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Updated: Jul 8, 2025
Strategies for Assessing Autistic-Like Behaviors in Mice
Published on: September 20, 2024
Shielding Effect of Ryanodine Receptor Modulator in Rat Model of Autism
Hariom Kumar1, G T Kulkarni1, Vishal Diwan2
1Department of Pharmacology, Amity Institute of Pharmacy, Amity University, Nodia, India.
Insights
Ruthenium red, a ryanodine receptor antagonist, shows neuroprotective effects against propionic acid-induced autism-like symptoms in rats. This compound modulates social behavior, anxiety, and repetitive actions, offering potential therapeutic avenues for autism management.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder characterized by social impairment, communication difficulties, and repetitive behaviors.
- High comorbidity and unclear etiology limit effective therapeutic options, posing a global economic burden.
- Propionic acid (PPA), a gut microbiome metabolite, is implicated in inducing autism-like symptoms in animal models.
Purpose of the Study:
- To investigate the neuroprotective effects of a ryanodine receptor antagonist, Ruthenium red, on propionic acid-induced autism-like behaviors and neurobiological changes in a rat model.
- To assess the modulatory impact of Ruthenium red on anxiety, social behavior, repetitive behaviors, oxidative stress, neuroinflammation, and blood-brain barrier permeability.
Main Methods:
- Autism-like symptoms were induced in male Albino Wistar rats using propionic acid (250 mg/kg) on postnatal days 21-23.
- Rats were treated with Ruthenium red (3 mg/kg) from postnatal day 21 to 50.
- Behavioral assessments (anxiety, social, repetitive behaviors) and neurobiological analyses (oxidative stress markers, inflammatory cytokines, neurotrophic factors, BBB permeability) were performed.
Main Results:
- Ruthenium red significantly countered propionic acid-induced increases in anxiety, repetitive behaviors, and neuroinflammatory markers (IL-6, TNF-α) in the prefrontal cortex.
- It ameliorated oxidative stress (TBARS, GSH levels) and blood-brain barrier disruption (Evans blue leakage, water content).
- Ruthenium red improved social behavior and restored hippocampal CREB and BDNF levels, indicating neurotrophic support.
Conclusions:
- Ryanodine receptor antagonism with Ruthenium red demonstrates significant neuroprotective effects in a propionic acid-induced rat model of autism.
- The findings suggest that targeting ryanodine receptors may offer a novel therapeutic strategy for managing core symptoms of autism.
- Further exploration of ryanodine receptor modulation is warranted for developing effective autism management interventions.
Introduction:
A neurodevelopmental disorder, autism is typically identified with three primary behavioral consequences, such as social impairment, communication problems, and limited or stereotypical behavior. Because of its co-morbidity and lack of therapeutic options, autism is a global economic burden. A short chain of fatty acid, propionic acid is formed biologically by the gut microbiome. Propionic acid levels that are too high can cause leaky intestines, which can lead to autism-like symptoms.
Methods:
To induce autism, male Albino Wistar rats were given propionic acid (250 mg/kg/po on the 21st, 22nd, and 23rd postnatal days). Rats also received a ryanodine receptor antagonist (Ruthenium red: 3 mg/kg/po; postnatal 21st to 50th day) to see what influence it had on propionic acid-induced autism. Anxiety, social behavior, and repeated behaviors were all assessed, as well as oxidative stress, inflammatory indicators, neuro signaling proteins, and blood-brain barrier permeability.
Results:
Ruthenium red was found to counter the propionic acid-induced increases in anxiety, repetitive behavior prefrontal cortex levels of IL-6, TNF-α, TBARS, Evans blue leakage, and water content along with decreases in social behavior, IL-10, and GSH followed by hippocampus CREB and BDNF levels.
Conclusion:
Ryanodine receptor antagonists presented a neuroprotective effect in propionic acid-induced conditions like autism by modulatory effects on social and repetitive behavior, oxidative stress, neuroinflammation, and neuroprotein changes. Ryanodine receptors can be further explored in depth to manage autism as a condition.
Highlights:
Ruthenium red can reduce the propionic acid-induced anxiety of rats with autism.Ruthenium red can improve the propionic acid-induced changes in repetitive behavior of rats with autism.Ruthenium red can reduce the propionic acid-induced social behavior dysfunction in rats with autism.
Plain Language Summary:
Autism is a complex heterogeneous neurodevelopmental disorder mainly diagnosed with social behavior dysfunction, communication problems, and repetitive behavior. Due to high comorbidity and multiple unknown factors involvement, its exact etiology remains unclear, and so no successful treatment is available. Among the environmentally produced models of autism in rats, the most common is created by propionic acid (PPA). With short-chain type fatty acid, PPA is one of the mediators for the cycle of cell metabolism. This study attempted to study the effect of a ryano-dine receptor antagonist (Ruthenium red) on PPA-induced Anxiety, social behavior dysfunction, and repeated behaviors in rats with autism. The results showed the modulatory effects of Ruthenium red PPA-induced conditions including social and repetitive behavior, oxidative stress, neuroinflammation, and neuroprotein changes in rats with autism.
