Retinoic Acid Supplementation Rescues the Social Deficits in Fmr1 Knockout Mice

Abstract

Autism spectrum disorder (ASD) is a heritable neurodevelopmental disorder with the underlying etiology yet incompletely understood and no cure treatment. Patients of fragile X syndrome (FXS) also manifest symptoms, e.g. deficits in social behaviors, that are core traits with ASD. Several studies demonstrated that a mutual defect in retinoic acid (RA) signaling was observed in FXS and ASD. However, it is still unknown whether RA replenishment could pose a positive effect on autistic-like behaviors in FXS. Herein, we found that RA signaling was indeed down-regulated when the expression of FMR1 was impaired in SH-SY5Y cells. Furthermore, RA supplementation rescued the atypical social novelty behavior, but failed to alleviate the defects in sociability behavior or hyperactivity, in Fmr1 knock-out (KO) mouse model. The repetitive behavior and motor coordination appeared to be normal. The RNA sequencing results of the prefrontal cortex in Fmr1 KO mice indicated that deregulated expression of Foxp2, Tnfsf10, Lepr and other neuronal genes was restored to normal after RA treatment. Gene ontology terms of metabolic processes, extracellular matrix organization and behavioral pathways were enriched. Our findings provided a potential therapeutic intervention for social novelty defects in FXS.

Pharmacotherapeutic effects of cannabidiol in autism spectrum disorders

“…Regardless of the treatment, this difference is no longer present in the second test, suggesting that this mild deficit in the sociability index can be restored by repeated exposure to a novel social stimulus. These findings highlight that Fmr1 KO mice do not have a sociability deficiency, consistent with existing literature (Yang et al, 2022). The same is true for Shank3 KO mice, who have been documented to prefer a social target over an inanimate object when subjected to this test (Jaramillo et al, 2017).…”

Novel insights into the immune cell landscape and gene signatures in autism spectrum disorder by bioinformatics and clinical analysis

“…We further found identified agents-gene axes using the DSigDB database. The existing studies have shown different types of agents affecting ASD, including those that improve ASD (resveratrol, vitinoin, vitamin E, and retinoic acid) ( 78 – 82 ) and those that exacerbate ASD (valproic acid, arsenic, benzo[a]pyrene, and acetaminophen) ( 83 – 86 ). Moreover, there are ASD-related agents with unknown risks, including reagents with neurotoxicity and immunotoxicity (platinum, bortezomib, tert-butyl hydroperoxide, vincristine, atrazine, 7646-79-9, hydrogen peroxide, aflatoxin B1, and copper sulfate) ( 87 – 95 ) or agents providing neuroprotection and immune regulation (genistein, cyclosporin A, and decitabine) ( 96 – 98 ) and agents that require exploration in terms of immune and neurological function (hematoxylin and tetradioxin).…”

Is Autism a PIN1 Deficiency Syndrome? A Proposed Etiological Role for Glyphosate

“…In a study published in 2018, vitamin A deficiency was found in 78% of autistic children, and vitamin A supplementation improved autistic symptoms [27]. In a genetic mouse model of autism, retinoic acid treatment rescued social deficits [28]. In a valproateinduced mouse model of autism, prenatal exposure to ascorbate attenuated the effects of valproate on the autistic behaviors of the pups [29].…”