Neuroprotective Effects of Desert Organic Milk Exosomes Against LPS-Induced Cognitive Impairment: Involvement of Microglial M2 Polarization and AMPK Signaling

ABSTRACT: Hippocampal neuroinflammation (HNF) is a key pathological feature in neurodegenerative disorders. Milk-derived exosomes are bioactive extracellular vesicles, yet their potential to regulate neuroinflammatory responses in the brain remains underexplored. This study aimed to characterize the superior properties and protein composition of exosomes derived from desert milk (D-Exo), and to investigate their neuroprotective and anti-neuroinflammatory effects in lipopolysaccharide (LPS)-stimulated BV2 microglial cells and an LPS-induced HNF mice model. Methods: Exosomes were isolated from desert and non-desert milk (ND-Exo). Balb/c mice were orally gavaged with D-Exo or 0.9% NaCl for 28 days before LPS injection. Cognitive function was assessed via behavioral tests, with microglial/astrocyte activation analyzed by immunofluorescence. BV2 microglial cells were pretreated with exosomes prior to LPS stimulation; inflammatory responses and polarization status were examined by RT-PCR. Results: D-Exo showed superior stability and was uniquely enriched with specific proteins (e.g., SIL1, FN1,FGG). These proteins are linked to HNF, blood-brain barrier (BBB) integrity, and the AMPK signaling pathway. In LPS-induced mice, D-Exo administration improved spatial learning and memory, elevated hippocampal brain-derived neurotrophic factor (BDNF) and microtubule-associated protein 2 (MAP2) levels, alleviated cognitive deficits and neuronal damage, and reduced Amyloid-beta 1-42 (Aβ1-42) and Tau accumulation. It also suppressed systemic and neuroinflammatory cytokines while attenuating microgliosis and astrogliosis. In LPS-stimulated BV2 microglia cells, D-Exo shifted microglial polarization from the M1 phenotype toward the M2 phenotype. Conclusions: D-Exo is enriched with specific proteins, attenuates neuroinflammation and cognitive deficits by regulating microglial M1/M2 polarization and AMPK pathway, highlighting its preventive potential.

ORGANISM(S): Bos Taurus

SUBMITTER: Haina Gao  

PROVIDER: PXD071863 | iProX | Thu Dec 11 00:00:00 GMT 2025

REPOSITORIES: iProX