Trigonelline attenuates valproic acid-induced autism-like behaviours in rats: histopathological changes of the hippocampus, modulation of gene expressions related to neuroinflammation and blood-brain barrier permeability.
TL;DR
Investigation of Trigonelline's effects on autistic phenotype, gene expression of tight junction proteins associated with BBB integrity, neuroinflammation and histopathological changes in the hippocampus in valproic acid - induced autism in rats found it significantly attenuated autistic behaviors.
Abstract
Background
Autism spectrum disorders (ASD) is a neurodevelopmental disorder. Neuroinflammation and bloodbrain barrier (BBB) dysfunction have role in the pathophysiology of ASD. Trigonelline (TRI) exerted neuroprotective effects. We aimed to investigate TRI's effects on autistic phenotype, gene expression of tight junction proteins associated with BBB integrity, neuroinflammation and histopathological changes in the hippocampus in valproic acid (VPA) - induced autism in rats.
Methods
Pregnant Wistar rats received single subcutaneous injection of VPA (600mg/kg) on day 12 of gestation. Animals were treated with normal saline or TRI for one week. Repetitive behaviours, anxiety-like behaviour, memory function, and social interactions were assessed. The thickness and dark neurons of the CA1 and CA3 regions of hippocampus were examined. The inflammatory genes, including Tlr4, Tnf-α, and Il-1β, along with claudins (Cldn -3, Cldn-5, and Cldn-12), were measured in the hippocampus.
Results
TRI significantly attenuated autistic behaviors. TRI reduced the expression of inflammatory markers and modulated the expression of claudins. TRI increased the thickness and decreased the number of dark neurons in the CA1 and CA3 regions.
Conclusions
TRI reduced autistic behaviours probably through attenuation of neuroinflammation, preservation of the hippocampus, and modulation of gene expressions of tight junction proteins associated with the BBB permeability.