Polysaccharides from Polygonatum cyrtonema Hua prevent post-traumatic stress disorder behaviors in mice: Mechanisms from the perspective of synaptic injury, oxidative stress, and neuroinflammation

To investigate the preventive effect of PSP on PTSD-like behaviors and to determine the mechanisms.

PSP prevents SPS-induced PTSD-like behaviors and synaptic damage by regulating oxidative stress and NLRP3-mediated inflammation, probably in an Nrf2/HO-1 signaling pathway-dependent manner.

We used behavioral tests to evaluate PTSD-like behaviors in mice. Synaptic changes were assessed by transmission electron microscopy. Hematoxylin-eosin staining was used to assess pathological changes to the hippocampus, and immunofluorescence staining was used to observe changes in astrocytes. Serum corticosterone (CORT), cytokine, and hippocampal oxidation-related indicator levels were evaluated by ELISA. We detected the expression levels of synaptic, oxidative, and inflammation-related proteins in the hippocampus by western blotting.

Single prolonged stress (SPS)-modeled mice exhibited significant PTSD-like phenotypes, including increased fear memory acquisition and anxiety-like behaviors. These behavioral changes were prevented by PSP administration. Compared to controls, SPS modeling increased serum CORT, cytokine, and hippocampal malondialdehyde levels; decreased superoxide dismutase activity; and caused losses in pyramidal neurons, astrocytes, and synapses in the CA1 region. At the molecular level, the expression of brain-derived neurotrophic factor, postsynaptic density protein 95, nuclear factor erythroid 2-related factor 2 (Nrf2), phospho-tyrosine kinase receptor B, activity-regulated cytoskeleton-associated protein, heme oxygenase-1 (HO-1), and GluA1 decreased in SPS mice compared with the control group, while the expression of NOD-like receptor protein 3 (NLRP3), GluN2B, and apoptosis-associated speck-like protein increased in SPS mice. Treatment with PSP counteracted these abnormal changes. Importantly, ML385, an Nrf2 inhibitor, blocked PSP's ability to ameliorate PTSD behaviors and abnormal protein expression. The NLRP3 inhibitor MCC950 reduced the PTSD-like behaviors and normalized protein expression in SPS mice.