A Novel and Reliable Rat Model of Autism

Abstract

Background: Autism spectrum disorders (ASD) is a complex neurodevelopmental disorder that lacks an ideal animal model to recapitulate the disease state of ASD. Previous studies have reported that transplanting gut microbiota of ASD patients into pregnant mice is sufficient to promote the changes of autism-like behavior in offspring. This study aims to explore whether fecal microbiota transplantation (FMT) can be used as a new method to establish the ASD animal model.Methods: We transplanted the fecal sample extract of ASD children into pregnant rats (rFMT) repeatedly to establish an ASD rat model (oFMT) and compare it with the classical valproic acid (VPA) model (oVPA).Results: First, we reveal that oFMT shows hypoevolutism and typical behavioral characteristics of ASD, consistent with the previous study. Second, the gut microbiota of oFMT mainly consists of Firmicutes and Bacteroidetes, recapitulating the abnormal gut microbiota of ASD. In oFMT, the abundance of Lactobacillus and Collinsella increased (Lactobacillus: oFMT 60.16%, oVPA 64.13%, oCON 40.11%; Collinsella: oFMT 3.73%, oVPA 1.39%, oCON 1.28%), compared with oVPA, gut microbiota also showed high consistency. Third, the expression of 5-hydroxytryptamine (5-HT) in oFMT serum increased, γ-aminobutyric acid (GABA) and norepinephrine (NE) in oFMT serum decreased. Fourth, the gut microbiota of oFMT also has some ASD characteristic gut microbiota not found in oVPA. Fifth, pregnant rat with VPA showed significant immune activation, while those with FMT showed relatively minor immune activation.Limitations: Although the mechanism of establishing FMT autism rat model (oFMT) has not clearly defined, the data show that the model has high structural validity, and FMT model is likely to be a new and reliable potential animal model of ASD, and will have potential value in studying gut microbiota of ASD.Conclusions: The FMT autism rat model has high structural validity, and the FMT model is likely to be a new and reliable potential animal model of ASD.

Pathophysiological Studies of Monoaminergic Neurotransmission Systems in Valproic Acid-Induced Model of Autism Spectrum Disorder

“…In the peripheral system, previous studies have found elevated 5-HT levels in serum, plasma or gastrointestinal tract of VPA-treated rodents, which support the general hyperserotonemia theory of ASD etiology [14,[83][84][85]. However, other studies have reported the reduction in 5-HT-positive cells in the ileum, 5-HT levels and its precursors (tryptophan and 5-HTP), and metabolites (5-HIAA) in both the peripheral system and brain [22,[86][87][88][89].…”

Therapeutic Effects of a Novel Form of Biotin on Propionic Acid-Induced Autistic Features in Rats

“…Various technics/chemicals such as folic acid, thalidomide, valproic acid, propionic acid, and D2 dopamine receptor heterozygous knockout model are used to experimentally induce autistic features in rodents [ 53 , 54 , 55 , 56 , 57 , 58 ]. Numerous studies have proven that the VPA model can be used as an essential tool to examine the underlying mechanism of ASD [ 59 ]. However, this model also has some limitations [ 60 ].…”

Regulation of Neurotransmitters by the Gut Microbiota and Effects on Cognition in Neurological Disorders

“…For example, the transplantation of feces from children with autism induces autism-like behaviors as well as altered tryptophan and serotonin metabolism in germ-free recipient mice [ 103 ]. Another study reports that an autism rat model, transplantation with fecal samples from children with autism results in a decrease in the serum levels of GABA and norepinephrine, an increase in the serum level of serotonin, and increases in the abundance of Lactobacillus and Collinsella [ 104 ]. These results suggest that a typical gut microbial composition from patients with a certain disorder can trigger a disease symptom that is usually accompanied by alterations in neurotransmitter levels.…”