# ⁠⁠Functional Foods Alleviate Behavioral Alterations and Improve GABAergic System Regulating TLR‐4/NF‐κB Axis in Valproic‐Induced Autism

**Authors:** Francesco Molinari, Roberta Fusco, Rosalba Siracusa, Ramona D'Amico, Daniela Impellizzeri, Ali S. Abdelhameed, Tilman Fritsch, Ursula M. Jacob, Salvatore Cuzzocrea, Vittorio Calabrese, Rosanna Di Paola, Marika Cordaro

PMC · DOI: 10.1002/brb3.70591 · Brain and Behavior · 2025-06-04

## TL;DR

Functional foods like Coriolus versicolor reduce autism-like behaviors in mice by improving brain inflammation and GABA levels.

## Contribution

This study shows Coriolus versicolor mitigates VPA-induced autism symptoms via the TLR-4/NF-κB pathway and GABAergic system.

## Key findings

- CV reduced behavioral impairments and self-harming behaviors in VPA-exposed mice.
- CV reversed cerebellar and hippocampal disorganization caused by VPA.
- CV improved neuroinflammation by modulating the TLR-4/Myd88/NF-κB signaling pathway.

## Abstract

Valproic acid (VPA) postnatal exposure in mice results in behavioral impairment, aberrant sensitivity to sensory stimuli, and self‐harming behavior, hallmarks of autism. According to previous reports, Coriolus versicolor (CV) has a protective effect on the brain. The goal of the current investigation was to assess how CV affected the neurobehavioral and metabolic changes caused by VPA in mice.

Mice pups were injected with VPA at 14 days of age and orally administered CV at a dose of 200 mg/kg daily from 14 to 40 days of age. Mice pups were placed through behavioral tests during the trial to evaluate motor skill growth, nociceptive response, locomotion, anxiety, and cognition. Following behavioral testing, mice were killed, and the brain was removed and subjected to biochemical analyses (glutathione, malondialdehyde, and nitric oxide) and histopathological analysis. Additionally, to further investigate the role of the TLR‐4/Myd88/NF‐κB signaling pathway, we examined the modulation of this pathway and the alteration in gamma‐amino butyric acid (GABA) production using Western blot analysis.

According to our research, CV daily administration greatly reduced behavioral alteration, reversed the disorganization of the cerebellum and hippocampus, and significantly improved the VPA‐induced neuroinflammation via the TLR‐4/Myd88/NF‐κB signaling cascade.

Dietary supplementation with Coriolus versicolor ameliorate neuroinflammation VPA‐induced.

## Linked entities

- **Proteins:** TLR4 (toll like receptor 4), NFKB1 (nuclear factor kappa B subunit 1), MYD88 (MYD88 innate immune signal transduction adaptor), GABA-B-R1 (metabotropic GABA-B receptor subtype 1)
- **Chemicals:** Valproic acid (PubChem CID 3121), glutathione (PubChem CID 124886), malondialdehyde (PubChem CID 10964), nitric oxide (PubChem CID 145068)
- **Diseases:** autism (MONDO:0005260)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Diseases:** Autism (MESH:D001321), neuroinflammation (MESH:D000090862), anxiety (MESH:D001007), behavioral impairment (MESH:D001523)
- **Chemicals:** nitric oxide (MESH:D009569), VPA (MESH:D014635), malondialdehyde (MESH:D008315), Valproic (-), GABA (MESH:D005680), glutathione (MESH:D005978)
- **Species:** Mus musculus (house mouse, species) [taxon 10090]

## Full text

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## Figures

9 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12134490/full.md

## References

105 references — full list in the complete paper: https://tomesphere.com/paper/PMC12134490/full.md

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Source: https://tomesphere.com/paper/PMC12134490