High-amylose diet ameliorates LPS-induced cognitive impairment and depression-like phenotype

Neurosci Lett. 2025 Jul 27:862:138295. doi: 10.1016/j.neulet.2025.138295. Epub 2025 Jun 9.

Abstract

Neuroinflammation is accompanied by the activation of glial cells, such as microglia and astrocytes. The cytokines released by these glial cells affect neurons, causing their dysfunction and eventually leading to cell death. Neuroinflammation has been suggested to cause cognitive function decline as well as psychiatric disorders, such as major depressive disorders (MDD). In recent years, from the perspective of the gut-brain axis, a prebiotic approach has been considered to improve neuroinflammation. The ingestion of resistant starch has been reported to increase the number of short-chain fatty acid (SCFA)-producing bacteria, and SCFA may suppress neuroinflammation through the gut-brain relationship in both humans and rodents. It is reported that diets rich in amylose, a type of resistant starch, lead to an increase in SCFA levels in the feces of mice. Based on these findings, we hypothesized that a high-amylose diet can ameliorate cognitive impairment and depression-like behaviors driven by neuroinflammation. In the present study, we employed lipopolysaccharides (LPS) to induce neuroinflammation in mice. A fear conditioning test showed that this prebiotic method suppressed the decline of associative learning caused by LPS. In addition, tail suspension and forced swim tests showed the ameliorating effect of this prebiotic method on LPS-induced depression-like behaviors. These results suggest that resistant starch has a prebiotic effect, improving cognitive function decline and depression-like symptoms caused by LPS.

MeSH terms

  • Amylose* / administration & dosage
  • Animals
  • Cognitive Dysfunction* / chemically induced
  • Cognitive Dysfunction* / diet therapy
  • Depression* / chemically induced
  • Depression* / diet therapy
  • Lipopolysaccharides / toxicity
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neuroinflammatory Diseases / chemically induced
  • Neuroinflammatory Diseases / diet therapy
  • Phenotype
  • Prebiotics / administration & dosage

Substances

  • Lipopolysaccharides
  • Amylose
  • Prebiotics