Recombinant Walnut-Derived Peptide Ameliorates d-Galactose-Induced Cognitive Deficits

Area of Science:

• Neuroscience
• Microbiology
• Immunology

Background:

• Aging and neuroinflammation are linked to gut dysbiosis and systemic inflammation via the gut-brain axis.
• Bioactive peptides, like walnut-derived peptide EV-10, show therapeutic potential for neurodegenerative disorders.
• The therapeutic efficacy of recombinant walnut-derived peptide (rWDP) requires further characterization.

Purpose of the Study:

• To investigate the therapeutic potential of rWDP in a mouse model of aging.
• To elucidate the mechanisms underlying rWDP's effects on cognitive function, gut microbiota, and neuroinflammation.

Main Methods:

• Behavioral assessment using the Morris water maze in d-galactose-induced aging mice.
• Analysis of gut microbiota composition and colon mucosal integrity.
• Measurement of systemic inflammatory markers (IFN-γ, VCAM-1, G-CSF, CXCL1).
• Assessment of microglial activation and neuronal architecture in brain tissue.
• In vitro studies using BV2 microglial cells stimulated with LPS.
• Metabolomic analysis of brain tissue.

Main Results:

• rWDP significantly improved spatial learning and memory in aging mice.
• rWDP treatment altered gut microbiota, increasing Akkermansia muciniphila and improving colon mucosal integrity.
• Systemic inflammation was attenuated, with reduced IFN-γ and VCAM-1, and normalized G-CSF and CXCL1.
• rWDP reduced microglial activation and preserved hippocampal neuronal architecture, with decreased p21 expression in the brain.
• In vitro, rWDP suppressed LPS-induced nitric oxide production and pro-inflammatory gene expression in microglial cells.
• Metabolomic analysis indicated restoration of neurotransmitter homeostasis.

Conclusions:

• rWDP alleviates cognitive deficits in aging mice, potentially through the gut-brain axis and immune modulation.
• rWDP's effects involve beneficial alterations in gut microbiota and reduced neuroinflammation.
• Further research is warranted to fully elucidate the multifaceted mechanisms of rWDP action.