Pubmed du 26/01/25
1. Aller TB, Kelley HH, Juhasz A, Covington B. COVID-19 health distress among autistic adults: Does psychological flexibility explain effects of health distress on mental health concerns?. Autism. 2025: 13623613241313403.
What is already known?In the United States, the COVID-19 Pandemic caused many autistic adults to be fearful and worried about their health. There is a lot of research that says that when autistic adults experience health distress it can worsen their mental health. We do not know, however, what might explain how experiencing health distress negatively affects mental health. Because of this, our participatory action research team wanted to understand if there are strengths-based processes that help us understand the relationship between health distress and mental health concerns.What does this paper add?We examined among 281 autistic adults how a strengths-based construct from acceptance and commitment therapy called psychological flexibility might explain the relationship between health distress and mental health concerns. We found that for adults that had more values progress, doing the things that mattered to them, was associated with better mental health even while experiencing health distress. We also found that values obstruction, getting stuck on uncomfortable thoughts and feelings and trying to avoid them, explained worse mental health for autistic adults experiencing health distress.Implications for research and practice?The findings of this study provide initial support that psychological flexibility can explain the relationship between health distress and mental health concerns among autistic adults. Interventions that seek to improve psychological flexibility, like acceptance and commitment therapy, might be useful in improving autistic adults’ mental health while they are experiencing health distress.
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2. Chen M, Shi J, Liu T, Liu J, Liu Y, Li J, Luo Y, Luo J, Li X, Gong H, Fan X. Astragaloside IV ameliorates autism-like behaviors in BTBR mice by modulating Camk2n2-dependent OXPHOS and neurotransmission in the mPFC. J Adv Res. 2025.
INTRODUCTION: Autism spectrum disorder (ASD) represents a multifaceted set of neurodevelopmental conditions marked by social deficits and repetitive behaviors. Astragaloside IV (ASIV), a natural compound derived from the traditional Chinese herb Astragali Radix, exhibits robust neuroprotective effects. However, whether ASIV can ameliorate behavioral deficits in ASD remains unknown. OBJECTIVES: This work aimed to determine the efficacy and molecular mechanisms of ASIV in ASD. METHODS: The autistic BTBR T + tf/J (BTBR) mice were used in this study. Behavioral tests were performed to assess the ASD-like phenotypes. The neurotransmitter levels and synaptic transmission were evaluated by high-performance liquid chromatography and whole-cell patch-clamp recordings, respectively. Molecular biological techniques, immunostaining, and RNA-sequencing (RNA-seq) were combined to uncover the underlying molecular mechanisms. RESULTS: Our study showed that both social impairment and repetitive behaviors were significantly improved after ASIV treatment in a dose-dependent manner in BTBR mice. The ASIV treatment normalized the neurotransmitter levels (GABA and glutamate) and their corresponding vesicular transporters (vGAT, vGLUT1) in the medial prefrontal cortex (mPFC). Furthermore, the excitation-inhibition imbalance in layer V of mPFC was reversed after ASIV administration. Mechanistically, bulk RNA-seq and PPI network analysis identified Camk2n2 as the crucial bridging gene regulating oxidative phosphorylation and neurotransmission. Camk2n2 overexpression in the mPFC abolished the beneficial effects of ASIV on autistic symptoms in BTBR mice via the Camk2/CREB pathway. CONCLUSION: The evidence demonstrates that ASIV may become a promising treatment option for ASD and implies that targeting the Camk2n2/Camk2/CREB axis is warranted to investigate these ASD individuals further.
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3. Lee SM, Choi Y, Kim D, Jeong HJ, Do YH, Jung S, Lee B, Choi HJ, Kim S, Oh JM, Jeon S, Han J, Kim Y. Developmental deficits, synapse and dendritic abnormalities in a Clcn4 KO autism mice model: endophenotypic target for ASD. Transl Psychiatry. 2025; 15(1): 28.
Autism spectrum disorder (ASD) is linked to ion channel dysfunction, including chloride voltage-gated channel-4 (CLCN4). We generated Clcn4 knockout (KO) mice by deleting exon 5 of chromosome 7 in the C57BL/6 mice. Clcn4 KO exhibited reduced social interaction and increased repetitive behaviors assessed using three-chamber and marble burying tests. Surprisingly, these symptoms were improved by Risperidone treatment, a drug commonly used to treat ASD. RNA sequencing data from mouse neural progenitor cells (mNPCs) showed that the genes regulating trans-synaptic signaling, transmembrane transport, and neuronal projection development were significantly decreased in Clcn4 knockdown (KD) cells compared to wild type (WT). Moreover, Risperidone treatment increased the genes related to the ion transmembrane transport, membrane potential, and neuron projection development in Clcn4 KD. Abnormalities in synaptic plasticity and dendritic spine formation were also observed in Clcn4 KO compared to WT. We observed that phosphorylation of SYNAPSIN, PSD95, ERK and CREB, as well as the expression of CDK5, were reduced in the brains of Clcn4 KO mice. In Clcn4 KO cortical neurons, the phosphorylation of SYNAPSIN and PSD95 expressions also decreased compared to WT, indicating disrupted synaptic function. Additionally, Sholl analysis revealed a reduction in dendritic branching and neuronal projection length in both mouse and human CLCN4 KD neurons. Finally, the decreased phosphorylation of SYNAPSIN and expression of PSD95 along with dendrite abnormalities were restored after Risperidone treatment. These data suggest that dendritic outgrowth and synapse remodeling may serve as endophenotypic targets for drug efficacy in ASD.
