Inhibition of Striatal miR-141-3p Ameliorates Cognitive Deficits and Neuroinflammation in an ADHD Animal Model

Background/Objectives: Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder characterized by inattention, hyperactivity, and impulsivity that may persist into adulthood. Emerging evidence suggests that microRNAs (miRNAs) contribute to ADHD pathogenesis, but the role of miR-141-3p remains unclear. This study investigated the effects of miR-141-3p inhibition on ADHD-like behaviors in spontaneous hypertensive rats (SHRs). Methods: We used RT-qPCR, immunoblotting, immunohistochemistry, ELISA, and a Y-maze test to assess molecular and behavioral changes after striatal stereotaxic injection of an miR-141-3p antagomir (AT). Results: Striatal miR-141-3p expression was significantly higher in SHRs than in WKY rats, while taurine treatment reduced its expression. Inhibition of miR-141-3p suppressed inflammasome-related signaling pathways, including the TLR4/NF-κB/NLRP3 and TNF-α/NF-κB/NLRP3 pathways. It also reduced the number of NLRP3-positive cells and the levels of IL-1β, IL-18, and IL-17A in the striatum and improved spontaneous alternation performance in the Y-maze. Conclusions: These findings suggest that miR-141-3p may contribute to ADHD-like pathology through neuroinflammatory mechanisms and warrants further investigation as a potential therapeutic target.