Berberine Alleviates Lipopolysaccharide-Induced Impairments in Neuroplasticity and Spatial Memory by Modulating Microglial Polarization via MAPK Signaling Inhibition

Abstract

Neuroinflammation-induced cognitive impairment is characterized by a continued decline in memory, executive functioning, and information-processing abilities. Although berberine (BBR) exhibits anti-inflammatory and neuroprotective properties, its ability to mitigate cognitive deficits by regulating microglial-mediated neuroinflammation remains incompletely understood. To investigate the potential of BBR in mitigating microglial-mediated neuroinflammation and its detrimental effects on neuroplasticity and spatial memory, a mouse model was established through intrahippocampal microinjection of lipopolysaccharide (LPS). The results showed that BBR pretreatment significantly improved cognitive performance, suppressed microglial activation, reduced hippocampal neuronal damage, and increased the density of functional dendritic spines. Mechanistic analysis revealed that BBR treatment inhibited the phosphorylation of key proteins in the MAPK signaling pathway within microglia. These findings suggest that BBR is a promising therapeutic agent for mitigating neuroinflammation-induced cognitive impairment and provide significant evidence for its potential application in treating inflammation-related cognitive deficits.

Keywords: MAPK signaling; berberine; cognitive impairment; microglia; neuroinflammation.