Microbial glutamate metabolism predicts intravenous cocaine self-administration in diversity outbred mice

Tran, Thi Dong Binh; Nguyen, Hoan; Sodergren, Erica; Addiction, Center For Systems Neurogenetics Of; Dickson, Price E.; Wright, Susan N.; Philip, Vivek; Weinstock, George M.; Chesler, Elissa J.; Zhou, Yanjiao; Bubier, Jason A

doi:10.1016/j.neuropharm.2022.109409

Cited by 10 publications

(6 citation statements)

References 74 publications

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“…Glutamate is also the substrate for GABA production and GABA producing strains such as Lactococcus lactis have been shown to modulate behavior 39 . The finding that glutamate metabolism is altered in response to cocaine in responsive strains supports the glutamate hypothesis of substance use disorder, 40–42 and was supported by our recent findings in the Diversity Outbred Mice 43 extending that process into the gut. These observations provide some mechanistic insight into the gut‐brain axis and SUD.…”

Section: Discussionsupporting

confidence: 71%

The microbial community dynamics of cocaine sensitization in two behaviorally divergent strains of collaborative cross mice

Tran,

Monroy Hernandez,

Nguyen

et al. 2023

Genes Brain and Behavior

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The gut-brain axis is increasingly recognized as an important pathway involved in cocaine use disorder. Microbial products of the murine gut have been shown to affect striatal gene expression, and depletion of the microbiome by antibiotic treatment alters cocaine-induced behavioral sensitization in C57BL/6J male mice. Some reports suggest that cocaine-induced behavioral sensitization is correlated with drug selfadministration behavior in mice. Here, we profile the composition of the naïve micro-

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Section: Discussionsupporting

confidence: 71%

The microbial community dynamics of cocaine sensitization in two behaviorally divergent strains of collaborative cross mice

Tran,

Monroy Hernandez,

Nguyen

et al. 2023

Genes Brain and Behavior

Self Cite

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show abstract

“…Glutamate is also the substrate for GABA production and GABA producing strains such as Lactococcus lactis have been shown to modulate behavior [39]. The finding that glutamate metabolism is altered in response to cocaine in responsive strains supports the glutamate hypothesis of substance use disorder [40-42], and was supported by our recent findings in the Diversity Outbred Mice [43] extending that process into the gut. These observations provide some mechanistic insight into the gut-brain axis and SUD.…”

Section: Discussionmentioning

confidence: 70%

The microbial community dynamics of cocaine sensitization in two behaviorally divergent strains of collaborative cross mice

Tran

Hernandez

Nguyen

et al. 2022

Preprint

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The gut microbiome-brain axis is increasingly recognized as an important pathway in regulation of cocaine addiction. Microbial products produced in the murine gut have been shown to affect striatal gene expression, and depletion of the microbiome by antibiotic treatment alters cocaine-induced behavioral sensitization in C57BL/6J male mice. Cocaine-induced behavioral sensitization is correlated with drug self-administration behavior, therefore, is a predictor of addiction vulnerability. Here we profile the composition of the naïve microbiome and its response to cocaine sensitization in two Collaborative Cross (CC) strains. These strains display extremely divergent behavioral responses to cocaine sensitization. A high-responding strain, CC004/TauUncJ (CC04), has a gut microbiome that contains a greater amount ofLactobacillusthan the cocaine-nonresponsive strain CC041/TauUncJ (CC41). The gut microbiome of CC41 is characterized by an abundance ofEisenbergella, RobinsonellaandRuminococcus. In response to cocaine, CC04 has an increasedBarnsiellapopulation, while the gut microbiome of CC41 displays no significant changes. PICRUSt functional analysis of the functional potential of the gut microbiome in CC04 shows a significant number of Gut-Brain Modules altered after exposure to cocaine, specifically those encoding for tryptophan synthesis, glutamine metabolism, and menaquinone synthesis (vitamin K2). Depletion of the microbiome by antibiotic treatment revealed a sex-specific altered cocaine-sensitization response to antibiotics in female mice from CC04 that was not observed in male CC04 or either sex of CC41. Together these data suggest a complex relationship between host genetics, microbiome composition and cocaine sensitization behavior.FUNDINGU01DA043809 to JAB, GMW P50DA039841 to EJC

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“…Expanding these observations in multiple inbred mouse strains is cumbersome, but the question still remains. In that direction, DO mice have been used to study the influence of genetic factors on disease susceptibility [ 35 ], physiology [ 36 , 37 ], autoimmunity [ 38 ], metabolism [ 39 , 40 ], vaccine response [ 41 , 42 ], behavior [ 43 , 44 ], and toxicity studies [ 45 , 46 ]. Thus, we sought to use DO mice due to their broad genetic diversity, which covers 90% of the available variation in the Mus musculus species [ 47 ] that are maintained as an outbred population [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

Mt10 Vaccine Protects Diversity Outbred Mice from CVB3 Infection by Producing Virus-Specific Neutralizing Antibodies and Diverse Antibody Isotypes

Rasquinha,

Mone,

Sur

et al. 2024

Vaccines

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Group B coxsackieviruses (CVBs) cause a wide range of diseases in humans, but no vaccines are currently available to prevent these infections. Previously, we had demonstrated that a live attenuated CVB3 vaccine virus, Mutant 10 (Mt10), offers protection against multiple CVB serotypes as evaluated in various inbred mouse strains; however, the applicability of these findings to the outbred human population remains uncertain. To address this issue, we used Diversity Outbred (DO) mice, whose genome is derived from eight inbred mouse strains that may capture the level of genetic diversity of the outbred human population. To determine the efficacy of the Mt10 vaccine, we established the CVB3 infection model in the DO mice. We noted that CVB3 infection resulted mainly in pancreatitis, although viral RNA was detected in both the pancreas and heart. Histologically, the pancreatic lesions comprised of necrosis, post-necrotic atrophy, and lymphocyte infiltration. In evaluating the efficacy of the Mt10 vaccine, both male and female DO mice were completely protected in challenge studies with CVB3, and viral RNA was not detected in the heart or pancreas. Likewise, vaccine recipients of both sexes showed significant levels of virus-neutralizing antibodies. Furthermore, by using the CVB3 viral protein 1, virus-reactive antibodies were found to be diverse in the order of IgG2c, followed by IgG2a, IgG2b/IgG3, and IgG1. Together, the data suggest that the Mt10 vaccine virus can offer protection against CVB infections that may have translational significance.

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Microbial glutamate metabolism predicts intravenous cocaine self-administration in diversity outbred mice

Cited by 10 publications

References 74 publications

The microbial community dynamics of cocaine sensitization in two behaviorally divergent strains of collaborative cross mice

The microbial community dynamics of cocaine sensitization in two behaviorally divergent strains of collaborative cross mice

The microbial community dynamics of cocaine sensitization in two behaviorally divergent strains of collaborative cross mice

Mt10 Vaccine Protects Diversity Outbred Mice from CVB3 Infection by Producing Virus-Specific Neutralizing Antibodies and Diverse Antibody Isotypes

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