Protective Role of Lactobacillus rhamnosus Probiotic in Reversing Cocaine-Induced Oxidative Stress, Glial Activation and Locomotion in Mice

Ernest T. Chivero, Susmita Sil, Seema Singh, Annadurai Thangaraj, Lila Gordon, Grace B. Evah-Nzoughe, Natasha Ferguson, Shannon Callen, Shilpa Buch

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Cocaine abuse is known to cause inflammation, oxidative injury and alterations in the gut microbiota. Although emerging studies have demonstrated the role of gut microbiota in modulating neurological complications and behavior, the mechanism(s) underlying these processes remain unclear. In the present study, we investigated the protective effect of Lactobacillus rhamnosus probiotic on cocaine-induced oxidative stress, glial activation, and locomotion in mice. In this study, groups of male C56BL6 mice were administered gut-resident commensal bacteria L. rhamnosus probiotic (oral gavage) concurrently with cocaine (20 mg/kg, i.p.) or saline for 28 days and assessed for oxidative stress and cellular activation in both the gut and brain as well as alterations in locomotion behavior. Cocaine-induced gut dysregulation was associated with increased formation of 4-hydroxynonenal (4-HNE) adducts, increased expression of pERK-1/2, pNF-kB-p65 and antioxidant mediators (SOD1, GPx1). In cocaine administered mice, there was increased activation of both microglia and astrocytes in the striatum and cortex of the brain as shown by enhanced expression of CD11b and GFAP, respectively. Cocaine administration also resulted in increased locomotor activity in the open field test in these mice. Administration of L. rhamnosus attenuated cocaine-induced gut oxidative stress and inflammation as well as glial activation and locomotion. These results suggest the potential of microbial-based interventions to attenuate cocaine-mediated behavioral responses and neuroinflammation, in addition to systemic inflammation and oxidative damage. Graphical Abstract: [Figure not available: see fulltext.].

Original languageEnglish (US)
JournalJournal of Neuroimmune Pharmacology
DOIs
StateAccepted/In press - 2021

Keywords

  • Cocaine
  • Gut-brain axis
  • Lactobacillus rhamnosus
  • Probiotic
  • Reactive oxygen species

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Immunology and Allergy
  • Immunology
  • Pharmacology

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