Pubmed du 14/09/25
1. Chatterjee D, Singh S. Neuroprotective effect of ferulic acid in valproic acid induced autism like behaviour in zebrafish via modulation of PI3K/AKT/mTOR pathway. Comp Biochem Physiol C Toxicol Pharmacol. 2025: 110347.
Valproic acid (VPA), a widely used antiepileptic and mood stabilizing drug, is known to induce autism-like features when administered during neurodevelopment. Recent evidence suggests that VPA exposure during adulthood may also elicit autism spectrum disorder (ASD)-like features by altering key signalling pathways, such as phosphoinositide 3-kinase/AKT/mammalian target of rapamycin (PI3K-AKT-mTOR), and cause behavioural and neuromorphological deficits. The study explored the neuroprotective properties of ferulic acid (FA) in VPA-induced cognitive and behavioural impairments. Zebrafish were exposed to VPA at 500 μM for four consecutive days to induce ASD-like features. After 4 days of VPA exposure, they were treated with FA (50, 100, and 200 mg/kg) and risperidone (0.5 mg/kg) for 4 days. Behavioural (T-maze, Novel Tank Driving Test (NTDT), and social interaction), biochemical (oxidative markers), molecular changes (PI3K, mTOR by ELISA, and AKT by immunohistochemistry), and histopathological analyses were performed to confirm the neuroprotective properties of ferulic acid (FA). VPA (500 μM) exposure significantly deteriorated behavioural and molecular alteration levels (p < 0.001 vs. normal control group) in zebrafish. However, FA (100 and 200 mg/kg) significantly improved cognitive and behavioural alterations, as well as oxidative marker and neurotransmitter levels (p < 0.05 vs. VPA group) in zebrafish. Treatment also improved histopathological changes and AKT levels (p < 0.001 vs. the VPA group) in zebrafish. Our results demonstrated that the therapeutic effect of FA in VPA induced autism like symptoms in zebrafish was mediated by its antioxidant, anti-inflammatory, and anti-apoptotic properties through modulation of the PI3K-AKT-mTOR pathway, offering a promising therapeutic strategy for ASD-like symptoms.
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2. 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.
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3. Lila Y, Tseng CJ, Johnston EG, Canales C, McDougle CJ, Hooker JM, Zürcher NR. Choroid plexus alterations in autism spectrum disorder: A PET-MRI study. Brain Behav Immun. 2025; 130: 106110.
The choroid plexus (CP), primarily known as the production site of cerebrospinal fluid (CSF), constitutes one of the sites of the blood-CSF barrier and plays a unique role in inflammation propagation, serving as a key regulator of immune responses. Recent work has shown CP enlargement in neurological and psychiatric disorders with immune involvement. To investigate potential neuroimmune and structural alterations in vivo in autism spectrum disorder (ASD), we assessed the CP-localized expression of mitochondrial translocator protein (TSPO) and CP volume in autistic adults. Sixty-five participants, which included 36 autistic participants and 29 non-autistic controls (CON), completed a simultaneous positron emission tomography-magnetic resonance imaging (PET-MRI) scan with the TSPO radiotracer [(11)C]PBR28. The CP was segmented using subject-level anatomical scans. We observed CP volume enlargement in ASD (mean group difference: 677.8, 95 % CI [331.0, 1025.0], p = 0.0002). In particular, the CP volume of ∼30 % of autistic adults was more than 2 standard deviations above the average CP volume of CON. Exploratory analysis considering sex showed that CP volume was associated with more severe ASD symptoms in autistic males (estimated beta: 153.10, 95 % CI [50.03, 256.30], p = 0.005) and that TSPO in the CP was elevated in autistic females (mean group difference 0.12, 95 % CI [0.03, 0.21], p = 0.01). Our findings reveal volumetric alterations of the human CP in ASD, providing novel insights into the involvement of the CP in ASD.
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4. Lindström R, Kuuluvainen S, Kimppa L, Vainio M, Shtyrov Y, Lepistö-Paisley T, Kujala T. Atypical processing of changes in words and pseudowords in children with autism spectrum disorder. J Commun Disord. 2025; 118: 106563.
OBJECTIVE: The present study explored the neural basis of speech perception in school-aged children with ASD but without language impairments and typically developing control children. METHODS: Event related potentials reflecting stimulus encoding, discrimination, and orientation were recorded to five different speech sound changes (consonant or vowel identity, vowel duration, fundamental frequency, intensity) in carefully matched words and pseudowords. Perceptual discrimination of prosodic changes was assessed with a behavioral test. RESULTS: Impaired speech sound encoding was found for both word and pseudoword stimuli in children with ASD. Reduced neural discrimination of vowel identity changes, consonant changes in pseudowords and vowel duration changes in both words and pseudowords were found in children with ASD. Also, reduced involuntary attention shifting to changes in vowel duration was found in children with ASD. CONCLUSIONS: Results indicate altered speech-sound encoding and reduced cortical discrimination of and orienting to speech-sound changes in complex word-level speech stimuli in school-aged children with ASD but without language impairments. SIGNIFICANCE: The results support the theories suggesting weaknesses in phonemic processing in ASD.