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

Brain Behav. 2025 Jun;15(6):e70591. doi: 10.1002/brb3.70591.

Abstract

Scope: 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.

Methods and results: 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.

Conclusion: 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.

Keywords: GABA; TLR‐4; autism; behaviors; neuroinflammation; valproic acid.

MeSH terms

  • Animals
  • Autistic Disorder* / chemically induced
  • Autistic Disorder* / diet therapy
  • Autistic Disorder* / metabolism
  • Behavior, Animal* / drug effects
  • Brain / metabolism
  • Disease Models, Animal
  • Functional Food*
  • Mice
  • Myeloid Differentiation Factor 88
  • NF-kappa B / metabolism
  • Polyporaceae* / metabolism
  • Signal Transduction / drug effects
  • Toll-Like Receptor 4
  • Valproic Acid / adverse effects
  • gamma-Aminobutyric Acid* / metabolism

Substances

  • Valproic Acid
  • Tlr4 protein, mouse
  • Myd88 protein, mouse
  • NF-kappa B
  • gamma-Aminobutyric Acid
  • Toll-Like Receptor 4
  • Myeloid Differentiation Factor 88

Supplementary concepts

  • Trametes versicolor