Dataset Information

Acid-Responsive Dual-Targeted Nanoparticles Encapsulated Aspirin Rescue the Immune Activation and Phenotype in Autism Spectrum Disorder.

ABSTRACT: The treatment of autism spectrum disorder (ASD) is one of the most difficult challenges in neurodevelopmental diseases, because of the unclear pathogenesis research and low brain-lesion targeting efficiency. Besides, maternal immune activation has been reported as the most mature and widely used model of ASD and aspirin-triggered lipoxin A4 is a potent anti-inflammatory mediator being involved in the resolution of neuroinflammation in ASD. Therefore, an aspirin encapsulated cascade drug delivery system (Asp@TMNPs) is established, which can successively target the blood-brain barrier (BBB) and microglial cells and response to the acid microenvironment in lysosome. As a result, the mitochondrial oxidative stress, DNA damage, and inflammation of microglial cells are prominently alleviated. After the treatment of Asp@TMNPs, the social interaction, stereotype behavior, and anxious condition of ASD mice are notably improved and the activation of microglial cells is inhibited. Overall, this system successively penetrates the BBB and targets microglial cells, therefore, it significantly enhances the intracephalic drug accumulation and improves anti-neuroinflammatory efficacy of aspirin, providing a promising strategy for ASD treatment.

SUBMITTER: He X

PROVIDER: S-EPMC9108608 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Acid-Responsive Dual-Targeted Nanoparticles Encapsulated Aspirin Rescue the Immune Activation and Phenotype in Autism Spectrum Disorder.

He Xueqin X Xie Jiang J Zhang Jing J Wang Xiaorong X Jia Xufeng X Yin Heng H Qiu Zhongqing Z Yang Zhihang Z Chen Jiao J Ji Zhiliang Z Yu Wenqi W Chen Meiwan M Xu Wenming W Gao Huile H

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20220313 14

The treatment of autism spectrum disorder (ASD) is one of the most difficult challenges in neurodevelopmental diseases, because of the unclear pathogenesis research and low brain-lesion targeting efficiency. Besides, maternal immune activation has been reported as the most mature and widely used model of ASD and aspirin-triggered lipoxin A4 is a potent anti-inflammatory mediator being involved in the resolution of neuroinflammation in ASD. Therefore, an aspirin encapsulated cascade drug delivery ...[more]

PMID: 35285177

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Project description:Pathogenic disruptions to the activity-dependent neuroprotector homeobox (ADNP) gene are among the most common heterozygous genetic mutations associated with autism spectrum disorders (ASDs). Individuals with ADNP disruptions share a constellation of medical and psychiatric features, including ASD, intellectual disability (ID), dysmorphic features, and hypotonia. However, the profile of ASD symptoms associated with ADNP may differ from that of individuals with another ASD-associated single gene disruption or with ASD without a known genetic cause. The current study examined the ASD phenotype in a sample of representative youth with ADNP disruptions. Participants (N = 116, ages 4-22 years) included a cohort with ADNP mutations (n = 11) and three comparison groups with either a mutation to CHD8 (n = 11), a mutation to another ASD-associated gene (other mutation; n = 53), or ASD with no known genetic etiology (idiopathic ASD; n = 41). As expected, individuals with ADNP disruptions had higher rates of ID but less severe social affect symptoms compared to the CHD8 and Idiopathic ASD groups. In addition, verbal intelligence explained more variance in social impairment in the ADNP group compared to CHD8, other mutation, and idiopathic ASD comparison groups. Restricted and repetitive behaviors in the ADNP group were characterized by high levels of stereotyped motor behaviors, whereas the idiopathic ASD group showed high levels of restricted interests. Taken together, these results underscore the role of ADNP in cognitive functioning and suggest that social impairments in ADNP syndrome are consistent with severity of verbal deficits. Autism Res 2018, 11: 1300-1310. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Disruptions to the ADNP gene (i.e., ADNP syndrome) have been associated with autism spectrum disorder (ASD). This article describes intellectual disability, mild social difficulties, and severe repetitive motor movements in a group of 11 youth with ADNP Syndrome. We found lower rates of ASD than previously reported. Verbal skills explained individual variability in social impairment. This pattern suggests that the ADNP gene is primarily associated with learning and memory, and level of social difficulties is consistent with level of verbal impairment.

Dataset Information

Acid-Responsive Dual-Targeted Nanoparticles Encapsulated Aspirin Rescue the Immune Activation and Phenotype in Autism Spectrum Disorder.

Publications

Acid-Responsive Dual-Targeted Nanoparticles Encapsulated Aspirin Rescue the Immune Activation and Phenotype in Autism Spectrum Disorder.

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