Pubmed du 21/09/25
1. Denusik L, Miletic K, Cunningham BJ, Binns A, Oram J. Maximizing the use of practice-based clinical data to track social communication development in autistic preschoolers. J Commun Disord. 2025; 118: 106575.
PURPOSE: Evaluating caregiver-delivered programs in clinical settings is necessary to generate practice-based evidence. One challenge of such research is the burden placed on clinicians to complete additional measurement tools. This exploratory study examined the validity of clinical forms already completed as part of the standard delivery of the More Than Words® (MTW) program and explored whether this clinical data would reveal distinct clinical and outcome profiles in real-world contexts. METHOD: The Social Communication Checklist (SCC), a MTW program-specific form completed by the speech-language pathologist, was collected for 36 autistic preschoolers during publicly funded delivery of MTW. We assessed the concurrent validity of autistic preschoolers’ social communication stage and skills rated on the SCC pre- and post-program with two of their scores on reliable, validated tools: the Communication Function Classification System (CFCS) and the Focus on the Outcomes of Communication Under Six (FOCUS-34). We also explored autistic preschoolers’ communicative participation outcome profiles on the FOCUS-34 with their assigned social communication stages on the SCC. RESULTS: Autistic preschoolers’ pre-program social communication stage on the MTW SCC correlated with their pre-program CFCS communication level and FOCUS-34 score. Most children showed positive social communication changes post-program according to the SCC, and two-thirds showed meaningful or possibly meaningful clinical change on the FOCUS-34; however, scores on these measures did not correlate. Autistic preschoolers at different pre-program SCC stages showed distinct communicative participation outcome profiles on the FOCUS-34. CONCLUSION: Program-specific clinical forms like the SCC can be valuable for classifying autistic preschoolers’ social communication skills, exploring differences in outcomes, capturing novel outcomes, and generating practice-based evidence.
Lien vers le texte intégral (Open Access ou abonnement)
2. Guiotto A, Vallese A, Cordone V, Cervellati F, Benedusi M, Hayek J, Pecorelli A, Valacchi G. Lipid peroxidation-induced cell death in Rett syndrome. Free Radic Biol Med. 2025.
Rett Syndrome (RTT) is a rare neurodevelopmental disorder, primarily affecting girls (1:10,000 live births), largely caused by mutations in the X-linked gene MECP2, an epigenetic regulator encoding for the methyl-CpG binding protein 2 (MeCP2). Recent evidence links ferroptosis, an iron-dependent cell death characterized by lipid peroxide accumulation, to neurodegenerative and neurodevelopmental disorders like autism. Several RTT hallmarks, including redox imbalance, excess labile iron, increased lipid peroxidation, and impaired antioxidant enzyme activity, align with ferroptosis characteristics. Therefore, we investigated ferroptosis’s role in RTT using human primary fibroblasts from healthy and RTT subjects, treating them with ferroptosis inducers: erastin and RSL3. Our findings show RTT cells are highly susceptible to ferroptosis, marked by elevated lipid peroxidation and mitochondrial reactive oxygen species (mtROS) production, crucial for ferroptotic cell death. We also observed altered iron metabolism and dysregulated ferritinophagy. RTT fibroblasts exhibited an imbalanced antioxidant defense, particularly after ferroptotic stimuli, and ferroptosis inducers worsened redox imbalance compared to controls. Importantly, a ferroptosis inhibitor (Ferrostatin-1) and a SOD mimetic (mito-TEMPO) prevented these effects and normalized the altered basal conditions of RTT cells. In conclusion, our results reveal a general dysregulation in RTT cells contributing to increased ferroptosis sensitivity. This suggests a significant role for ferroptosis in RTT pathophysiology and progression, potentially opening new therapeutic avenues for this condition.
Lien vers le texte intégral (Open Access ou abonnement)
3. Shu Y, Yang J, Zhang P, Zhang X, Zhao X, Yan J, Zhang B, Du J. Selenium improves behavioral performance in a rat model of autism spectrum disorder by mitigating oxidative stress and modulating the Sirt1/Keap1/Nrf2/HO-1 signaling pathway. Int Immunopharmacol. 2025; 166: 115556.
Autism spectrum disorder (ASD) is a diverse collection of neurodevelopmental disorders often accompanied by excessive oxidative stress and chronic inflammatory responses. Selenium (Se), a trace element, has demonstrated anti-inflammatory, antioxidant, and neuroprotective effects. The present study aimed to examine the effects of sodium selenite, a Se supplement, on a rat model of ASD. The valproic acid intervention method was used during pregnancy to construct an ASD rat model. Rats were then treated with sodium selenite. Behavioral tests, morphological assessments, and measurements of antioxidant enzymes, oxidative stress indicators, and inflammatory factors in the hippocampal tissues and serum were conducted. Se supplementation mitigated inflammatory responses and oxidative stress in ASD rats while preserving neuronal morphology and function. In addition to Se supplementation, rats received specific inhibitors targeting the signaling pathway. Protein and mRNA expression levels, as well as the tissue distribution of sirtuin 1 (Sirt1), heme oxygenase-1 (HO-1), nuclear factor erythroid 2-related factor 2 (Nrf2), and Kelch-like ECH-associated protein 1 (Keap1), were evaluated. The results demonstrated that Se treatment upregulated the expression levels of Sirt1, Nrf2, and HO-1, while downregulating Keap1 expression. These findings demonstrate that Se attenuates inflammatory damage and oxidative stress in the brain, and this protective effect is associated with the Sirt1/Keap1/Nrf2/HO-1 signaling pathway.
