Retinoic Acid Supplementation Rescues the Social Deficits in Fmr1 Knockout Mice

Yang, Long; Xia, Zhongfang; Feng, Jianhua; Zhang, Menghuan; Miao, Pu; Nie, Yingjie; Zhang, Xiangyan; Hao, Zijian; Hu, Ronggui

doi:10.3389/fgene.2022.928393

Cited by 6 publications

(4 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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).…”

Section: Male Sociability Is Not Affected In Fmr1 and Shank3 Ko Micesupporting

confidence: 91%

Pharmacotherapeutic effects of cannabidiol in autism spectrum disorders

Parkhill

View full text Add to dashboard Cite

Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders characterized by social deficits and restrictive/repetitive behaviour. ASD is diagnosed in roughly 1-2% of the global population. Despite the prevalence of ASD, very few pharmaceutical interventions have been approved for its treatment. The endocannabinoid system (ECS) has recently gained interest as a potential target for treating ASD. Cannabidiol (CBD), a compound found in the Cannabis (C. Sativa) plant, has been highlighted as a potential drug through which the ECS can be mediated. Due to its non-psychoactive nature, and its efficacy in ameliorating ASD-associated symptoms in Fragile X syndrome (FXS) patients, an investigation into its effectiveness in treating ASD is warranted. In this present thesis, we aimed to evaluate the efficacy of CBD in treating social deficits and restrictive/repetitive behaviours in Fmr1 and Shank3 knockout mice. These models serve as two well-characterized monogenetic animal models of ASD. To account for a knowledge gap in the literature surrounding the treatment of ASD, both male and female mice were used. Mice were assigned to the 3-chamber social test, or self-grooming and open field tests. Mice received subcutaneous injections of either vehicle or CBD (5mg/kg for males, 50mg/kg for females). On the first day, mice performed their respective tests to establish a baseline for behaviour. For the 4 following days, mice received 1 injection daily. On the 6 th day, mice were given another injection. An hour later, they were subjected to their post-injection behavioural testing. Results from the 3-chamber social test showed that both knockout models displayed deficits in social novelty. This deficit was recovered following the administration of CBD. Self-grooming analysis and open-field testing showed no effect of CBD.These findings suggest CBD exerts its therapeutic effects through regions specific to social memory, likely the CA1 and CA2 regions of the hippocampus.

show abstract

Section: Male Sociability Is Not Affected In Fmr1 and Shank3 Ko Micesupporting

confidence: 91%

Pharmacotherapeutic effects of cannabidiol in autism spectrum disorders

Parkhill

View full text Add to dashboard Cite

show abstract

“…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).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2023

Front. Immunol.

View full text Add to dashboard Cite

The pathogenesis of autism spectrum disorder (ASD) is not well understood, especially in terms of immunity and inflammation, and there are currently no early diagnostic or treatment methods. In this study, we obtained six existing Gene Expression Omnibus transcriptome datasets from the blood of ASD patients. We performed functional enrichment analysis, PPI analysis, CIBERSORT algorithm, and Spearman correlation analysis, with a focus on expression profiling in hub genes and immune cells. We validated that monocytes and nonclassical monocytes were upregulated in the ASD group using peripheral blood (30 children with ASD and 30 age and sex-matched typically developing children) using flow cytometry. The receiver operating characteristic curves (PSMC4 and ALAS2) and analysis stratified by ASD severity (LIlRB1 and CD69) showed that they had predictive value using the “training” and verification groups. Three immune cell types – monocytes, M2 macrophages, and activated dendritic cells – had different degrees of correlation with 15 identified hub genes. In addition, we analyzed the miRNA-mRNA network and agents-gene interactions using miRNA databases (starBase and miRDB) and the DSigDB database. Two miRNAs (miR-342-3p and miR-1321) and 23 agents were linked with ASD. These findings suggest that dysregulation of the immune system may contribute to ASD development, especially dysregulation of monocytes and monocyte-derived cells. ASD-related hub genes may serve as potential predictors for ASD, and the potential ASD-related miRNAs and agents identified here may open up new strategies for the prevention and treatment of ASD.

show abstract

“…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].…”

Section: Introductionmentioning

confidence: 99%

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

Seneff,

Kyriakopoulos,

Nigh

2024

Preprint

View full text Add to dashboard Cite

Autism is a neurodevelopmental disorder whose prevalence has increased dramatically in the United States over the past two decades. It is characterized by stereotyped behaviors and impairments in social interaction and communication. In this paper, we present evidence that autism can be viewed as a PIN1 deficiency syndrome. PIN1 (Peptidylprolyl Cis/Trans Isomerase, NIMA-Interacting 1) is a peptidylprolyl cis/trans isomerase, and it has widespread influences in biological organisms. Broadly speaking, PIN1 deficiency is linked to many neurodegenerative diseases, whereas PIN1 overexpression is linked to cancer. Death associated protein kinase 1 (DAPK1) strongly inhibits PIN1, and the hormone melatonin inhibits DAPK1. Melatonin deficiency is strongly linked to autism. It has recently been shown that glyphosate exposure to rats inhibits melatonin synthesis due to increased glutamate release from glial cells and increased expression of metabotropic glutamate receptors. Glyphosate's inhibition of melatonin leads to a reduction in PIN1 availability in neurons. In this paper, we show that PIN1 deficiency can explain many of the unique morphological features of autism, including increased dendritic spine density, missing or thin corpus callosum and reduced bone density. We show how PIN1 deficiency disrupts the functioning of powerful high level signaling molecules, such as nuclear factor erythroid 2-related factor 2 (NRF2) and p53. Dysregulation of both of these proteins has been linked to autism. Severe depletion of glutathione in the brain resulting from chronic exposure to oxidative stressors and extracellular glutamate leads to oxidation of the cysteine residue in PIN1, inactivating the protein and further contributing to PIN1 deficiency. Impaired autophagy leads to increased sensitivity of neurons to ferroptosis. Finally, we consider evidence of the potential toxic effects of the mRNA SARS-CoV-2 vaccines in the light of metabolic defects in autism, and we propose that children with autism would be especially sensitive to damage from the vaccines.

show abstract

Retinoic Acid Supplementation Rescues the Social Deficits in Fmr1 Knockout Mice

Cited by 6 publications

References 63 publications

Pharmacotherapeutic effects of cannabidiol in autism spectrum disorders

Pharmacotherapeutic effects of cannabidiol in autism spectrum disorders

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

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

Contact Info

Product

Resources

About