Abstract
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
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(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.