Atractylodes macrocephala polysaccharide AMP1-1 ameliorates weightless-induced cognitive dysfunction via the...

Area of Science:

• Neuroscience
• Microbiology
• Pharmacology

Background:

• Atractylodes macrocephala Koidz. (AMP1-1) exhibits gastrointestinal and immunomodulatory effects.
• The gut-brain axis plays a crucial role in cognitive function.
• Weightlessness can induce cognitive impairment, potentially mediated by the gut-brain axis.

Purpose of the Study:

• To investigate the protective effect of AMP1-1 against weightlessness-induced cognitive impairment.
• To elucidate the underlying mechanism involving the microbiota-gut-brain axis.

Main Methods:

• A tail-suspension rat model simulated weightlessness.
• Cognitive function was assessed using behavioral tests.
• Neuroinflammation, barrier integrity, and gut microbiota were analyzed using histological staining, ELISA, Western blot, 16S rDNA sequencing, and metabolomics.
• Fecal microbiota transplantation (FMT) and butyrate supplementation were used for mechanistic validation.

Main Results:

• AMP1-1 administration improved cognitive performance and enhanced intestinal and blood-brain barrier integrity.
• AMP1-1 inhibited hippocampal neuroinflammation via the TLR4/MyD88/NF-κB pathway.
• AMP1-1 modulated gut microbiota composition, increased fecal butyrate, and reduced lipopolysaccharide (LPS).
• FMT and butyrate supplementation replicated AMP1-1's protective effects.

Conclusions:

• AMP1-1 alleviates weightlessness-induced cognitive impairment by promoting gut microbiota-derived butyrate production.
• This mechanism involves restoring gut and brain barriers, suppressing inflammation, and inhibiting the hippocampal TLR4/MyD88/NF-κB pathway.
• AMP1-1 shows promise as a prebiotic agent for preventing neuroinflammation-related cognitive decline in microgravity.