Abstract
This study investigates the therapeutic effectiveness of intranasal dantrolene nanoparticles pretreatment to inhibit lipopolysaccharide (LPS)-induced pathological inflammation and synapse destruction and depressive and anxiety behavior in mice. B6SJLF1/J adult mice were pretreated with intranasal dantrolene nanoparticles (dantrolene: 5mg/kg), daily, Monday to Friday, 5 days per week, for 4 weeks. Then, mice were treated with intraperitoneal injection of LPS (5mg/kg) for one time. Behavioral tests for depression and anxiety were performed 24 hours after a one-time LPS injection. Biomarkers for pyroptosis-related inflammation cytokines (IL-1β and IL-18) in blood and brains were measured using enzyme-linked immunosorbent assay (ELISA) and immunoblotting, respectively. The changes of primary proteins activation inflammatory pyroptosis (NLRP3: NLR family pyrin domain containing 3, Caspase-1, N-GSDMD: N terminal protein gasdermin D) and synapse proteins (PSD-95 and synpatin-1) in brains were measured using immunoblotting. Intranasal dantrolene nanoparticles robustly inhibited LPS-induced depression and anxiety behavior. Intranasal dantrolene nanoparticles significantly inhibited LPS-induced pathological elevation of IL-1β and IL-18 in the blood and brain and inhibited LPS induced activation of pyroptosis. Intranasal dantrolene nanoparticles significantly ameliorated decrease of PSD-95 and synpatin-1 proteins in brains. Thus, intranasal dantrolene nanoparticles has demonstrated neuroprotection against inflammation mediated depression and anxiety behaviors and should be studied furthermore as a future effective drug treatment of major depression disorder or anxiety psychiatric disorder.
Competing Interest Statement
Drs. Huafeng Wei and Ge Liang are listed as inventors of patent applications entitled Intranasal Administration of Dantrolene for Treatment of Alzheimers Disease in multiple countries by The Trustees of the University of Pennsylvania.
Footnotes
Update on Experimental Grouping and New Data added.
