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PreprintCited by 2Tryptophan and brain disordersNeuroinflammation and Neurodegeneration MechanismsTreatment of Major Depression

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

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Wei, Huafeng, Liu, Jia, Lu, Yan, Bhuiyan, Piplu, Gruttner, Jacob, Louis, Lauren St., Yi, Yutong, Liang, Ge·2025·Translational Psychiatry
DOI 10.21203/rs.3.rs-6254774/v1PMC PMC12923542

Preprint — published as 10.1038/s41398-026-03816-x · Paper page

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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 an 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 the blood and brain 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 have demonstrated neuroprotection against inflammation-mediated depression and anxiety behaviors and should be studied further as a future effective drug treatment of major depression disorder or anxiety psychiatric disorder.

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Metadata

Authors
Wei, H., Liu, J., Lu, Y., Bhuiyan, P., Gruttner, J., Louis, L. S., Yi, Y., & Liang, G.
Affiliations
  • University of Pennsylvania (US)
  • Affiliated Hospital of Qingdao University (CN)
  • Tongji University (CN)
Corresponding author
Wei, Huafeng
ORCID
Venue
Translational Psychiatry
Publisher
Springer Science and Business Media LLC
Published
2025-04-03
Volume
16
Issue
1
ISSN
2158-3188 (ISSN-L)
DOI
10.21203/rs.3.rs-6254774/v1
PMC
PMC12923542
OpenAlex
W7127307642
Cited by
2
References
1
Citations by year
2025: 2
FWCI
0.00
Type
journal article
Language
en
Open access
Licence
Locations
  • Translational Psychiatry (publishedVersion, cc-by)
  • Research Square (acceptedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed Central (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • University of Pennsylvania
  • Rowan University
  • National Institute on Aging (R01AG061447)
Topics
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
Keywords
intranasal drug delivery, lipopolysaccharide, neuroinflammation, depression, anxiety, pyroptosis, NLRP3 inflammasome, IL-1β, IL-18, PSD-95, synaptic loss, neuroprotection, major depressive disorder, anxiety disorders

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