Perineuronal nets (PNNs) are extracellular matrix structures that predominantly surround PV+ inhibitory interneurons. We have previously shown that PNNs in the medial prefrontal cortex (mPFC) are essential in the extinction and reconsolidation of methamphetamine (MA)-induced conditioned place preference (CPP). However, whether PNNs and PV+ interneurons in the mPFC are also involved in the acquisition phase of MA-induced CPP remains unclear. In this study, we investigated neuronal activity in the prelimbic cortex (PL) of the mPFC in relation to MA-induced CPP. The expression of c-Fos and ΔFosB dramatically increased following MA-induced CPP expression. In vivo calcium imaging demonstrated that both Ca2+ activity and event frequency, as well as the area under the curve (AUC) for calcium imaging signals in the PL, were elevated during MA-induced CPP conditioning and expression. The quantity of PNNs and PV+ neurons, along with co-labeled PNNs+/PV+ cells, dramatically rose following the CPP test and showed a positive correlation with MA preference. The elimination of PNNs from the PL by chondroitinase ABC (ChABC) diminished the expression of MA-induced CPP and lowered the quantity of PV+ and c-Fos+ neurons. Moreover, the targeted suppression of PV+ interneuron activity via an hM4D(Gi) DREADD strategy in PV-Cre animals throughout the conditioning stages markedly disrupted MA-induced CPP development and diminished Ca2+ activity in the PL. These findings indicate that both PNNs and PV+ interneurons in the PL are essential in the acquisition phase of MA-induced CPP and may serve as potential targets in treating MA addiction.

Background Cardiac hypertrophy plays an important role in organ damage caused by hypertension and may progress into heart failure. This study investigated the function and underlying mechanisms of phosphofurin acidic cluster sorting protein 2 (PACS2) in relation to cardiac hypertrophy. Materials and methods To create both in vitro and in vivo models, Ang-II stimulation and transverse aortic constriction (TAC) were employed. The cross-sectional area of cardiomyocytes was measured through immunofluorescence, while gene and protein expression levels were analyzed using RT-qPCR and Western blot. Myocardial damage was evaluated by H&E staining, and cardiac function was determined assessed through echocardiography. Results Ang-II treatment triggered hypertrophic changes, increased expression levels of ANP, BNP, Myh7, Acta1 and PACS2, and activated oxidative stress along with ferroptosis in cardiomyocytes. Silencing of PACS2 led to a decrease in hypertrophy, oxidative stress, and ferroptosis, while promoting the nuclear translocation of Nrf2 and activating the Nrf2/HO-1 signaling pathway both in Ang-II-treated cardiomyocytes and in TAC rats. Ang-II treatment caused a decline in SIRT1 expression level, which was restored upon PACS2 inhibition. The protective benefits of PACS2 knockdown were partially negated by the inhibition of SIRT1. In animal models, PACS2 silencing alleviated myocardial damage and hypertrophy in TAC rats, which was accompanied by increased activation of Nrf2/HO-1 and an inhibition in ferroptosis, both of which were rescued by SIRT1 inhibition. Mechanistically, PACS2 regulated SIRT1 expression through its interaction with the transcription factor HIC1. Conclusion Silencing of PACS2 attenuates cardiac hypertrophy caused by Ang-II in vitro and TAC in vivo by repressing oxidative stress and ferroptosis, which is facilitated by the activation of the Nrf2/HO-1 signaling pathway through the enhancement of SIRT1 expression via its interaction with HIC1.

Objectives: Clinically feasible simple methods for prognostic assessment of cardioinhibitory vasovagal syncope (VVS) are rare. This study investigated the predictive utility of head-up tile test (HUTT) data among cardioinhibitory VVS children with non-pharmacological therapy. Methods: A retrospective analysis was conducted on the clinical data of 403 children with VVS who had cardioinhibitory responses induced by HUTT. The children were aged 4-18 years old, including 178 males and 225 females. After the non-pharmacological interventions and follow-up, they were divided into the good prognosis group (233 cases) and the poor prognosis group (170 cases). Results: (1) Comparison between groups: Compared with the good prognosis group, the baseline heart rate (HR0) in the poor prognosis group was lower, and the proportion of sublingual nitroglycerin-provoked HUTT (SNHUT) was higher (p < 0.05). (2) Univariate analysis: Univariate analysis showed that HR0 was a protective factor on the prognosis of VVS, while SNHUT was a risk factor for the prognosis of VVS. (3) Multivariate analysis: HR0 was an independent protective factor on the prognosis of VVS. That is, for every 1 bpm increase in HR0, the risk of poor prognosis of VVS decreased by 3%. SNHUT was an independent risk factor for the prognosis of VVS, and the risk of poor prognosis of VVS increased by 3.34 times compared with basic HUTT (BHUT). (4) Evaluation of diagnostic tests: The combination of HR0 and HUTT mode had a good prognostic prediction effect for VVS (AUC = 0.71, p < 0.001). Conclusions: The combination of HR0 and HUTT mode demonstrates robust prognostic predictive value for non-pharmacological interventions in pediatric patients with VVS exhibiting cardioinhibitory responses during HUTT.

INTRODUCTION:The ryanodine receptor 2 gene mutation associated with catecholaminergic polymorphic ventricular tachycardia is one of the aetiologies of cardiac syncope and has the risk of sudden cardiac death. This study reported two novel ryanodine receptor 2 gene variants. CASE DESCRIPTION:We described two 9-year-old girls with recurrent syncope during exercise or stress presenting two novel ryanodine receptor 2 gene variants (c.6938T>G/p. Val2313Gly and c.12263A>C/p. His4088Pro) associated with catecholaminergic polymorphic ventricular tachycardia through a comprehensive review of medical history, examination findings and genetic testing. Propranolol was used for treatment, and the two patients didn't experience episodes of syncope during follow-up for 6 months. Besides, literature associated with catecholaminergic polymorphic ventricular tachycardia and ryanodine receptor 2 mutations was reviewed. CONCLUSIONS:Recurrent syncope during exertion or stress should be focused on catecholaminergic polymorphic ventricular tachycardia caused by ryanodine receptor 2 gene mutations. The genetic testing is a crucial tool in confirming the mutation of catecholaminergic polymorphic ventricular tachycardia. Early recognition of this disease, timely diagnosis of ryanodine receptor 2 gene mutations, and administration of appropriate pharmacological agents or ICD implantation are critical to ensure favourable clinical outcomes.

Objective: To investigate the changes in T-wave amplitude and Tp-Te interval on supine and standing electrocardiograms (ECGs) in pediatric postural orthostatic tachycardia syndrome (POTS), and to explore their predictive value for the therapeutic effect of metoprolol. Methods: A total of 59 children diagnosed with POTS who presented with syncope or pre-syncopal symptoms were enrolled as the POTS group, and 52 healthy children served as the control group. Supine and standing ECGs were recorded for all subjects, and T-wave amplitude and Tp-Te interval were measured. Children with POTS were followed-up after metoprolol treatment and divided into a therapeutic response group and a non-response group. Results: (1) Comparison of supine vs. standing ECGs: In the POTS group, standing posture (compared with supine posture) was associated with increased heart rate (HR), decreased T-wave amplitude in leads II, III, aVF, V4, V5, and V6, shortened Tp-Te interval in leads I, II, III, aVR, aVF, V1, V3, V4, V5, and V6, and elevated Tp-Te/QT ratio in leads aVL and V5 (all p < 0.05). (2) Comparison with the control group: The POTS group exhibited a greater HR difference (ΔHR), as well as larger differences in T-wave amplitude (ΔT-wave amplitude) between supine and standing positions in leads II, aVR, aVL, aVF, V3, and V5 (all p < 0.05). (3) Follow-up: Compared with the non-response group, the therapeutic response group showed larger ΔT-wave amplitude in leads III, aVF, V2, V3, V4, and V5, larger Tp-Te interval difference (ΔTp-Te interval) in lead V3, and larger Tp-Te/QT ratio difference (ΔTp-Te/QT ratio) in lead V3 (all p < 0.05). (4) Receiver operating characteristic curve: ΔT-wave amplitude in leads III, aVF, V2, V3, V4, and V5, ΔTp-Te interval in lead V3, and ΔTp-Te/QT ratio in lead V3 all had predictive value for the therapeutic effect of metoprolol in pediatric POTS (all p < 0.05). Conclusions: ΔHR and ΔT-wave amplitude in lead V5 between supine and standing positions are independent risk factors for pediatric POTS. A combination of five indicators-ΔT-wave amplitude in leads V2, V3, and V5, ΔTp-Te interval in lead V3, and ΔTp-Te/QT ratio in lead V3 between supine and standing ECGs-exerts a good predictive effect on the therapeutic response of pediatric POTS to metoprolol intervention.

Objective: This study aimed to compare the therapeutic effects of music therapy and white noise on sleep quality and psychological resilience enhancement in night-shift nurses.Methods: A quasi-experimental retrospective analysis was performed on 100 night-shift nurses enrolled in hospital-based health management programs between April 2024 and April 2025. The participants were categorised by program type: the music group (n = 52) received music-based care from April 2024 to September 2024, and the white noise group (n = 48) underwent white noise exposure from October 2024 to April 2025. The following were assessed before the program and at 4-week post-implementation: sleep quality (Pittsburgh Sleep Quality Index [PSQI]), circadian flexibility (Circadian Type Inventory-11 [CTI-11] with Flexibility/Rigidity [FR] and Languidness/Vigorousness [LV] subscales), psychological resilience (10-item Connor-Davidson Resilience Scale [CD-RISC-10]), occupational burnout (Maslach Burnout Inventory-General Survey [MBI-GS]) and emotional labour management (Emotional Labor Scale [ELS]). An independent sample t-test was used to compare the differences between groups, and the effect size of the differences was quantified by Cohen’s d. Results: At 4-week post-implementation, the white noise group demonstrated significantly lower PSQI scores (P < 0.05), CTI-11 LV subscale scores (P < 0.05), CD-RISC-10 scores (P < 0.05) and diminished genuine emotion expression dimension scores on the ELS (P < 0.05) compared with the music group. Conversely, the white noise group had significantly higher CTI-11 FR subscale scores (P < 0.05), MBI-GS scores (P < 0.05) and surface acting plus deep acting dimension scores on the ELS (P < 0.05) compared with the music group. Conclusion: Music therapy and white noise exposure effectively enhance sleep quality, circadian adaptability, psychological resilience, occupational burnout recovery and emotional labour regulation in night-shift nurses. White noise demonstrates greater efficacy for sleep quality and circadian rhythm optimisation. Music therapy provides superior psychological resilience enhancement, burnout reduction and emotional labour management.

BACKGROUND:Malignant vasovagal syncope (VVS) is characterized by cardiac arrest lasting more than 3 seconds during a syncope episode or head-up tilt test (HUTT). We aim to conduct a risk assessment for potential malignant VVS before the HUTT by using economic, simple and convenient demographic data, in order to prevent adverse outcomes for pediatric VVS. PURPOSE:To explore the correlation between demographic factors and pediatric malignant VVS, and verify the value of these factors in early risk assessment for malignant VVS before HUTT, so as to optimize test safety and reduce adverse events. METHODS:We conducted a retrospective analysis of the clinical data of 3,734 children who were initially diagnosed with VVS due to unexplained syncope and presyncope. Finally, 122 children who met the diagnostic criteria for malignant VVS were included in the malignant VVS group, and 661 children who did not meet the criteria during the same period were matched as the control group. By analyzing demographic data and other factors, we attempted to clarify the association between these factors and malignant VVS. RESULTS:Linear relationship: age and body mass index (BMI) have independent protective effects on malignant VVS. For every 1-year increase in age and every 1 kg/m2 increase in BMI, the risk of malignant VVS decreases by 12% and 9%, respectively. Nonlinear relationship: When the age is <12.9 years old, for every additional year of age, the risk of malignant VVS decreases by 20%. For ages 12.9 years and above, the efficacy is not significant. There is no significant nonlinear relationship between BMI and malignant VVS. CONCLUSION:Age and BMI are independent protective factors for pediatric malignant VVS. Before the age of 12.9 years, the incidence of malignant VVS gradually decreases with the increase in age, and thereafter there is no significant impact.

Methamphetamine (MA) addiction is characterized by persistent drug-associated memory and high relapse risk. Perineuronal nets (PNNs), which mainly surround PV interneurons, are specialized extracellular matrix structures involved in synaptic stabilization and memory regulation. Our previous studies have shown that PNNs in the medial prefrontal cortex (mPFC) are essential for MA-induced conditioned place preference (CPP) memory, but the role of hippocampal PNNs in MA-associated contextual memory remains unclear. Here, a CPP paradigm was employed in female mice to investigate the role and underlying mechanisms of hippocampal PNNs in MA-induced reward memory. During MA-induced CPP acquisition, the number of c-Fos and PNNs in the hippocampal CA1 was significantly increased. Digestion of PNNs using chondroitinase ABC (ChABC) or knockdown of the key PNNs component Aggrecan in the ventral CA1 (vCA1) but not dorsal CA1 (dCA1) suppressed the acquisition of MA-induced CPP and reduced the immunoreactivity of PV and c-Fos. In addition, chemogenetic inhibition of PV interneurons in the vCA1 of Pvalb-IRES-Cre mice using the hM4D(Gi) DREADD strategy also suppressed CPP acquisition, supporting a critical role for PV interneuron activity in this process. Together, our findings indicate that MA-induced increased PNNs in the vCA1 promote the formation of CPP memory by regulating PV interneuron activity. This study provides new evidence for the region-specific role of hippocampal PNNs in drug-associated memory and suggests that targeting vCA1 PNNs and PV interneurons may represent a potential therapeutic strategy for MA addiction.

Background: Disrupted hippocampal functions and progressive neuronal loss represent significant challenges in the treatment of Alzheimer's disease (AD). How to achieve the improvement of pathological progression and effective neural regeneration to ameliorate the intracerebral dysfunctional environment and cognitive impairment is the goal of the current AD therapy. Methods: We examined the therapeutic potential of clinical-grade human derived dental pulp stem cells (hDPSCs) in cognitive function and neuropathology in AD. Specifically, we investigated the effect of neural crest-specific derived hDPSCs on endogenous neural regeneration and long-term efficacy following a single transplantation in the triple-transgenic mouse model (3xTg-AD). Results: Our research demonstrated that a single administration of clinical-grade hDPSCs yielded dramatic short-term therapeutic benefits (5 weeks) and sustained partial efficacy (6 months) with respect to improving cognitive impairment and delaying typical pathological progression in 3xTg-AD mice. Intriguingly, exogenous hDPSCs were robustly self-differentiated into newborn functional neurons in the hippocampus of 3xTg-AD mice. The foremost evidence is provided that hDPSCs promote endogenic neural regeneration by enhancing the activation of the Wnt/beta-catenin pathway, which may contribute to stabilizing the hippocampal neural network to reverse memory deficits. Conclusion: These findings highlight the multifunctional potential of hDPSCs in AD treatment, which enhances cognition through alleviating neuropathology and providing neural regenerative driving force. Understanding these multiplicity effects is critical to advancing the clinical translation of stem cell-based therapies for AD.

Lipid metabolism disorders represent a significant risk factor for the pathogenesis of Alzheimer’s disease (AD). Apolipoprotein E (APOE) has been regarded as a pivotal regulator of lipid homeostasis in the central nervous system (CNS), with polymorphic alleles identified as genetic risk factors for late-onset AD. Despite advances in APOE research and the development of numerous pharmaceutical approaches targeting distinct APOE isoforms, there remain limited treatment approaches for AD that focus on lipid metabolic homeostasis. Consequently, it is necessary to reevaluate the lipid metabolic process in the CNS. Apolipoprotein A1 (APOA-I), a major component of high-density lipoprotein (HDL), plays a crucial role in reverse cholesterol transport from tissues to the liver to maintain lipid homeostasis. Over the past few decades, numerous studies have suggested a connection between reduced APOA-I levels and a higher risk of AD. APOA-I is synthesized exclusively in the liver and intestines, and there is a lack of conclusive evidence supporting its functional significance within the central nervous system, in contrast to APOE, which is produced locally by glial cells and neurons within the CNS. Moreover, APOA-I’s ability to penetrate the blood-brain barrier (BBB) is still poorly understood, which causes its significance in central lipid metabolism and AD pathophysiology to be mainly disregarded. Recent advancements in tracing methodologies have underscored the essential role of APOA-I in regulating lipid metabolism in the CNS. This review aims to elucidate the physiological functions and metabolic pathways of APOA-I, integrating its associations with AD-related pathologies, risk factors, and potential therapeutic targets. Through this discourse, we aim to provide novel insights into the intricate relationship between AD and APOA-I, paving the way for future research in this field.

To investigate the correlation between prognostic nutritional index (PNI) and vasovagal syncope (VVS) in children, as well as its predictive value. 151 children (68 males, aged 4–18 years) diagnosed with VVS due to unexplained syncope and presyncope in our hospital from January 2022 to December 2023 were the study group, 152 healthy children (72 males, aged 7–14 years) who underwent physical examination in the same hospital during the same period of time were matched as the control group. Serum albumin (SA), serum globulin (SG), albumin/globulin (AGR), and peripheral blood lymphocyte absolute count (Lc) were measured, and PNI was calculated. ①PNI (51.35 vs. 55.28), SA (40.90 g/L vs. 43.05 g/L), AGR (1.65 vs. 1.75), and Lc (2.08 × 109/L vs. 2.49 × 109/L) were decreased in VVS group compared with control group (P < 0.05). ②Predictive analysis of VVS by PNI: The area under receiver operator characteristic curve of PNI prediction of VVS was 0.814, which indicated that PNI had moderate predictive value for VVS diagnosis. When PNI cutoff value was 55.00, the sensitivity, specificity, and Youden index of predicting VVS were 90.73

Drug addiction is characterized by compulsive drug use despite significant negative consequences. N-acetyltransferase 10 (NAT10), a member of the Gcn5-related N-acetyltransferases (GNAT) family, has been associated with depression, anxiety-like behaviors, and cognitive dysfunction. However, its role in addiction remains largely unknown. In the present study, we observed increased expression of NAT10 in the nucleus accumbens (NAc) of mice treated either singly or repeatedly with 2 mg/kg methamphetamine (METH). To assess the role of NAT10 in addiction-related behaviors, we established mouse models of conditioned place preference (CPP) and hyperlocomotion. Using intraperitoneal administration of 0.1 mg/kg SCH23390, a dopamine D1 receptor (D1R) antagonist, we found that D1R antagonism significantly suppressed the METH-induced upregulation of NAT10 in the NAc and inhibited hyperlocomotion. Furthermore, stereotaxic delivery of a short hairpin RNA (shRNA)-based adeno-associated virus (AAV-shNAT10) into the NAc reduced both METH-induced hyperlocomotion and CPP. AAV-shNAT10 also inhibited METH-induced upregulation of PSD95 and preserved dendritic morphology in the NAc. These findings suggest that NAT10 contributes to the development of METH-induced reward-related behaviors by modulating dendritic plasticity in the NAc.

Early life experience modulates resilience to stress in later life. Previous research implicated maternal care as a key mediator of behavioral responses to the adversity in adolescence, but details of molecular mechanisms remain elusive. Here, we show social stress activates transcription factor C/EBPβ in mPFC neurons of adolescent mice, which transcriptionally upregulates Dnm1l and promotes mitochondrial dysfunction, thereby conferring stress susceptibility in adolescent mice. Moreover, different maternal separation differentially regulates adolescent stress susceptibility. Mechanistically, this differential effect depends on maternal behavior-stimulated IGF-1, which inhibits neuronal C/EBPβ through mTORC1-induced C/EBPβ-LIP translation. Furthermore, we identify maternal behavior-stimulated IGF-1 is mainly released from mPFC microglia. Notably, increased maternal care under an environmental enrichment condition or maternal behavior impairment induced by repeated MPOAEsr1+ cells inhibition in dams prevents or promotes stress susceptibility via microglial-to-neuronal IGF-1-C/EBPβ-DRP1 signaling. In this work, these findings have unveiled molecular mechanisms by which maternal behavior promotes stress resilience in adolescents. Early life experience modulates stress resilience in later life. Here the authors show that maternal care triggers microglia-derived IGF-1 levels, which suppresses the neuronal C/EBPβ-DRP1 axis, promoting stress resilience in adolescent mice.

BACKGROUND:Both psychogenic pseudosyncope (PPS) and vasovagal syncope (VVS) in children and adolescents are diseases of transient loss of consciousness. It is difficult to distinguish them clinically. This paper will study the differential diagnostic value of P wave dispersion (Pd) and QT interval dispersion (QTd) between PPS and VVS. METHODS:The 31 children with PPS and 40 children with VVS from July 2014 to November 2023 were enrolled as the study group. Meanwhile, 30 healthy children who underwent a physical examination at the same hospital were matched to the control group. P wave duration and QT interval in the 12-lead electrocardiogram were measured at the baseline. RESULTS:(1) Comparison between groups: ① The Pd, corrected P wave dispersion (Pcd), QTd, and corrected QT interval dispersion (QTcd) in PPS group were significantly higher than those in control group (P < 0.05). The minimum P wave duration (Pmin) and corrected P wave duration (Pcmin) in PPS group were significantly lower than those in control group (P < 0.05). There were no significant differences in maximum P wave duration (Pmax), corrected maximum P-wave duration (Pcmax), maximum QT interval (QTmax), minimum QT interval (QTmin), corrected maximum QT interval (QTcmax), and corrected minimum QT interval (QTcmin) between PPS group and control group (P > 0.05). ② The Pd, Pcd, QTd, and QTcd in VVS group were significantly higher than those in control group (P < 0.05). The Pmin, Pcmin, and QTcmin in VVS group were significantly lower than those in control group (P < 0.05). There were no significant differences in Pmax, Pcmax, QTmax, QTmin, and QTcmax between VVS group and control group (P > 0.05). ③ The Pmax, Pd, QTmax, QTd, and QTcd in PPS group were significantly lower than those in VVS group (P < 0.05). There were no significant differences in Pmin, Pcmax, Pcmin, Pcd, QTmin, QTcmax, and QTcmin between PPS group and VVS group (P > 0.05). (2) ROC curve: Pmax, Pd, QTmax, QTd, and QTcd had a certain differential diagnostic value between PPS and VVS in children and adolescents (P < 0.05). QTd had the largest area under curve (0.735), with a sensitivity of 85.00% and a specificity of 53.30% at the cut off value of ≥ 28.11 ms for VVS diagnosis. CONCLUSIONS:In children and adolescents, electrocardiogram parameters such as Pmax, Pd, QTmax, QTd, and QTcd all possess predictive value in differentiating between PPS and VVS. Among them, QTd has the greatest differential diagnostic value.

Situational syncope refers to syncope that occurs in specific situations and is a special type of neurally mediated syncope. The etiologic composition of situational syncope varies between adults and children. In adults, it is more common during micturition and defecation, whereas in children, it is more frequently seen during flag-raising, micturition, and defecation. The clinical features and underlying mechanisms of various types of situational syncope also differ in terms of age and sex. The treatment of situational syncope mainly includes nonpharmacologic treatment, pharmacologic treatment, and surgical treatment. Adverse events related to situational syncope are rare, and the prognosis is generally good if there are no other systemic diseases. However, in patients with underlying cardiovascular diseases, situational syncope can lead to serious cardiovascular adverse events.

BACKGROUND:Headache and dizziness are common symptoms in children and adolescents, but the causes of headache/dizziness in most pediatric patients are not clearly defined. We intended to investigate the demographic and clinical features of pediatric patients with headache and/or dizziness and responses to head-up tilt test (HUTT). METHODS:The demographic data and medical records of children and adolescents, with a primary complaint of headache and/or dizziness and undergoing HUTT between January 2001 and June 2023, were retrospectively reviewed and analyzed. Children and adolescents with headache and/or dizziness secondary to fever, trauma, or other obvious etiology were excluded. For those with positive responses to HUTT, the symptom score and HUTT responses were collected after treatment at follow-up. RESULTS:Among 2709 patients with unexplained headache and/or dizziness, 1080 (39.87%) cases presented positive responses to HUTT, whereas 1629 (60.13%) cases had negative responses. Among patients with positive responses, 930 (34.33%) cases presented a response of vasovagal syncope, 143 (5.28%) cases of postural orthostatic tachycardia syndrome, and 7 (0.26%) cases of orthostatic hypertension. Multivariate Logistic regression analysis demonstrated that females, older age, and low body mass index percentile increased the risk of being positive responses. At follow-up, HUTT results of 236 patients were collected, among which 131 (55.51%) cases turned negative HUTT responses and had headache/dizziness symptoms improved after treatment targeted autonomic dysfunction. CONCLUSION:HUTT can be applied to evaluate the autonomic function of children and adolescents with headache and/or dizziness and assess the treatment responses in those patients with autonomic dysfunction.

This cross-sectional study assessed the well-being of family members affected (AFMs) by substance use disorder (SUD) of other family members. Mental symptoms, social avoidance, and quality of life (QoL) were measured for 775 Chinese AFMs and 206 controls. Saliva from 65 AFMs and 31 controls was analyzed for cortisol, BDNF, proBDNF, and mRNA levels of BDNF and its receptors (TrkB, P75NTR, Sortilin). AFMs had significantly higher SCL-90 scores (t = 3.45, p < 0.01) and lower SF-36 scores (t = -4.70, p < 0.01). Of AFMs, 22.1

Accumulating research has demonstrated a significant association between early-life inflammation and behavioral disorders later in life. However, the effects of early-life inflammation on aggressive behavior in adulthood remain poorly understood. Here, we show that early-life inflammation induced by lipopolysaccharide (LPS) upregulated neuronal dynamin-related protein 1 (DRP1) and impaired mitochondrial function in medial prefrontal cortex (mPFC) of adult mice, thereby increasing aggressive behavior in adulthood. We further identify that CCAAT/enhancer binding protein β (C/EBPβ) is the transcription factor of Dnm1l, which was activated by an increased release of lysophosphatidic acid (LPA) induced by early-life inflammation. Moreover, the overproduction of LPA was due to a specific increase in astrocyte-secreted autotaxin (ATX). Specific knockdown of astrocytic ATX reduced early-life inflammation-induced aggression in wild-type mice, but not in Thy1-C/EBPβ transgenic mice. Remarkably, coenzyme Q10 decreased early-life inflammation-induced aggressive behavior in adult mice. Altogether, these findings provide new insights into the molecular mechanisms by which early inflammation promotes aggressive behavior in adulthood.