, Volume 39, Issue 4, pp 1441–1452 | Cite as

Lipopolysaccharide-Induced Behavioral Alterations Are Alleviated by Sodium Phenylbutyrate via Attenuation of Oxidative Stress and Neuroinflammatory Cascade

  • Ashok Jangra
  • Chandra Shaker Sriram
  • Mangala Lahkar


Oxido-nitrosative stress, neuroinflammation, and reduced level of neurotrophins are implicated in the pathophysiology of anxiety and depressive illness. A few recent studies have revealed the role of endoplasmic reticulum (ER) stress in the pathophysiology of stress and depression. The aim of the present study is to investigate the neuroprotective potential of sodium phenylbutyrate (SPB), an ER stress inhibitor against lipopolysaccharide (LPS)-induced anxiety and depressive-like behavior in Swiss albino mice. Anxiety and depressive-like behavior was induced by LPS (0.83 mg/kg; i.p.) administration. Various behavioral tests were conducted to evaluate the anxiety and depressive-like behavior in mice. Real-time PCR was employed for the detection and expression of ER stress markers (78-kDa glucose-regulated protein (GRP78) and CCAAT/enhancer binding protein homologous protein (CHOP)). Pretreatment with SPB significantly ameliorated the LPS-induced anxiety and depressive-like behavior as revealed by behavioral paradigm results. LPS-induced oxidative stress was ameliorated by SPB pretreatment in hippocampus (HC) and prefrontal cortex (PFC) region. Neuroinflammation was significantly reduced by SPB pretreatment in LPS-treated mice as evident from reduction in proinflammatory cytokines (IL-1β and TNF-α). Importantly, LPS administration significantly up-regulated the GRP78 mRNA expression level in the HC which suggests the involvement of unfolded protein response (UPR) in LPS-evoked behavioral anomalies. These results highlight the neuroprotective potential of SPB in LPS-induced anxiety and depressive illness model which may be partially due to inhibition of oxidative stress-neuroinflammatory cascade.


anxiety depression hippocampus lipopolysaccharide neuroinflammation oxidative stress 



We would like to thank the Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Government of India, for financial support. The authors are immensely thankful to Institutional Level Biotech hub, NIPER Guwahati and State Biotech Hub, College of Veterinary Sciences, Guwahati, for providing technical support.

Compliance with Ethical Standards

Conflict of Interest



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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Ashok Jangra
    • 1
  • Chandra Shaker Sriram
    • 1
  • Mangala Lahkar
    • 1
    • 2
  1. 1.Department of Pharmacology & ToxicologyNational Institute of Pharmaceutical Education & Research (NIPER)GuwahatiIndia
  2. 2.Department of PharmacologyGauhati Medical CollegeGuwahatiIndia

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