = 1.37, 95%CI: 1.29–1.45; OR = 1.29, 95%CI: 1.21–1.37; OR = 1.45, 95%CI: 1.35–1.56) than children without MBDDs. Children with emotional disorders had the highest odds of not meeting these guidelines (OR = 1.43, 95%CI: 1.29–1.57; OR = 1.48, 95%CI: 1.37–1.60; OR = 1.49, 95%CI: 1.39–1.61; OR = 1.72, 95%CI: 1.57–1.88) in comparison to children with other MBDDs. Among children aged 12–17 years, the difference in proportion of meeting physical activity and screen time guidelines for children with vs. children without MBDD was larger than that among children aged 6–11 years. Furthermore, the above difference of meeting physical activity guidelines in ethnic minority children was smaller than that in white children. Conclusion: Children with MBDDs were less likely to meet individual or combined 24-hour movement guidelines than children without MBDDs. In educational and clinical settings, the primary focus should be on increasing physical activity and limiting screen time in children aged 12–17 years who have MBDDs; and specifically for white children who have MBDDs, increasing physical activity may help.

Background: Previous studies have shown that F-53B exposure may be neurotoxic to animals, but there is a lack of epidemiological evidence, and its mechanism needs further investigation. Methods: Serum F-53B concentrations and Wisconsin Card Sorting Test (WCST) were evaluated in 314 growing children from Guangzhou, China, and the association between them were analyzed. To study the developmental neurotoxicity of F-53B, experiments on sucking mice exposed via placental transfer and breast milk was performed. Maternal mice were orally exposed to 4, 40, and 400 μg/L of F-53B from postnatal day 0 (GD0) to postnatal day 21 (PND 21). Several genes and proteins related to neurodevelopment, dopamine anabolism, and synaptic plasticity were examined by qPCR and western blot, respectively, while dopamine contents were detected by ELISA kit in weaning mice. Results: The result showed that F-53B was positively associated with poor WCST performance. For example, with an interquartile range increase in F-53B, the change with 95 % confidence interval (CI) of correct response (CR), and non-perseverative errors (NPE) was −2.47 (95 % CI: −3.89, −1.05, P = 0.001), 2.78 (95 % CI: 0.79, 4.76, P = 0.007), respectively. Compared with the control group, the highest exposure group of weaning mice had a longer escape latency (35.24 s vs. 51.18 s, P = 0.034) and a lesser distance movement (34.81 % vs. 21.02 %, P

Background: Health risk assessment based on epidemiological data for perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are evidenced. Whereas information about health-based guidance values (HBGVs) and health risk for Chinese population related to PFOS and PFOA is scarce. Objectives: To provide candidate HBGVs for PFOS and PFOA based on Chinese epidemiological data and assess the health risk related to excessive exposure. Methods: We reviewed scientific literature and collected available original data from epidemiological studies conducted in China. Critical endpoints and data were selected and used in benchmark dose (BMD) analysis to obtain lower confidence limits of BMD (BMDLs) of PFOS and PFOA. Physiologically based pharmacokinetic (PBPK) models were applied to calculate the point of departure (PODs) for PFOS and PFOA, which led to the determination of the HBGVs for the said chemicals. Margin of exposure (MOE) method was used to evaluate the health risk of population based on exposure data among Chinese and HBGVs. Results: Alanine aminotransferase (ALT), total cholesterol (TC) and birth weight (BW) were selected as critical endpoints. Epidemiological data from 4,224 adults, 2,153 paired mother-newborn, 2,518 newborns, 439 pregnant women and 733 children in China were included in this study. BMDLs and PODs for PFOS are varied while BMDLs for PFOA were similar. PODs for PFOS (1.56 ng/kg/day) and PFOA (1.52 ng/kg/day) based on BW using National Birth Cohort Study were selected as HBGVs. Most MOEs for PFOS and PFOA among Chinese population were larger than 1 and smaller than 100, indicating moderate concern. Around 16% MOEs for PFOS were smaller than 1, implying high concern. Conclusion: The HBGVs for PFOS and PFOA were 1.56 ng/kg/day and 1.52 ng/kg/day, respectively. Health risk of Chinese population related to PFOS and PFOA exposure should be concerned and more studies should be conducted to evaluate the risk of the chemicals.

Abstract Background Previous studies have revealed that current secondhand smoke exposure showed highly suggestive evidence for increased risk of simultaneous sleep problems in children. Data on the associations between early-life exposure to SHS with subsequent sleep problems in children were scarce. We aimed to evaluate the associations of early-life SHS exposure with sleep problems in children. Methods In this cross-sectional study, children were recruited from elementary and middle schools in Liaoning Province, China between April 2012 and January 2013. We assessed early-life SHS exposure (pregnancy and the first 2 years of life) via questionnaires. Sleep problems and different types of sleep-related symptoms were measured based on the validated tool of the Sleep Disturbance Scale for Children (SDSC). Generalized linear mixed models were applied to estimate the associations of early-life SHS exposure with sleep problems. Results We included a total of 45,562 children (22,657 [49.7%] males; mean [SD] age, 11.0 [2.6] years) and 6167 of them (13.5%) were exposed to early-life SHS during both pregnancy and the first 2 years of life. Compared with unexposed counterparts, children exposed to early-life SHS had higher total T-scores of SDSC (β = 4.32; 95%CI: 4.06, 4.58) and higher odds of increased sleep problems (OR = 2.14; 95%CI: 1.89, 2.42). When considering different sleep-related symptoms, the associations between early-life SHS exposure and symptom of sleep-wake transition disorders (i.e., bruxism) were the strongest in all analyses. Conclusions Early-life SHS exposure was associated with higher odds of global sleep problems and different sleep-related symptoms in children aged 6–18 years. Our findings highlight the importance to strengthen efforts to support the critical importance of maintaining a smoke-free environment especially in early life.

Epidemiological and toxicological evidence show that PM1 is a key driver of PM2.5. However, the particle sizes that play the major damaging role in PM1 is unclear. Our aims were to (1) explore the concentration and chemical composition of ultrafine particles in PM1; (2) evaluate and compare the differences in toxicity of PM1-0.2 and PM0.2 to different airway cell models. We collected PM1-0.2 and PM0.2 in Guangzhou in December 2017, monitored and detected their concentrations, size, and components. A549, THP-1 mono-cultures and A549/THP-1 co-cultured cells were exposed to PM1-0.2 and PM0.2, and evaluated for toxicological responses. PM0.2 contributed to15% PM1 mass and 87.67% to particle number (PN). Most of PM0.2 was PM0.1 (exceed 75%). Structure of particles in PM0.2 were mostly spherical, whereas in PM1-0.2 they were more diverse. Within the same mass unit, PM0.2 contained more chemical components than PM1-0.2; within the same volume, a higher mass of components was found in PM1-0.2. IL-6 and IL-8 were secreted by co-cultured cells in higher manner compared to mono cell cultures. PM0.2-induced higher toxicological responses compared to PM1-0.2. Our findings suggest that high PN concentration and toxicity of ultrafine or PM1 cannot be ignored. Mono-cell culture may underestimate the true PM toxicity.

Background: The associations between per- and polyfluoroalkyl substances (PFAS) and obesity in adolescent remained unclear when considering imaging based methods such as dual-energy X-ray absorptiometry (DXA) scanning. Methods: The 2011-2018 National Health and Nutrition Examination Survey (NHANES) was used in this study. There were four highly detected PFAS including perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA). We calculated total mass, fat mass and fat-free mass (i.e., lean mass including bone mineral content) indexes (mass/height2) of total body and three regions [head, trunk and subtotal (i.e., total minus head)]. We assessed the associations using weighted multivariable linear regression and weighted quantile sum (WQS) regression. Results: A total of 1067 participants aged 12-18 years were included in this study. When adjusting for potential covariates, PFHxS exposure was negatively associated with total fat mass index while positively associated with total fat-free mass index [β=-0.16, 95% confidence interval (CI): -0.27 to -0.04; β=0.16, 95%CI: 0.05 to 0.28]. When entering the PFAS mixture in the WQS model, we found similar associations of WQS index with total fat or fat-free mass index (β=-0.04, 95%CI: -0.08 to -0.00; β=0.04, 95%CI: 0.00 to 0.08). Within the PFAS mixture, PFOA exposure made major contributions to the overall effect (56.6% and 44.1% for total fat and fat-free mass index). We did not find any significant association with regard to PFAS exposure and total mass index. Conclusions: Among US adolescents, higher PFHxS exposure was associated with lower body fat mass and higher fat-free mass in single PFAS models. We observed similar associations of the PFAS mixture with fat and fat-free mass, and PFOA exposure made major contributions to the overall effect. Overall, PFAS exposure might disturb energy balance and body composition in adolescents, and more studies are needed to confirm our findings.

Background:Previous research has suggested that children with autism spectrum disorder (ASD) display fewer prosocial behaviors, and the role of empathy or Theory of Mind (ToM) in prosocial behaviors of autistic children remains unclear.MethodsData were obtained from an ongoing longitudinal study in Guangzhou, China. A total of 96 autistic children and 167 typically developing (TD) children were enrolled. Prosocial behaviors were assessed using a subscale of the Strength and Difficulties Questionnaire and Dictator Game (DG) paradigm with stickers as incentives. Empathic traits and ToM ability were measured using the children's Empathy Quotient and the Chinese version of ToM toolkit. Generalized linear models were used to assess the differences of prosocial behaviors and empathic traits, ToM ability between the two groups and the associations between empathic traits, ToM ability and prosocial behaviors in autistic children.ResultsCompared with TD children, autistic children exhibited worse ToM ability and performed less pro-socially in the DG paradigm, while there were no differences regarding empathic traits. In autistic children, empathic traits especially affective empathy, were positively associated with parent-reported prosocial behaviors [β = 0.17, 95% confidence interval (CI): 0.07–0.27; β = 0.47, 95%CI: 0.33–0.60]. ToM ability was associated with DG paradigm (β = 1.03, 95%CI: 0.16–1.89).ConclusionAutistic children showed less pro-sociality and ToM ability than TD children. In autistic children, empathic trait was associated with parent-reported prosocial behaviors while their ToM ability was associated with prosocial behaviors in experimental condition. Our findings indicated that better ToM ability and empathic trait might promote prosocial behaviors in autistic children.

Abstract Background Childhood obesity is a serious public health concern. School-based interventions hold great promise to combat the rising trend of childhood obesity. This systematic review aimed to assess the overall effects of school-based obesity prevention interventions, and to investigate characteristics of intervention components that are potentially effective for preventing childhood obesity. Methods We systematically searched MEDLINE, CENTRAL and Embase databases to identify randomized- or cluster randomized- controlled trials of school-based obesity interventions published between 1990 and 2019. We conducted meta-analyses and subgroup analyses to determine the overall effects of obesity prevention programs and effect differences by various characteristics of intervention components on body mass index (BMI) or BMI Z-score of children. Results This systematic review included a total of 50 trials (reported by 56 publications). Significant differences were found between groups on BMI (− 0.14 kg/m2 (95% confidence interval: − 0.21, − 0.06)) and BMI Z-score (− 0.05 (− 0.10, − 0.01)) for single-component interventions; significant differences were also found between groups on BMI (− 0.32 (− 0.54, − 0.09) kg/m2) and BMI Z-score (− 0.07 (− 0.14, − 0.001)) for multi-component interventions. Subgroup analyses consistently demonstrated that effects of single-component (physical activity) interventions including curricular sessions (− 0.30 (− 0.51, − 0.10) kg/m2 in BMI) were stronger than those without curricular sessions (− 0.04 (− 0.17, 0.09) kg/m2 in BMI); effects of single-component (physical activity) interventions were also strengthened if physical activity sessions emphasized participants’ enjoyment (− 0.19 (− 0.33, − 0.05) kg/m2 in BMI for those emphasizing participants’ enjoyment; − 0.004 (− 0.10, 0.09) kg/m2 in BMI for those not emphasizing participants’ enjoyment). The current body of evidence did not find specific characteristics of intervention components that were consistently associated with improved efficacy for multi-component interventions (P > 0.05). Conclusions School-based interventions are generally effective in reducing excessive weight gain of children. Our findings contribute to increased understandings of potentially effective intervention characteristics for single-component (physical activity) interventions. The impact of combined components on effectiveness of multi-component interventions should be the topic of further research. More high-quality studies are also needed to confirm findings of this review.

Numerous studies have demonstrated that exposure to ambient ozone (O3) could have adverse effects on children’s respiratory health. However, previous studies mainly focused on asthma and wheezing. Evidence for allergic rhinitis and bronchitic symptoms (e.g., persistent cough and phlegm) associated with O3 is limited, and results from existing studies are inconsistent. This study included a total of 59,754 children from the seven northeastern cities study (SNEC), who were aged 2 to 17 years and from 94 kindergarten, elementary and middle schools. Information on doctor-diagnosed allergic rhinitis (AR), persistent cough, and persistent phlegm was collected during 2012–2013 using a standardized questionnaire developed by the American Thoracic Society (ATS). Information for potential confounders was also collected via questionnaire. Individuals’ exposure to ambient ozone (O3) during the four years before the investigation was estimated using a satellite-based random forest model. A higher level of O3 was significantly associated with increased risk of AR and bronchitic symptoms. After controlling for potential confounders, the OR (95% CI) were 1.13 (1.07–1.18), 1.10 (1.06–1.16), and 1.12 (1.05–1.20) for AR, persistent cough, and persistent phlegm, respectively, associated with each interquartile range (IQR) rise in O3 concentration. Interaction analyses showed stronger adverse effects of O3 on AR in children aged 7–17 years than those aged 2–6 years, while the adverse association of O3 with cough was more prominent in females and children aged 7–12 years than in males and children aged 2–6 and 13–17 years. This study showed that long-term exposure to ambient O3 was significantly associated with higher risk of AR and bronchitic symptoms in children, and the association varies across age and gender. Our findings contribute additional evidence for the importance of controlling O3 pollution and protecting children from O3 exposure.

The toxicity of ultrafine particles (UFPs) on blood pressure (BP) has not been well studied. We aimed to evaluate the associations of long-term UFP exposure with different components of BP and the risk of prehypertension/hypertension. We included a total of 24 845 Chinese adults (18–74 years old) in a cross-sectional survey (Liaoning province, China). The 4 year (2006–2009) average concentrations of UFP was estimated using a chemical transport model. We measured systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and pulse pressure (PP), prehypertension and hypertension. We used a generalized linear mixed model to examine the associations while controlling for important individual covariates. One unit (1 μ g m ^−3 ) increase in UFP was associated with an increase in SBP of 1.52 mm Hg [95% confidence interval (CI): 0.48–2.55], DBP of 0.55 mm Hg (95% CI: 0.01–1.08) in DBP, MAP of 0.92 mm Hg (95% CI: 0.23–1.61) and PP of 0.62 mm Hg (95% CI: 0.05–1.20). The UFP-BP associations were stronger in women than in men. One unit increase in UFP was associated with an increased risk of hypertension and prehypertension (OR = 1.23, 95% CI: 1.09–1.38; OR = 1.12, 95% CI: 1.04–1.21) compared to normotension group, and these associations were stronger in overweight/obese participants. Our study showed that long-term exposure to UFP was associated with elevated BP and higher odds of hypertension. These findings suggest that strategies to monitor and reduce UFPs, which are not a regulated pollutant, could have beneficial cardiovascular effects.

Nanotechnology is one of the scientific advances in technology. Nanoparticles (NPs) are small materials ranging from 1 to 100 nm. When the shape of the supplied nanoparticles changes, the physiological response of the cells can be very different. Several characteristics of NPs such as the composition, surface chemistry, surface charge, and shape are also important parameters affecting the toxicity of nanomaterials. This review covered specific topics that address the effects of NPs on nanomedicine. Furthermore, mechanisms of different types of nanomaterial-induced cytotoxicities were described. The distributions of different NPs in organs and their adverse effects were also emphasized. This review provides insight into the scientific community interested in nano(bio)technology, nanomedicine, and nanotoxicology. The content may also be of interest to a broad range of scientists.

The property of drug-resistance may attenuate clinical therapy in cancer cells, such as chemoresistance to gefitinib in colon cancer cells. In previous studies, overexpression of PD-L1 causes proliferation and metastasis in cancer cells; therefore, the PD-L1 pathway allows tumor cells to exert an adaptive resistance mechanism in vivo. Nano-diamino-tetrac (NDAT) has been shown to enhance the anti-proliferative effect induced by first-line chemotherapy in various types of cancer, including colorectal cancer (CRC). In this work, we attempted to explore whether NDAT could enhance the anti-proliferative effect of gefitinib in CRC and clarified the mechanism of their interaction. The MTT assay was utilized to detect a reduction in cell proliferation in four primary culture tumor cells treated with gefitinib or NDAT. The gene expression of PD-L1 and other tumor growth-related molecules were quantified by quantitative polymerase chain reaction (qPCR). Furthermore, the identification of PI3K and PD-L1 in treated CRC cells were detected by western blotting analysis. PD-L1 presentation in HCT116 xenograft tumors was characterized by specialized immunohistochemistry (IHC) and the hematoxylin and eosin stain (H&E stain). The correlations between the change in PD-L1 expression and tumorigenic characteristics were also analyzed. (3) The PD-L1 was highly expressed in Colo_160224 rather than in the other three primary CRC cells and HCT-116 cells. Moreover, the PD-L1 expression was decreased by gefitinib (1 µM and 10 µM) in two cells (Colo_150624 and 160426), but 10 µM gefitinib stimulated PD-L1 expression in gefitinib-resistant primary CRC Colo_160224 cells. Inactivated PI3K reduced PD-L1 expression and proliferation in CRC Colo_160224 cells. Gefitinib didn't inhibit PD-L1 expression and PI3K activation in gefitinib-resistant Colo_160224 cells. However, NDAT inhibited PI3K activation as well as PD-L1 accumulation in gefitinib-resistant Colo_160224 cells. The combined treatment of NDAT and gefitinib inhibited pPI3K and PD-L1 expression and cell proliferation. Additionally, NDAT reduced PD-L1 accumulation and tumor growth in the HCT116 (K-RAS mutant) xenograft experiment. (4) Gefitinib might suppress PD-L1 expression but did not inhibit proliferation through PI3K in gefitinib-resistant primary CRC cells. However, NDAT not only down-regulated PD-L1 expression via blocking PI3K activation but also inhibited cell proliferation in gefitinib-resistant CRCs.

Background: Although the indoor environment has been proposed to be associated with childhood sleep health, to our knowledge no study has investigated the association between home renovation and childhood sleep problems. Methods: The study included 186,470 children aged 6-18 years from the National Chinese Children Health Study (2012-2018). We measured childhood sleeping problems via the Chinese version of the Sleep Disturbance Scale for Children (C-SDSC). Information on home renovation exposure within the recent 2 years was collected via parent report. We estimated associations between home renovation and various sleeping problems, defined using both continuous and categorized (binary) C-SDSC t-scores, using generalized mixed models. We fitted models with city as a random effect variable, and other covariates as fixed effects. Results: Out of the overall participants, 89,732 (48%) were exposed to recent home renovations. Compared to the unexposed group, children exposed to home renovations had higher odds of total sleep disorder (odd ratios [OR] = 1.3; 95% confidence interval [CI] = 1.2, 1.4). Associations varied when we considered different types of home renovation materials. Children exposed to multiple types of home renovation had higher odds of sleeping problems. We observed similar findings when considering continuous C-SDSC t-scores. Additionally, sex and age of children modified the associations of home renovation exposure with some of the sleeping problem subtypes. Conclusions: We found that home renovation was associated with higher odds of having sleeping problems and that they varied when considering the type of renovation, cumulative exposure, sex, and age differences. [ABSTRACT FROM AUTHOR]

Social hierarchy greatly influences behavior and health. Both human and animal studies have signaled the medial prefrontal cortex (mPFC) as specifically related to social hierarchy. Dopamine D1 receptors (D1Rs) and D2 receptors (D2Rs) are abundantly expressed in the mPFC, modulating its functions. However, it is unclear how DR-expressing neurons in the mPFC regulate social hierarchy. Here, using a confrontation tube test, we found that most adult C57BL/6J male mice could establish a linear social rank after 1 week of cohabitation. Lower rank individuals showed social anxiety together with decreased serum testosterone levels. D2R expression was significantly downregulated in the dorsal part of mPFC (dmPFC) in lower rank individuals, whereas D1R expression showed no significant difference among the rank groups in the whole mPFC. Virus knockdown of D2Rs in the dmPFC led to mice being particularly prone to lose the contests in the confrontation tube test. Finally, simultaneous D2R activation in the subordinates and D2R inhibition in the dominants in a pair switched their dominant–subordinate relationship. The above results indicate that D2Rs in the dmPFC play an important role in social dominance. Our findings provide novel insights into the divergent functions of prefrontal D1Rs and D2Rs in social dominance, which may contribute to ameliorating social dysfunctions along with abnormal social hierarchy. [ABSTRACT FROM AUTHOR]