title: Lipopolysaccharide-Induced Behavioral Alterations Are Alleviated by Sodium Phenylbutyrate via Attenuation of Oxidative Stress and Neuroinflammatory Cascade.
abstract: 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.
authors.affiliation: Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education & Research (NIPER), Guwahati, Assam, 781032, India.
authors.forename: Ashok
authors.initials: A
authors.lastname: Jangra
authors.affiliation: Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education & Research (NIPER), Guwahati, Assam, 781032, India.
authors.forename: Chandra Shaker
authors.initials: CS
authors.lastname: Sriram
authors.affiliation: Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education & Research (NIPER), Guwahati, Assam, 781032, India. dr.lahkarniper@gmail.com.|Department of Pharmacology, Gauhati Medical College, Guwahati, Assam, 781032, India. dr.lahkarniper@gmail.com.
authors.forename: Mangala
authors.initials: M
authors.lastname: Lahkar
mesh_terms: D000818:Animals; D001007:Anxiety / Q000188:drug therapy; D001526:Behavioral Symptoms / Q000139:chemically induced / Q000188:drug therapy*; D003863:Depression / Q000188:drug therapy; D004660:Encephalitis / Q000188:drug therapy* / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects*; D010654:Phenylbutyrates / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; C000717248:Hspa5 protein, mouse; D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; D010654:Phenylbutyrates; C075773:4-phenylbutyric acid
keywords: anxiety; depression; hippocampus; lipopolysaccharide; neuroinflammation; oxidative stress