1. Aboul-Fotouh S, Zohny SM, Hassan GA, Eissa AM, Elshahawi HH, Abdelraouf SM, Ahmed MY, Rabei MR, Hassan FE, Mahmoud AN, Eltantawy EH, Khedr S, Ramadan Y, El-Ashry MK, Elnahas EM. Blockade of NMDA-receptors mitigates autistic and cognitive behaviors via modulation of TLR-4/NLRP3 inflammasomes and microglia/astrocyte crosstalk in rat model of autism. Neurotoxicology. 2025; 111: 103350.

Converging evidence proposed NMDA-receptor dysfunction as a real challenge underlying excitotoxicity implicated in neurological changes of autism spectrum disorder (ASD). Nevertheless, the role of NMDA receptors in relation to toll-like receptor-4 (TLR-4), NOD-like receptor-3 (NLRP3), and microglia/astrocyte activity in autism-related neuroinflammation has not been investigated hitherto. METHODS: The present study was designed to explore the potential role of NMDA-receptor blockade in autism by chronic memantine (MEM) treatment (20 mg/kg/d, i.p.) in male Wistar rats, prenatally exposed to valproic acid (VPA). RESULTS: Prenatal VPA exposure exhibited autistic-like core symptoms and cognitive deficits that were accompanied by gene and protein overexpression of NMDAR-GluN1 & GluN2B subunits, TLR-4, and NF-κB in the prefrontal cortex (PFC). Additionally, VPA increased oxidative/nitrosative stress and inflammasome markers (NLRP3, procaspase-1, and caspase-1). Similarly, histopathological and immunohistochemical studies confirmed neurodegenerative changes, together with microglia/astrocyte reactivity, increased inflammatory and apoptotic markers, along with elevated Ki-67, β-amyloid expression, and the number of neurofibrillary tangles in prefrontal and cerebellar cortices. Chronic treatment with MEM ameliorated the above-mentioned behavioral, neurochemical, and histopathological abnormalities, and interestingly, these effects significantly correlated with NMDAR expression. CONCLUSION: To the author’s knowledge, this study is the first to confirm the potential modulatory effect of NMDA-receptor blockade, via memantine, on TLR-4/NLRP3 inflammasome pathway and microglia/astrocyte crosstalk, in relation to its role in mitigating the autistic behaviors and cognitive deficits in autism. These findings therefore lend further support to the hypothesis that NMDA-receptor blockade may represent a novel and promising pharmacotherapeutic strategy for ASD.

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2. Brothwell J, Jeje O, Mashamaite D, Fanucchi S. Novel interactions between FOXP2 and PAX6: Implications for neural development and autism spectrum disorders. Biochim Biophys Acta Proteins Proteom. 2025; 1874(1): 141110.

FOXP2 and PAX6 are transcription factors essential for neural development, with mutations in both linked to autism spectrum disorders (ASDs). Their DNA-binding domains include a forkhead domain (FHD) for FOXP2 and a paired domain (PD) plus homeodomain (HD) for PAX6. We investigated whether the FOXP2 FHD interacts directly with PAX6 PD or HD, and how such interactions influence DNA binding. Fluorescence anisotropy showed that all three domains bind specifically to their respective DNA targets with similar affinities. The FOXP2 FHD also interacts directly with both PAX6 PD and HD, with low micromolar binding affinities. Despite its stronger intrinsic DNA affinity, the FHD was displaced from its target DNA by both PAX6 domains, suggesting that protein-protein interactions can override DNA affinity under competitive conditions. In contrast, FOXP2 could not displace PD or HD from their DNA targets. Molecular docking supported these findings: DNA-protein interfaces were largely unchanged by the second protein, but protein-protein interfaces were strongly influenced by DNA occupancy. The H3 helix of FHD was identified as a central point for assembly, contributing to both DNA and protein interfaces. When FHD was bound to DNA, H3 was occupied, forcing PD or HD to dock at alternative, less optimal sites. HD maintained stronger contacts in these rearranged states, consistent with its greater competitive strength. This asymmetric interplay indicates competitive dominance by PAX6 and suggests mechanisms that could underlie transcriptional regulation in neurodevelopment.

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3. Carty A, Green R, Goodman CV, McLaughlin JR, Hu H, Lanphear B, Martinez-Mier EA, MacFarlane AJ, Muckle G, Brook JR, Till C. Prenatal fluoride exposure and autistic behaviors in preschool-aged children: the Maternal-Infant Research on Environmental Chemicals (MIREC) cohort study. Environ Health. 2025; 24(1): 87.

BACKGROUND: The prevalence of autism spectrum disorder has risen in recent decades. Given the growing evidence that prenatal fluoride exposure may be neurotoxic, we examined associations between prenatal fluoride exposure and parent-reported autistic behaviors in preschool-aged children. METHODS: We studied 453 mother-child pairs using data from the Maternal-Infant Research on Environmental Chemicals (MIREC) study, a prospective Canadian birth cohort. Autistic behaviors were assessed in children at 3 to 4 years using the Social Responsiveness Scale-Second Edition (SRS-2) Preschool Form, where a higher score indicates more autistic behaviors. We estimated prenatal fluoride exposure using three methods: (i) maternal urinary fluoride adjusted for specific gravity (MUF(SG)), from spot urine samples collected at each trimester and the mean calculated across samples, (ii) daily maternal fluoride intake, based on self-reported consumption of tap water, coffee, and tea during the first and third trimesters, and (iii) water fluoride concentration in tap water. We used multivariable linear regression models to estimate associations between the SRS-2 scale T-scores and each fluoride exposure separately. We used multivariable logistic regression to estimate the association between each prenatal fluoride exposure and an elevated SRS-2 total T-score (i.e., 90th percentile or higher). Potential effect modification of MUF(SG) was examined by child sex, daily folic acid supplementation, and plasma total folate in pregnancy. RESULTS: The mean SRS-2 total T-score for children aged 3 to 4 years was 45.3 (SD = 6.1, range = 34 to 85). The median MUF(SG) concentration was 0.43 mg/L (interquartile range = 0.33 mg/L). MUF(SG) was not significantly associated with the SRS-2 total T-score in multivariable linear regression (β = -0.16; 95% CI, -1.70, 1.39) or logistic regression (OR = 0.76; 95% CI, 0.29, 1.96). Similarly, estimated daily fluoride intake and water fluoride concentration were not associated with the SRS-2 total T-score. No effect modification was observed. CONCLUSIONS: There was no evidence of an association between prenatal fluoride exposure and autistic behaviors in preschool-aged children, in contrast to previous MIREC research findings on lead and phthalates. Given that this cohort has relatively few children with high SRS-2 scores, further research is needed in other groups of children to more fully explore this association.

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4. D’Incal CP, Van Dijck A, Annear DJ, Harutyunyan L, Elinck E, Dingemans AJM, de Vries BBA, Mateiu L, Meuwissen M, Jansen AC, Kooy RF. A frameshift variant in activity-dependent neuroprotective protein (ADNP) causes nucleocytoskeletal alterations in a dizygotic male twin: a case study. Clin Epigenetics. 2025; 17(1): 185.

BACKGROUND: The Helsmoortel-Van der Aa syndrome is an autosomal-dominant neurodevelopment disorder caused by heterozygous de novo variants in the Activity-Dependent Neuroprotective Protein (ADNP) gene, characterized by autism, intellectual disability, dysmorphic facial features, and deficits in multiple organ systems. ADNP is a zinc finger DNA-binding protein that primarily interacts with chromatin remodelers regulating embryonic development, while also associating with components of the cytoskeleton, thereby regulating autophagy and microtubule dynamics during development. In this study, we investigated these nucleocytoskeletal alterations explaining neurodevelopmental delay in a child with Helsmoortel-Van der Aa syndrome who had an unaffected dizygotic twin brother. RESULTS: We performed a genome-wide methylation array on PBMCs from dizygotic twins, showing a predominant CpG hypomethylation episignature. Enrichment analysis of methylated genes revealed significant pathway changes in actin filament organization, Wnt signaling, embryonic development, heart development, and the immune system. In addition, transcriptome sequencing substantiated the affected pathways regulating nuclear and cytoskeletal filamentous alterations associated with autism and neurodevelopmental delay. Brain magnetic resonance imaging showed a mild generalized prominence of the subarachnoid space overlying both hemispheres, revealing intricate patterns of neurodevelopmental delay. CONCLUSIONS: We report the first molecular study performed on dizygotic twins of which one was diagnosed with Helsmoortel-Van der Aa syndrome, revealing Wnt signaling and filamentous cytoskeletal alterations as a potential drug targets for therapy. LIMITATIONS: Indications for neurodegeneration, following these cytoskeletal perturbations, have been observed in cellular and murine models for the Helsmoortel-Van der Aa syndrome. However, clinical evidence remains unclear due to the young age of patients, limiting long-term studies on the aging brain. Further longitudinal imaging studies combined with histopathological autopsy sections are required to study the impact of an ADNP variant in the brain as patients come to age.

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5. Friedman L, Maltman N, Sterling A, Hudock RL, DaWalt LS. Filled Pause Use in Autistic Adults and Their First-Degree Relatives: Gender Differences and Within-Family Associations. J Speech Lang Hear Res. 2025; 68(11): 5399-413.

PURPOSE: Prior research indicates that filled pauses (e.g., um and uh) are a marker of pragmatic language. Although pragmatic language features run in families of autistic individuals, it is not clear whether variation in filled pause production of autistic adults is also familial. It is also possible that filled pause use is a subtle meaningful marker of gender differences. The present study examined filled pause production, a potential marker that may be linked to genetic liability, in autistic adults and their parents, and evaluated relationships with autism traits and the broad autism phenotype (BAP). METHOD: Autistic adults (n = 33 males, 10 females) and their parents (n = 15 fathers, 40 mothers) provided a monologic language sample, which were transcribed and analyzed for filled pauses, including um rate (ums out of total words), uh rate (uhs out of total words), and um ratio (ums out of total filled pauses). RESULTS: Autistic adult males and fathers produced higher rates of uhs and lower um ratios than autistic adult females and mothers, respectively. Among autistic adults, more autism traits were associated with lower um ratios and higher uh rates. Adult-filled pause use was associated with maternal filled pause use and paternal BAP features. CONCLUSIONS: Our findings build on research on gender differences in autism. The association between lower um ratio and more autism traits indicates that um may be a pragmatic marker related to core features of autism. The differential relationships in filled pauses of autistic adults and filled pauses and BAP features of their parents suggest that filled pauses may be familial. Findings have implications for examining the utility of filled pauses as markers of genetic liability for autism.

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6. Fyfe I. Autism profiles differ with age of diagnosis. Nat Rev Neurol. 2025.

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7. Kay MA, Karaca MA, Çelik OT, Kaçmaz C. Difficulties faced by children with autism spectrum disorders after an earthquake: a study from parents’ perspectives. Sci Rep. 2025; 15(1): 39258.

The February 6, 2023 Kahramanmaraş earthquake severely affected 11 provinces in Türkiye, disrupting services for vulnerable groups. This research aims to examine the difficulties that children diagnosed with Autism Spectrum Disorder (ASD) face in education, health, and social support services from the parental perspective following the earthquakes centered in Kahramanmaraş on February 6, 2023. The research used a basic qualitative research method and semi-structured interviews were conducted with 22 parents residing in Malatya, which was affected by the earthquake. The data obtained were examined with content analysis method. Students diagnosed with autism spectrum disorder have been found to experience significant declines in their educational performance, health routines (in adapting to them) and basic skills such as going to the toilet, eating and self-care. At the same time, parents faced difficulties in accessing health and social services. As a result of the research, it was determined that the interruption of the daily routines of children diagnosed with ASD and their alienation from their social environments after the disaster increased behavioral and emotional problems. It was emphasized that alternative education models should be developed for children diagnosed with ASD during disaster periods and families should be encouraged to take an active role in this process. Following disasters, ABA practices, mobile tools and teletherapy should be integrated into technology-based disaster response policies to continue ASD training and therapy.

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8. Kiykim E. Can Folinic Acid Be a Treatment Option for Autism?. Turk Arch Pediatr. 2025.

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9. Lee YL, Shin HI, Bang MS, Shin SH, Kim EK, Lee ES, Jo S, Shin HI, Lee WH. Movement smoothness at term-equivalent age is associated with motor developmental delay in preterm infants. Sci Rep. 2025; 15(1): 39256.

This prospective longitudinal cohort study aimed to quantify limb-movement smoothness at term-equivalent age and investigate whether limb-movement smoothness is associated with motor developmental delay (MDD) in very-preterm or very-low-birth-weight infants. Video recordings of limb movements were obtained at term-equivalent age, and the Bayley Scales of Infant and Toddler Development, Third Edition, was conducted at nine months of corrected age. Upper and lower limb movement smoothness was quantified using a pretrained 2D pose estimator and smoothness indices measured by log dimensionless jerk (LDJ) and spectral arc length (SPARC), with lower LDJ magnitude and less-negative SPARC indicating smoother movement. The quantified movement smoothness was compared between infants with and without MDD. Among 111 infants, 11 (9.9%) exhibited MDD. The LDJ measurements showed significant differences at the right shoulder, elbow, hip, knee, and left elbow between infants with and without MDD (p < 0.05, d ≈ 0.96-1.12). The SPARC measurements showed significant differences at the right shoulder, hip, knee, and left knee between the two groups (p < 0.05, d ≈ 0.64-0.89). The motor composite scores showed significant positive correlations with the absolute values of LDJ and SPARC at the multiple joints. Limb-movement smoothness at term-equivalent age is associated with MDD in very-preterm or very-low-birth-weight infants. Smoothness indices of limb movements can be potentially useful for the early detection of MDD.

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10. Mendes MSS, Barlow P, Jardini MAN, de Oliveira AGL, Bulgarelli AF, Tôrres L, Guimarães MB, Pinto LR, de Menezes EEG, Nogueira TE, Marchini L. Large-Scale Psychometric Analysis of the Brazilian Ageism Scale for Dental Students (ASDS-Braz)-A Multicenter Study. Spec Care Dentist. 2025; 45(6): e70113.

PURPOSE: To reassess the psychometric properties of ASDS-Braz in a large, multicenter sample of Brazilian dental students, aiming to evaluate its factorial structure’s robustness and applicability across diverse contexts. METHODS: Data were collected around 2 years from multiple Brazilian centers, including responses to the ASDS-Braz and demographic variables, and additional questions regarding participants’ experience living with or caring for older adults, as well as their clinical course experience. Data were consolidated for large-scale validation through secondary analysis. Exploratory factor analysis (EFA) was conducted, with factorability assessed using the Kaiser-Meyer-Olkin (KMO) measure and Bartlett’s test. Principal Axis Factoring with Varimax rotation was applied, and internal consistency was evaluated using Cronbach’s alpha. Analyses were performed using SPSS v.28, with p < 0.05 considered statistically significant. RESULTS: The sample included 1539 dental students from 11 schools, predominantly white (66.3%) and female (72.4%), with most having clinical experience (87.4%). The ASDS-Braz was divided into four factors, with Factors 1 and 2 showing moderate reliability (α = 0.71) given the size of the study. However, other factors and the 10-item scale did not meet the acceptability threshold. CONCLUSION: The ASDS-Braz did not exhibit satisfactory psychometric properties in a large, multicenter sample. It requires restructuring, refinement, and revalidation to ensure its suitability for national research and clinical application in Brazil.

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11. Meng S, Guo S, Huang Z, Sun Z, Han S, Han Y, Tong W, Qi K. Research hotspots and trend analysis of motor dysfunction in children with autism spectrum disorder based on CiteSpace. Comput Biol Chem. 2025; 120(Pt 1): 108776.

Motor dysfunction is a prevalent yet often overlooked characteristic in children with Autism Spectrum Disorder (ASD), impacting their daily functioning and overall development. This study employs bibliometric methods to systematically examine the research landscape of motor dysfunction in children with ASD, aiming to identify evolving trends, key focus areas, and future directions. Using CiteSpace software, we conducted a visual analysis of 2602 articles published between 2015 and 2025 from the Web of Science Core Collection. Key findings include: (1) The volume of publications experienced fluctuations, with peaks in 2017 and 2022, followed by a projected decline; (2) Leading contributing disciplines include psychology, neuroscience, and rehabilitation, with the United States, China, and Italy as the most productive countries; (3) Research hotspots center on developmental characteristics, neural mechanisms, and intervention strategies for motor dysfunction; (4) The research focus has evolved through three distinct phases: early emphasis on developmental traits, interim exploration of associations with core ASD symptoms, and recent prioritization of intervention development. These findings not only map the intellectual structure and dynamic progress in this field but also provide a foundational reference for guiding future research, clinical practice, and cross-disciplinary collaboration.

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12. Wang Y, Wang Q, Li R, Yu Y, Feng S, Wu W, Ren S. Microglial TREM2 deficiency causes E/I imbalance and triggers ASD-like behaviors by altering potassium channel Kv1.3 activation. Neurobiol Dis. 2025; 217: 107185.

Autism Spectrum Disorder (ASD) is a type of neurodevelopmental disorder characterized by deficits in social interaction and stereotyped behavior, with synaptic dysfunction playing a causal role in its pathogenesis. Microglia, as innate immune cells in CNS, are involved in regulation of synaptic transmission and plasticity through directly pruning spines and indirectly releasing bioactive substances. Interestingly, loss-of-function of triggering receptor expressed on myeloid cells 2 (TREM2), a key receptor in regulation of microglial immune functions, has been implicated in neurodevelopmental and neurodegenerative diseases through altering synaptic transmission and neuronal homeostasis. However, it is currently still not well established how TREM2 loss-of-function causes those effects. Here, we found that TREM2 deficiency during early postnatal stage led to an increased Kv1.3 channel activity in microglia, which resulted in an imbalance of excitatory and inhibitory synaptic transmissions (E/I imbalance) characterized by increased mEPSCs and reduced mIPSCs frequencies, leading to neuronal hyperactivity in neocortex. Importantly, Kv1.3 conditional knock-out and specific pharmacological inhibition effectively restored the E/I imbalance and neuronal hyperactivity, and alleviated ASD-like behaviors in TREM2-deficient mice. Together, our findings suggest that the increased Kv1.3 activity may underlie the neuronal dysfunction and behavioral deficits associated with TREM-2 deficiency, highlighting Kv1.3 as a potential therapeutic target for ASD treatment.

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13. Wise J. Paracetamol (Tylenol): No clear link between use in pregnancy and autism or ADHD in children, rapid review finds. Bmj. 2025; 391: r2368.

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