Most cited article - PubMed ID 39461669
Altered sex differences related to food intake, hedonic preference, and FosB/deltaFosB expression within central neural circuit involved in homeostatic and hedonic food intake regulation in Shank3B mouse model of autism spectrum disorder
The increasing incidence of autism spectrum disorder (ASD) increases the urgency of establishing the mechanism of its development for effective prevention and treatment. ASD's etiology includes genetic predisposition and environmental triggers, both of which can play a role in the changed microbiota. Recent research has proved the impact of maternal microbiota on the neurodevelopment of the child. To investigate the co-play of genetic and microbiota factors in ASD development, we performed fecal microbiota transplantation (FMT) from children with ASD to female Shank3b+/- mice and studied the autism-like symptoms in the male Shank3b-/- and wild-type (WT) offspring. WT animals with prenatal exposure to ASD microbiota had delayed neurodevelopment and impaired food intake behavior, but also elevated plasma leptin concentration and body weight. Shank3b-/- mice after FMT ASD exhibited impaired learning and exacerbated anxiety-like behavior in adulthood. Interestingly, FMT ASD improved learning in adolescent Shank3b-/- mice. Prenatal exposure to ASD microbiota decreased the activity of hypocretin neurons of the lateral hypothalamic area in both genotypes. The combination of genetic predisposition and FMT ASD led to an increased colon permeability, evaluated by zonula occludens (ZO1, ZO3) and claudin factors. These results suggest the effect of parental FMT exposure on shaping offspring behavior in Shank3b-/- mice and the potential of microbiota in the modulation of ASD.
- Keywords
- SHANK 3 gene, behavior, fecal microbiota transplantation, maternal microbiota, neurodevelopmental disorder,
- MeSH
- Behavior, Animal MeSH
- Child MeSH
- Fecal Microbiota Transplantation * MeSH
- Humans MeSH
- Disease Models, Animal MeSH
- Mice, Knockout MeSH
- Mice MeSH
- Autism Spectrum Disorder * therapy microbiology genetics MeSH
- Nerve Tissue Proteins * genetics metabolism MeSH
- Gastrointestinal Microbiome MeSH
- Pregnancy MeSH
- Prenatal Exposure Delayed Effects MeSH
- Animals MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Male MeSH
- Mice MeSH
- Pregnancy MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Microfilament Proteins MeSH
- Nerve Tissue Proteins * MeSH
- Shank3 protein, mouse MeSH Browser
