Protection of <i>Tricholoma matsutake</i> and Its Bioactive Components against Cognitive Impairment: Modulating Oxidative Stress, Alleviating Neuroinflammation, and Preserving Synaptic Plasticity

The rising incidence of neuroinflammation in modern society has garnered significant attention. Current research primarily focuses on dietary supplementation with edible fungi to mitigate cognitive impairment, but there is still a big gap. This study investigated the effects of <i>Tricholoma matsutake</i> powder (TP) and its primary bioactive components, proteins (TPT) and polysaccharides (TPS), on memory function in LPS-induced neuroinflammatory mice and also preliminarily explored the underlying mechanisms. The results indicate that daily oral administration of TPT reversed cognitive and memory impairment caused by LPS in mice, alleviated Nissl body reduction, increased cholinergic system activity, and modulated oxidative stress. Furthermore, TPT mitigated the increase of intestinal permeability in LPS-induced mice, thereby modulating inflammation progression and its transmission to the hippocampus. It also enhances synaptic plasticity by regulating microglial and astrocyte activation. The protective mechanism of TPT on synaptic plasticity involves increasing dendritic spine density, particularly enhancing the proportion of mushroom spines, and mitigating synaptic ultrastructural damage. These findings suggest that <i>T. matsutake</i> mitigates memory impairment and that the relative amount of protein plays a more prominent prophylactic role. This provides valuable insights for developing nutritional products to prevent neurodegenerative diseases.