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bioRxiv · 10.1101/2024.09.06.611461

Intranasal dantrolene nanoparticles inhibit lipopolysaccharide-induced depression and anxiety behavior in mice

Liu, J.·Lu, Y.·Bhuiyan, P.·Gruttner, J.·Louis, L. S.·Yi, Y.·Liang, G.·Wei, H.
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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-1{beta} 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-1{beta} 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.

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Liu, J., Lu, Y., Bhuiyan, P., Gruttner, J., Louis, L. S., Yi, Y., Liang, G., Wei, H.. 2024-09-11. Intranasal dantrolene nanoparticles inhibit lipopolysaccharide-induced depression and anxiety behavior in mice. https://doi.org/10.1101/2024.09.06.611461

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