Effects of lifelong sulforaphane intake on behavioural, neurochemical and biomolecular dysfunctions in the BTBR T+ Itpr3tf/J mouse model of autism spectrum disorders.
Abstract
Background
AND
Purpose
Autism spectrum disorders (ASD) are multifactorial neurodevelopmental conditions associated with oxidative stress and neuroinflammation across critical developmental periods. Sulforaphane (SFN), a natural compound with antioxidant and anti-inflammatory properties, is a potential therapeutic strategy for ASD-related alterations. Therefore, we investigated the effects of lifelong SFN exposure on behavioural, neurochemical and biomolecular dysfunctions in BTBR T + Itpr3tf/J (BTBR) male and female mice. EXPERIMENTAL APPROACH Self-Grooming, Marble Burying, Hole Board, Open Field and Social Interaction tests were conducted on C57BL/6 and BTBR male and female mice, fed standard or SFN-enriched diet. Moreover, we quantified cortical levels of neurochemical, redox and neuroinflammatory biomarkers, and plasma proinflammatory cytokines. KEY
Results
Lifelong SFN-enriched diet attenuated stereotyped repertoire, improved exploratory activity and social interactions in both BTBR sexes. SFN decreased cortical serotonergic-, noradrenergic- and kynurenine-pathway-related alterations selectively in BTBR males. SFN supplementation enhanced cortical levels of NRF2, NRF2 DNA-binding activity, haem oxygenase-1 (HO-1) and superoxide dismutase (SOD) 1 in both BTBR sexes, elevated SOD activity in males and glutathione levels in females, reduced reactive oxygen species (ROS) production in males, without affecting NRF2 phosphorylation and kelch-like ECH-associated protein-1 (KEAP1). Furthermore, SFN intake rescued central and peripheral IL-6 and TNF-α levels in BTBR mice of both sexes, while reducing IL-1β and IL-17A levels in males.
Conclusion
AND IMPLICATIONS Our findings suggest that lifelong SFN supplementation ameliorates ASD-like behavioural phenotypes in male and female BTBR mice and reveal sex-specific differences in mitigating biomolecular alterations, thereby pointing towards SFN's potential in sex/gender-personalized preventive and therapeutic approaches.