Low Molecular Weight Fucoidan Ameliorates ADHD-like Symptoms in Spontaneously Hypertensive Rats Through Neurochemical and Gut Microbiota Modulation
Attention deficit hyperactivity disorder (ADHD), a prevalent neurodevelopmental disorder characterized by inattention, impulsivity, and hyperactivity, is associated with monoaminergic dysfunction, neuronal damage, and gut microbiota disorders. Low molecular weight fucoidan (LMWF) is a sulfated polysaccharide extracted from Saccharina japonica (Phaeophyta), processes antioxidant, anti-inflammatory, and neuroprotective properties, suggesting its potential relevance for ADHD-related pathophysiology. This study investigated the therapeutic effects of LMWF on ADHD-like symptoms in spontaneously hypertensive rats (SHR). Behavioral tests revealed that LMWF reduced hyperactivity and anxiety-related behavior in the open field test, and improved spatial memory in the Morris water maze test. LMWF treatment significantly increased dopamine (DA), norepinephrine (NE), and 5-hydroxyindoleacetic acid (5-HIAA) levels in the prefrontal cortex (PFC). The transcript levels of tyrosine hydroxylase (Th) and synaptosome-associated protein-25 (Snap25) were upregulated, while dopamine transport (Dat) was downregulated in the PFC. TH protein expression was elevated in the striatum (STR), and neuronal integrity was preserved in the STR and cerebellum. LMWF also reshaped gut microbiota composition and enhanced microbial diversity, contributing to improved gut-brain axis homeostasis. These findings suggest that LMWF may serve as a promising dietary intervention for ADHD through neurochemical restoration and microbiota modulation.