Work

β-glucan-loaded nano-niosomes ameliorate spatial and associative memory impairment in a D-galactose-induced aging rat model via modulation of microglial pyroptosis and autophagy

Year: 2025

Type: article

Abstract: INTRODUCTION: Considering the anti-inflammatory effects of β-glucan, a natural polysaccharide, this study investigated whether β-glucan nano-formulated in niosomes (vesicles made of non-ionic surfactants used for drug delivery) could improve spatial and associative memories in a D-galactose-induced aging rat model by modulating neuroinflammation, microglial autophagy (cellular recycling by microglia), and pyroptosis (inflammatory programmed cell death). METHODS: Sixty Wistar rats were randomly divided into six groups (n = 10 pre group). An aging model was induced in relevant groups via chronic D-galactose injection (180 mg/kg, i.p.) for 8 weeks. Anti-inflammatory effects of orally administered β-glucan (8 mg/kg) encapsulated in nano-niosomes were evaluated. Behavioral performance was assessed using the Y-maze (spatial working memory), passive avoidance (associative and long-term memory), and Barnes maze tests (spatial learning and reference memory). Oxidative stress was measured via reactive oxygen species (ROS) levels. Western blot assessed autophagy-related proteins in the PI3K/AKT/mTOR (a negative regulator of autophagy) pathway. Immunofluorescence examined Iba1 (microglial activation), LC3-II (autophagy), CD86 (pro-inflammatory microglia), and NLRP3 inflammasome (a key mediator of inflammatory cell death) components. Hippocampal pro-inflammatory cytokines were quantified by ELISA. RESULTS: D-galactose impaired spatial and associative memory, increased ROS, disrupted PI3K/AKT/mTOR autophagy signaling, reduced LC3-II, elevated CD86, triggered microglial pyroptosis, and caused neuroinflammation. Nano-formulated β-glucan reversed these effects, improving spatial and associative memories, reducing ROS, restoring autophagy, suppressing CD86 and pyroptosis, and attenuating neuroinflammation. CONCLUSIONS: β-glucan-loaded nano-niosomes exert neuroprotective effects through the simultaneous modulation of autophagy dysfunction and microglial-mediated inflammation, highlighting its potential as a therapeutic agent for neurodegenerative conditions. However, translation to human clinical practice remains uncertain and should be addressed in future studies using human-relevant models and early-phase clinical trials.

Source: Biomedicine & Pharmacotherapy

DOI: 10.1016/j.biopha.2025.118834

Authors: Fatemeh Rahmati-Dehkordi, Elham Zahedi, Soheila Adeli, Hamidreza Sahrayi, Seyed Morteza Karimian

Institutions: Tehran University of Medical Sciences, Iran University of Medical Sciences, Sharif University of Technology

Language: English

Topic: Neuroinflammation and Neurodegeneration Mechanisms

Subfield: Neurology

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,610