Chivero Ernest T, Sil Susmita, Singh Seema, Thangaraj Annadurai, Gordon Lila, Evah-Nzoughe Grace B, Ferguson Natasha, Callen Shannon, Buch Shilpa
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
J Neuroimmune Pharmacol. 2022 Jun;17(1-2):62-75. doi: 10.1007/s11481-021-10020-9. Epub 2021 Oct 9.
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.
已知可卡因滥用会导致炎症、氧化损伤以及肠道微生物群的改变。尽管新兴研究已经证明了肠道微生物群在调节神经并发症和行为方面的作用，但这些过程背后的机制仍不清楚。在本研究中，我们调查了鼠李糖乳杆菌益生菌对可卡因诱导的小鼠氧化应激、神经胶质细胞活化和运动的保护作用。在本研究中，将雄性C56BL6小鼠分组，同时给予肠道共生菌鼠李糖乳杆菌益生菌（口服灌胃）和可卡因（20mg/kg，腹腔注射）或生理盐水，持续28天，并评估肠道和大脑中的氧化应激、细胞活化以及运动行为的改变。可卡因诱导的肠道失调与4-羟基壬烯醛（4-HNE）加合物形成增加、pERK-1/2、pNF-κB-p65和抗氧化介质（SOD1、GPx1）表达增加有关。在给予可卡因的小鼠中，大脑纹状体和皮质中的小胶质细胞和星形胶质细胞均被激活，分别表现为CD11b和GFAP表达增强。给予可卡因还导致这些小鼠在旷场试验中的运动活动增加。给予鼠李糖乳杆菌可减轻可卡因诱导的肠道氧化应激和炎症以及神经胶质细胞活化和运动。这些结果表明，基于微生物的干预措施除了可以减轻全身炎症和氧化损伤外，还具有减轻可卡因介导的行为反应和神经炎症的潜力。
