Dataset Information

Cannabidiol-Induced Recovery of Social Behaviour in Mouse Models of Syndromic Autism

ABSTRACT: Despite the growing prevalence of autism, no pharmacological interventions have been approved for core symptoms. The endocannabinoid system (ECS) has recently gained interest as a potential target for treating autism. Cannabidiol (CBD), a compound found in the Cannabis plant (C. Sativa), is a potential autism treatment due to its tolerability and promising early results in fragile X syndrome patients. Here, we aimed to evaluate the efficacy of CBD in treating social deficits and restrictive/repetitive behaviours in two monogenetic models of autism, Shank3 and Fmr1 knock-out (KO) mice. Male and female mice were tested in the 3-chamber social apparatus or for self-grooming and open field test (baseline or pre-treatment), followed by 5 daily treatments of vehicle or CBD (s.c., 5mg/kg for males, 50mg/kg for females) and tested again after the last injection (post-treatment). At baseline and following vehicle treatment, male and female Shank3 and Fmr1 KO mice exhibited deficits in social novelty, which were restored to control levels following CBD administration. Meanwhile, self-grooming (increased in male and female Shank3 KO mice) and open-field exploration (decreased locomotion in Shank3 KO mice) were not affected by CBD. Females had hippocampal CBD levels ~11.6 times higher than males (concordant with the dosing) and presented elevated levels of anandamide (AEA) in the CBD-treated groups. Transcriptomic analysis of the hippocampus revealed a lack of overlap in the CBD differentially expressed genes (DEGs) among the different strains and between sexes. These results suggest sex- and strain-specific mechanisms for CBD and support its therapeutic effects for syndromic autism.

ORGANISM(S): Mus musculus

PROVIDER: GSE295664 | GEO | 2025/08/31

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Fragile X syndrome and tuberous sclerosis are genetic syndromes that both have a high rate of co-morbidity with autism spectrum disorders. Several lines of evidences suggest that these two monogenic disorders may converge at a molecular level through the dysfunction of activity-dependent synaptic plasticity. We utilized mouse models of these monogenic disorders to identify genome-wide transcriptional changes in cerebellum and blood and characterize the (dis-)similarity of their molecular signatures. Differentially expressed genes and enriched pathways were distinct for the two mouse models examined, with the exception of immune system related pathways. In the cerebellum of the Fmr1 knockout (Fmr1-KO) model, the neuroactive ligand receptor interaction pathway and gene sets associated with synaptic plasticity such as long term potentiation, gap junction, and axon guidance were the most significantly perturbed pathways. The phosphatidylinositol signaling pathway was significantly dysregulated in both blood and brain of Fmr1-KO mice. In both the blood and brain of the Tsc2 heterozygous mouse model, immune system related pathways, genes encoding ribosomal proteins, and glycolipid metabolism pathways were significantly perturbed. Our data suggest that distinct molecular pathways may be involved in autism spectrum disorders with known but different genetic causes, and that blood gene expression profiles of Fmr1-knockout and Tsc2+/- mice mirror some, but not all, of the perturbed molecular pathways in the brain. For the Fmr1-KO model, 10 mice, consisting of 5 KO and 5 WT mice, were profiled. Thus, 10 pairs of blood and cerebella samples were profiled. Likewise, for the Tsc+/- model, 3 transgenic and 3 WT mice were sacrificed and paired blood and cerebella samples were prepared for gene expression profiling. All samples were profiled using the Affymetrix Mouse Gene ST 1.0 ST arrays. Three factors—tissue (i.e. blood vs. cerebellum), treatment (i.e. knockout vs. wildtype), and genetic background (Fmr1-KO vs. Tsc2+/-)—were analyzed with analysis of variance (ANOVA). Subsequently, we compared blood and brain gene expression changes in Fmr1 and Tsc2 knockout mice models using WT littermates as controls using t-tests with unequal variances. The false discovery rate (FDR) was calculated using Storey and Tibshirani’s method.

Dataset Information

Cannabidiol-Induced Recovery of Social Behaviour in Mouse Models of Syndromic Autism

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets