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Cannabis is one of the most widely used drugs in early adolescence, a crucial time for development. Cannabinoids within the cannabis plant (e.g., delta-9-tetrahydrocannabinol [THC], and cannabidiol [CBD]) are suggested to have a range of health implications. These may differ by sex, given sex differences in the endocannabinoid system (ECS). Yet, how aspects of mental and physical health are related to cannabis use as measured by hair concentrations, both within early adolescence and across sexes, is so far inconclusive. We analyzed hair toxicology data from three cannabinoid analytes (THC, CBD, and 11-nor-9-carboxy-THC [THCCOOH]) and multiple mental and physical health measures in 9-15 year-old youth (49 % female) from the Adolescent Brain Cognitive Development (ABCD) Study (N = 2262). Two-part linear regression models were fit to assess the effects of cannabis constituent presence, concentrations, and THC concentrations + CBD presence on externalizing and internalizing symptoms, physical and strengthening exercise, asthma presence, and sleep duration. Secondary analyses fit the same models but stratified by sex. Finally, to further characterize these relationships, we conducted two exploratory analyses: we assessed health variables prospectively and concurrently predicting cannabinoid concentrations. False discovery rate corrections were employed for all analyses. In the full sample, greater THC concentrations predicted more frequent strength exercise one year later; greater CBD concentrations predicted fewer strength exercise days; and greater THCCOOH concentrations predicted shorter sleep duration. Among males, cannabinoids differentially predicted exercise days; greater THC and THCCOOH concentrations predicted shorter sleep duration. Among females, greater THC and THCCOOH concentrations predicted strength exercise frequency, and THC concentrations predicted shorter sleep duration. In exploratory models, asthma presence predicted THCCOOH concentration one year later. Concurrently, THC concentration alone and in the presence of CBD predicted both sleep duration and lower exercise days, while THCCOOH concentration predicted lower exercise days, less asthma presence, as well as greater internalizing and externalizing symptoms. In a nationwide study of youth ages 9-15 years old, we found cannabinoid hair concentrations predicted differences in health outcomes a year later, suggesting potential differential mechanisms for THC and CBD effects on health. Furthermore, sex-specific observations in these prospective associations emphasize the importance of considering sex assigned at birth when investigating correlates of cannabis use. Analysis of cannabinoid hair concentrations can reveal key links to mental health, physical activity, and sleep, aiding understanding of complex cannabis effects.
Cannabis and tobacco are contaminated with insecticides and used during pregnancy in the U.S., raising concerns for co-exposures and compounded neurodevelopmental effects. However, these cumulative effects remain unexplored. We examine the associations of prenatal cannabis, tobacco, pyrethroid, and organophosphate insecticides co-exposures with early childhood neurobehaviors. Among 197 mother-child pairs from a birth cohort in Atlanta, Georgia, cannabis (THCCOOH), tobacco (COT and 3OH-COT), pyrethroids (3PBA), and organophosphates (TCPY) metabolite levels were quantified in maternal urine sampled at 8-14 and 24-30 weeks' gestation. Infant arousal and attention were evaluated 2 weeks postnatally using the NICU Network Neurobehavioral Assessment Scale. Externalizing and internalizing behaviors were assessed annually using the Child Behavior Checklist and averaged across ages 2-5 years. We examined individual associations using linear regression; cumulative associations using quantile g-computation and Bayesian kernel machine regression (BKMR); and whether THCCOOH modified the cumulative effect of tobacco and insecticides. Of the prenatal exposures, only insecticides were associated with child neurobehavior. For example, a doubling in 3PBA was positively related to internalizing behaviors (β = 18.1 %; 95 % confidence interval [CI] = 0.0 %, 39.5 %), and TCPY was negatively associated with externalizing behaviors (β = -12.9 %; 95 % CI = -27.8 %, 5.0 %). These were modified by THCCOOH and sex. The prenatal 3PBA, TCPY, COT, and 3OH-COT mixture was associated with lower externalizing behaviors among females with detectable THCCOOH (quantile g-computation β = -46.8 %; 95 % CI = -70.4 %, -4.1 %). BKMR showed no interactions and dose-responses. Prenatally, 3PBA and TCPY were associated with child neurobehaviors, and effects differed by THCCOOH and sex. Further studies on the neurodevelopmental burden of cannabis, tobacco, and insecticide co-exposures are needed.
To investigate the anti-apoptosis and anti-ferroptosis effects of dl-3-n-butylphthalide (dl-NBP) on cerebral ischemia-reperfusion injury (CIRI) in rats, and the potential involvement of cysteine-X-cysteine chemokine receptor 4 (CXCR4). The differentially expressed genes between healthy people and stroke patients were screened by GEO database. A transient middle cerebral artery occlusion rat model was used to induce CIRI in vivo. Rats were randomly divided into sham group, tMCAO group, and dl-NBP + tMCAO group. The therapeutic effect of dl-NBP in vivo and its effect on apoptosis and ferroptosis in brain tissues were evaluated. An in vitro oxygen-glucose deprivation/reperfusion (OGD/R) model was established to simulate CIRI in cultured PC12 cells, and the effects of dl-NBP on apoptosis and ferroptosis were examined. In this model, CXCR4 expression was assessed by western blotting and its involvement in dl-NBP-mediated protection assessed by inhibition with AMD3100. In the stroke-related GSE22255 and GSE66724 datasets, a total of six genes with increased co-expression were found, including CXCR4. Dl-NBP treatment significantly reduced both the volume of cerebral infarction and the degree of cerebral edema, and improved neurological function in rats. dl-NBP reduced the degree of apoptosis and ferroptosis and alleviated CIRI both in vivo and in vitro. The pro-survival effects of dl-NBP were significantly reversed after CXCR4 inhibition with AMD3100. Dl-NBP has anti-apoptotic and anti-ferroptotic effects on CIRI both in vivo and in vitro, and this effect is mediated by CXCR4.
Prenatal cocaine exposure (PCE) can alter the monoaminergic neurotransmitter system in the fetal brain related to emotional and behavioral regulation. PCE has been associated with high rates of aggression and delinquency, risk for victimization, and multiple environmental stressors associated with a disadvantaged environment, including postnatal lead exposure. While postnatal lead exposure has also been linked to aggressive behavior/delinquency, little is known about the combined impacts of PCE and lead on behavior, nor how they interact with environmental stressors such as victimization. Assess the relationships of PCE, postnatal lead levels, and victimization to adolescent self-report of aggressive behavior/delinquency, controlling for other prenatal drug exposures and the quality of the caregiving environment. At age 17, 336 adolescents (50 % PCE, 46 % male) reported their aggressive behavior/delinquency (AGG) on the Problem-Oriented Screening Instrument for Teenagers, and type of lifetime victimization on the Juvenile Victimization Questionnaire. Blood lead levels were measured at 2-4 years, and the Home Observation for the Measurement of the Environment - Early Adolescence at 15 years. Binomial logistic, multiple regression and mediation analyses examined group differences and relationships among variables. PCE, victimization (child maltreatment and peer/sibling victimization), and postnatal lead levels were each associated with higher AGG. Girls with PCE reported higher AGG than non-exposed girls while boys did not differ, and all adolescents with PCE reported more child maltreatment and peer/sibling victimization. Child maltreatment partially mediated the relationship between PCE and aggressive behavior/delinquency. Recognition of the higher rates of maltreatment and peer/sibling victimization with PCE is important for intervention efforts, as each contributes to higher AGG. As PCE may be associated differentially with higher AGG in girls, gender-focused interventions should be considered while addressing the increased impact of victimization and postnatal lead levels on AGG in both PCE and NCE boys and girls.
Fetal Alcohol Spectrum Disorder (FASD) represents a major global public health concern, affecting approximately 7.7 per 1000 births worldwide and remains as the most common preventable cause of lifelong neurodevelopmental impairment. Despite its prevalence, current clinical interventions are largely symptom-supportive and fail to address the underlying developmental pathology, underscoring the need for targeted, mechanism-based therapeutic strategies. Given the central involvement of oxidative stress and inflammation in FASD pathogenesis, this study evaluated the protective efficacy of S-adenosyl-L-methionine (SAMe), a key metabolic intermediate and universal methyl donor, using a zebrafish embryo model because of its high translational relevance and optical transparency. Fertilized embryos were exposed to 1.25% ethanol and co-treated with SAMe (15 and 30 μM) until 96 h post-fertilization (hpf). Ethanol exposure resulted in reduced survival and hatching rates, cardiac rhythm abnormalities, pronounced morphological defects, and compromised tissue integrity. SAMe treatment, particularly at 30 μM, significantly ameliorated these developmental abnormalities and associated biochemical dysregulations. Mechanistically, SAMe exerted a dual protective effect by restoring glutathione biosynthesis and attenuating oxidative stress-driven inflammatory responses. This was evidenced by marked reductions in reactive oxygen species, apoptosis, lipid peroxidation, and nitric oxide levels, alongside significant downregulation of pro-inflammatory cytokines, including TNF-α and IL-1β. Importantly, these biochemical and molecular improvements were consistently translated into phenotypic rescue, with substantial normalization of tissue architecture and developmental morphology. Collectively, these findings establish SAMe as a promising anti-teratogenic intervention that directly targets core oxidative and inflammatory pathways underlying FASD, highlighting its potential translational relevance as a mechanism-driven therapeutic strategy.
Excessive exposure to monosodium glutamate (MSG) induces glutamate-mediated excitotoxicity, oxidative stress, and neuroinflammation, culminating in neurobehavioral impairments. Bromelain, a cysteine protease derived from Ananas comosus, exhibits potent antioxidative and anti-inflammatory properties; however, its potential to attenuate excitotoxic neuronal injury remains insufficiently characterized. This study investigated the neuroprotective effects of bromelain against MSG-induced neurotoxicity through integrated behavioral, biochemical, histological, and computational analyses. Male Swiss mice (7-8 weeks) received MSG (4 g/kg, i.p.) to induce excitotoxicity and were subsequently treated orally with bromelain (50 or 100 mg/kg) or fluoxetine (1 mg/kg) for 21 days. Behavioral tests assessed locomotor, cognitive, and affective functions, while biochemical and histological analyses evaluated oxidative stress, neuroinflammatory markers, and neurotransmitter-modulating enzyme activities. In silico AlphaFold3 modeling and protein-protein docking were employed to elucidate bromelain's interactions with acetylcholinesterase (AChE), monoamine oxidase-B (MAO-B), and glutamate decarboxylase (GAD). Bromelain treatment significantly ameliorated MSG-induced behavioral deficits, restored cortical and hippocampal redox balance, suppressed pro-inflammatory cytokines, and preserved neuronal cytoarchitecture. It normalized neurotransmitter metabolism by inhibiting AChE and MAO-B activities while enhancing GAD function. AlphaFold3 modeling revealed a compact, high-confidence bromelain conformation (pLDDT >90) with strong predicted binding affinities to catalytically active residues of AChE, MAO-B, and GAD, supporting its multi-target neuromodulatory role. Altogether, these findings provide the first integrated experimental and computational evidence that bromelain confers neuroprotection by regulating redox homeostasis, inflammation, and neurotransmitter signaling, highlighting its promise as a nutraceutical candidate for mitigating glutamate-mediated neurodegenerative disorders.
Growing evidence challenges the long-standing assumption that the paternal germline is insulated from environmental perturbation and identifies preconception paternal exposure as an underrecognized pathway of developmental neurotoxicity. Across mammalian models, paternal exposure to substances of abuse, including cocaine, nicotine, ethanol, morphine, and cannabinoids, induces reproducible, often sex-specific alterations in offspring brain function and behavior, including changes in cognition, stress responsivity, reward processing, and affective behaviors, accompanied by transcriptional and epigenetic modifications. A critical but underappreciated determinant of these outcomes is exposure design, particularly exposure duration relative to the spermatogenic cycle, which emerges as a primary toxicodynamic relevant variable. Exposures spanning a full spermatogenic cycle frequently produce persistent neurobehavioral and molecular alterations, whereas shorter exposures targeting late spermatids or mature sperm can also generate robust offspring phenotypes, highlighting stage-specific germ cell vulnerability. Importantly, delaying mating beyond a complete spermatogenic cycle often attenuates offspring effects, suggesting that temporal separation between exposure and conception may mitigate neurodevelopmental risk. Mechanistically, paternal exposures disrupt sperm epigenetic regulation, including altered DNA methylation, histone modifications, and small RNA profiles, often linked to germline oxidative stress as a potential upstream mediator. Exposure dose and route further modulate transmission through pharmacokinetic effects on systemic and germline exposure. We propose a stage-specific framework in which paternal transmission magnitude and persistence are primarily determined by exposure duration relative to spermatogenesis, with dose and route acting as key modifiers. This framework integrates behavioral and molecular findings and provides a biologically grounded basis for developmental neurotoxicity risk assessment and male preconception health.
Pediatric neurotoxicity remains a major cause of morbidity and mortality in low- and middle-income countries. In Morocco, the burden of toxic exposures leading to neurological disorders is still underexplored. This study aimed to describe the epidemiology, clinical profile, toxicological features, and outcomes of pediatric neurotoxic poisonings in a tertiary care hospital in Fez, Morocco. A prospective cross-sectional study was conducted from January 2021 to January 2023 at the Pediatric Emergency Units of Hassan II University Hospital. Pediatric patients under 18 years presenting with neurological symptoms secondary to confirmed or suspected toxic exposures were included. Demographic, clinical, and toxicological data were collected using standardized forms, complemented by biological sampling and advanced toxicological analyses. Among 4183 pediatric emergency admissions, 743 (17.8%) presented with neurological disorders, of which 384 (51.7%) were attributed to toxic exposures. Of these 384 cases, major agents included pharmaceuticals, traditional herbal remedies, pesticides, venoms, and illicit substances. Multiple exposures were observed in 55% of cases, and 70% resulted from repeated exposure. Intensive care was required in 29.1% of patients, and overall mortality reached 11.9%, with phytotherapy, illicit drugs, and pesticides being the leading causes of death. Delayed consultation and limited antidote availability were major challenges. Pediatric neurotoxicity is highly prevalent in Morocco, shaped by a unique combination of cultural and environmental risk factors. These findings underscore the urgent need for strengthened toxicovigilance, regulation of hazardous substances, public education, and improved diagnostic and therapeutic resources.
In the brain, alcohol metabolites alter the functioning of several neurotransmission systems, such as glutamatergic and cholinergic, in addition to impairing memory and learning. Medications for Alcohol Use Disorders (AUD) cause adverse effects and contraindications. N-acetylcysteine (NAC) has been shown to protect memory and restore acetylcholinesterase (AChE) levels. Additionally, it functions as an antioxidant that works alongside glutathione, which is associated with the glutamatergic synapse. In this context, the current research aimed to examine the neuroprotective effects of NAC in animals that underwent repeated ethanol exposure (REE), along with the impacts on memory and the cholinergic and glutamatergic signaling pathways in zebrafish. The animals were exposed to 1 % ethanol for 8 days for 20 min daily. They received treatment with NAC after the eighth exposure to ethanol for 10 or 60 min. Euthanasia occurred 24 h after the last exposure. Inhibitory avoidance and object recognition tests were performed. Also, the choline acetyltransferase (ChAT) enzyme activities, AChE activity, and glutamate uptake were evaluated. The results show a significant AChE activity increase in the REE group and a decrease in those exposed to alcohol and treated with NAC for 10 min. No significant differences were found regarding ChAT activity. REE significantly reduced glutamate uptake. All groups except the ethanol group acquired aversive memory in inhibitory avoidance tests. Only the NAC-treated group demonstrated longer new object exploration in the recognition test. The study indicates that REE affects AChE, glutamate uptake, and aversive memory and that a single NAC treatment can mitigate these effects. These findings enhance the understanding of REE mechanisms and NAC's protective properties against ethanol-induced damage in zebrafish.
Attention deficit hyperactivity disorder (ADHD) occurs in 9.8% of U.S. children and has a large hereditary component arising from multiple gene variants. One of these is Latrophiln-3 (LPHN-3). Using CRISPR/Cas9 we deleted exon 3 in Sprague Dawley rats to create a global Lphn3 knockout (gKO). The gKO rats are hyperactive, startle hyper-reactive, impulsive, and have impaired working, spatial, and egocentric learning and memory. Permethrin (PRM) is a widely used pyrethroid insecticide. Acute exposure to PRM alters acoustic startle but its long-term effects from developmental exposure are unknown. The present experiment tested whether Lphn3 heterozygosity interacts with PRM developmental exposure to affect post exposure neurobehavior in rats. We used Lphn3+/- (Het) rats since they have an intermediate phenotype compared with gKO rats that are severely affected (Regan et al., 2022). There were 4 groups: Lphn3-Het + PRM (120 mg/kg daily by gavage from postnatal day (P) 6-20 in 5 mL/kg corn oil (CO)), Lphn3-Het + CO, wildtype (WT) + PRM, and WT + CO. From 25 litters, 20-22 males and 20-22 females of each combination were obtained with not more than one male and one female from any given litter. Adult offspring were tested in an automated open-field for 1 h, in home-cage activity for 72 h, startle (including prepulse inhibition), novel object recognition (NOR), working memory (radial water maze (RWM)), spatial learning (Morris water maze (MWM)), and egocentric learning in the Cincinnati water maze (CWM). On acquisition and reversal probe trials in the MWM and on learning trials in the CWM, Lphn3-Het-PRM rats performed worse than other groups. In open-field, home-cage, startle, NOR, and RWM there were no interactions between Lphn3 and PRM but there were effects of Lphn3 heterozygosity. The results indicate that heterozygosity of the ADHD risk gene Lphn3 when combined with developmental exposure to PRM increases the adverse effects of either one alone.
Periconceptional and prenatal tobacco exposure (PPTE) has been associated with early externalizing behaviors, yet the developmental pathways underlying this association remain poorly understood. The purpose of this study was to examine potential mechanisms through which PPTE may relate to child behavior. Data were drawn from a prospective, longitudinal cohort of mother-child dyads recruited at birth. The final sample included 203 mothers, predominantly White, with lower income, education, and partnership rates observed among heavier smoking groups. The study collected socio-demographic information and measures of maternal psychological distress, child language ability and behavior. PPTE, defined in this study as a continuous variable representing the average number of cigarettes smoked per day three months prior and during pregnancy, was the primary exposure variable. Maternal psychological distress and child language development were evaluated as potential intervening pathways. A path model was used to evaluate the relative contribution of direct and indirect effects of PPTE on externalizing behavior at 24-months. PPTE significantly predicted both greater maternal psychological distress and poorer child language ability. Both variables were associated with higher externalizing behaviors. In the indirect effects model, the direct effect of PPTE on externalizing behaviors was nonsignificant, while multiple indirect pathways were significant, including via child language development and maternal psychological distress. Findings suggest that the association between PPTE and externalizing behaviors may operate indirectly through maternal psychological distress and child language development.
Microcephaly, a condition characterized by a head circumference below the mean for age and sex, is a significant indicator of impaired fetal brain development. While some environmental factors have been associated with the development of microcephaly in Africa, the available information remains disjointed, making it difficult for healthcare providers and policy makers to translate the information to preventive measures in maternal and child health. This systematic review aims to synthesize primary studies on environmental determinants of microcephaly, focusing on African populations. A systematic literature search was conducted using PubMed, Scopus, AJOL, and Wiley Online Library to identify studies published between 2000 and 2025, focusing on environmental exposures and microcephaly in neonates and infants. Observational and interventional studies in English were included, following PRISMA 2020 guidelines. Data were extracted and tabulated by country, exposure type, study design, and reported outcomes. Sixteen African studies found a multifactorial relationship between environmental exposures and microcephaly. Zika virus infection was a consistent contributor, with maternal febrile illnesses, inadequate antenatal care, HIV exposure, and heavy metal toxicity also linked. Pesticide exposure, particularly to organophosphates and DDT, was associated with neurodevelopmental delays and restricted cranial growth. Ambient air pollution was negatively correlated with neonatal head circumference. Socioeconomic vulnerabilities intensified these environmental risks, especially during epidemic crises like Zika virus outbreaks. Microcephaly in African populations is a multifactorial issue, influenced by emerging infections like ZIKV, chronic environmental exposures, and healthcare gaps. It calls for integrated public health strategies, including surveillance, early prenatal screening, environmental regulation, and region-specific diagnostic standards. Global evidence supports shared biological vulnerability in low-resource settings.
Neurodegenerative diseases and cognitive impairments represent significant global health challenges, necessitating the exploration of alternative and complementary therapeutic options. Herbal remedies, known for their bioactive compounds, have garnered attention for their potential neuroprotective and cognitive-enhancing effects. This review focuses on three widely studied herbal agents, including St. John's Wort (Hypericum perforatum), Green Tea (Camellia sinensis), and Ashwagandha (Withania somnifera) and evaluates their mechanisms in promoting brain health. St. John's Wort has demonstrated potential in alleviating symptoms of depression and anxiety, which are often linked to cognitive decline. Green Tea, rich in polyphenols such as epigallocatechin gallate (EGCG), has shown promise in improving memory function and providing antioxidant protection against neurotoxicity. Ashwagandha, an adaptogenic herb, is recognized for its neuroprotective properties, including reducing stress-induced cognitive deficits and promoting neuronal regeneration. The neuroprotective and cognitive-enhancing effects of these herbs are attributed to their antioxidative, anti-inflammatory, and neurotrophic properties, which collectively may support brain function and mitigate age-related cognitive decline.
Exposure to ambient air pollution, including fine particulate matter (PM2.5), nitrogen dioxide (NO2), and elemental carbon, has been associated with worse neurodevelopmental outcomes in children, but research on early childhood outcomes is limited. This study examined the associations between gestational and early childhood exposures to PM2.5 and NO2 and child developmental outcomes measured at ages 1, 2, and 3 years. In the Health Outcomes and Measures of the Environment (HOME) Study, a longitudinal pregnancy and birth cohort, we used spatiotemporal models to estimate the concentration of each air pollutant at participants' home addresses during early brain development. Neurodevelopmental outcomes were measured using the Bayley Scales of Infant Development, Second Edition (BSID-II) at ages 1, 2, and 3 years. For 329 children, we examined the associations of air pollution with BSID-II scores using generalized linear models with generalized estimating equations (GEE). Gestational and early childhood NO2 concentrations were positively associated with cognitive development at age 1 year but negatively associated with cognitive development at age 3 years. Similarly, PM2.5 exposure through age 3 years was negatively associated with cognitive development at age 3 years. Gestational NO2 concentration was positively associated with motor development at age 1 year but negatively associated with motor development at ages 2 and 3 years. These results suggest that exposure to traffic-related air pollution during gestation and after birth may impact neurodevelopment in early childhood.
Salvianolic acid A (SAL A), a polyphenolic compound derived from Salvia miltiorrhiza, exhibits several neuroprotective effects, but its sedative potential is unexamined. This study explores the sedative effects of SAL A and its potential to modulate the impacts of diazepam (DZP) in a thiopental sodium (TS)-induced sleep model in Swiss albino mice. Mice received intraperitoneal (i.p.) doses of SAL A (5 and 10 mg/kg) and DZP (2 mg/kg), followed by TS (20 mg/kg), with sleep latency and duration recorded. Molecular docking and in silico analyses evaluated SAL A's interaction with the GABAA receptor (α1 and β2 subunits) (PDB ID: 6X3X) and its pharmacokinetic properties. Results revealed that SAL A significantly (p < 0.05) reduced sleep latency and prolonged sleep duration dose-dependently, with 10 mg/kg showing the strongest effect (latency: 14.29 ± 3.09 min; duration: 175.71 ± 18.97 min; Cohen's d = 4.37 and 1.60, respectively). Combined therapy with SAL A-10 and DZP-2 synergistically enhanced sleep duration, with the highest effect sizes observed (d = 5.45 for latency; 4.36 for duration). Molecular docking studies revealed that SAL A showed similar binding affinity (-8.7 kcal/mol) with 6X3X, comparable to DZP. SAL A also exhibited favorable pharmacokinetic properties and low toxicity. These findings suggest SAL A as a potential novel sedative agent with synergistic effects alongside DZP. However, SAL A's poor blood-brain barrier permeability and need for structural optimization highlight the necessity for future mechanistic studies, enhanced delivery methods, and clinical validation to confirm its therapeutic potential for sleep disorders.
Despite the growing recognition of the impacts of microplastics (MPs) and the intensification of extreme weather events, recent investigations have focused mainly on the consequences of global warming, while overlooking the potential impacts of extreme low-temperature (ELT) events and their interaction with these pollutants. Accordingly, the aim of this study was to assess the integrated effects of co-exposure to environmentally aged polystyrene microplastics (PS-MPs) and ELTs on behavioral, neuroendocrine, metabolic, and histomorphometric biomarkers in female Swiss mice. To this end, animals were orally exposed to environmentally aged PS-MPs (10 mg/kg/day) and maintained in a climate-controlled chamber at 4 °C for 21 days, whereas control groups were kept at 25 °C. In the behavioral domain, co-exposed animals exhibited increased locomotor disorganization, anxiety-like behavior, reduced exploratory efficiency, and impairments in memory and social discrimination, associated with neuroendocrine alterations involving dopamine, serotonin, epinephrine, and corticosterone, depending on the response evaluated. The retention of PS-MPs in the interscapular brown adipose tissue (iBAT) was confirmed by epifluorescence microscopy. It was associated with oxidative stress, decreased antioxidant defenses, and metabolic dysfunction in iBAT, effects exacerbated by ELT exposure. Multivariate analyses, including principal component analysis (PCA), Random Forest, and structural equation modeling (PLS-PM), revealed distinct phenotypic patterns among groups, as well as integrated causal trajectories linking neuroendocrine dysfunction to systemic phenotypic alterations. In conclusion, our study confirms the initial hypothesis by demonstrating that the combination of ELT and PS-MP ingestion amplifies systemic physiological dysfunctions beyond the effects of each individual stressor, highlighting the vulnerability of homeothermic mammals under multiple environmental pressures, and opening new perspectives for ecotoxicology to consider not only the impacts of global warming, but also the deleterious effects of ELTs in interaction with emerging pollutants.
Prenatal polysubstance exposure is highly prevalent among individuals with fetal alcohol spectrum disorders (FASD), yet little research has examined how specific patterns of co-exposure relate to neuropsychological outcomes. While alcohol is a known teratogen, other substances such as opioids, stimulants, cannabis, and nicotine also disrupt neurodevelopmental processes. Prior studies often assess single substances in isolation, failing to reflect real-world exposure patterns. Identifying meaningful patterns of co-occurring exposures and their associations with neuropsychological outcomes is critical for advancing targeted assessment and intervention. Latent class analysis was conducted on data from 635 youth with FASD (mean age of diagnosis 7.4 years, range 0.24-21.61) to identify distinct profiles of prenatal exposure to six substances: alcohol, nicotine, marijuana, opioids, cocaine, and other drugs. Class differences in neuropsychological functioning, postnatal experiences, and demographics were examined using the Bolck, Croon, and Hagenaars method. A three-class solution demonstrated best model fit (AIC = 3945.216, saBIC = 3970.790, aLRT = 18.521, p = .006). Classes comprised of an all-exposure (Class 1, 47%), mainly alcohol exposed (Class 2, 46%), and mainly opioid exposed (Class 3, 7%). Significant between-class differences emerged across domains of memory, motor speed, sensory processing, and child-reported anxiety (χ2 = 9.264-42.659, p = .046-0.001). Class 2 demonstrated significantly greater neuropsychological challenges, while Class 3 demonstrated high sensory sensitivity and anxiety. Results also reveal caregiver disruption was more prevalent in Class 2. Findings highlight heterogeneity in neuropsychological outcomes based on distinct patterns of prenatal polysubstance exposures. Neuropsychological assessment remains essential for capturing this variability and informing individualized, exposure-responsive care.
Cadmium, a Group 1 carcinogen, represents a significant public health concern due to its widespread environmental distribution and exposure through industrial processes, contaminated water, dietary intake, and tobacco use. Prolonged cadmium exposure is associated with systemic toxicity, including neurodegenerative outcomes mediated by oxidative stress, protein misfolding, neuroinflammation, and mitochondrial dysfunction. Disruption of autophagy and MAPK signalling pathways (ERK, JNK, and P38) further impairs neuronal function. Cadmium-induced misfolding of key proteins such as tau, amyloid-β, and α-synuclein is implicated in Alzheimer's and Parkinson's diseases. This systematic review aims to map the role of cadmium exposure in neurodegenerative disorders, with a focus on oxidative stress, protein misfolding, autophagy dysregulation, and MAPK signalling pathways. A thorough literature search was conducted across databases including PubMed, Scopus, and Science Direct using specific keywords. Elevated markers, including IL-6, IL-8, and cytochrome c, may serve as diagnostic indicators of cadmium-associated neurodegeneration.