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2301 Avenue d’Estimauville Québec (Québec) G1E 0N5 Canada
Professeur adjoint, Département de psychiatrie et de neurosciences, Faculté de médecine
Université Laval
Axe de recherche:
Neurosciences intégratives et thérapies expérimentales
Notre laboratoire utilise le poisson-zèbre pour étudier les mécanismes biologiques contrôlant le comportement avec un emphase sur la dépendance aux opioïdes.
À l’aide de plateforme basée sur le comportement, nous étudions le rôle des neurostéroïdes dans la consommation d’opioïdes et nous utilisons des outils génétiques et pharmacologiques pour identifier de nouvelles voies moléculaires impliquées dans la dépendance aux drogues.
Nous sommes également intéressés à développer un modèle d’exposition prénatale aux opioïdes afin de mesurer les conséquences comportementales et biologiques causées par cette exposition.
Notre plateforme de comportement et de dépendance aux opioïdes est également utilisée afin de réaliser des criblages de petites molécules afin d’identifier de nouvelles molécules neuroactives. Ces molécules et leurs cibles moléculaires ont le potentiel d’identifier de nouveaux sentiers biologiques et de nouvelles approches thérapeutiques pour différentes conditions.
Our group is using zebrafish to study the biological mechanisms involved in controlling behaviour, focusing on opioid addiction.
Using a novel self-administration assay, we are studying the role of neurosteroids in opioid intake and using a combination of pharmacology, genetics, and imaging methods to identify novel biological pathways involves in drug addiction.
We are also developing a new model to study the biological and behavioural consequences of neonatal opioid exposure in zebrafish.
Our behaviour-based platform is also used to perform small molecule screening to identify novel neuroactive molecules. The compounds uncovered and their cellular targets have the potential to uncover novel pathways and therapeutic approaches, as I have already shown with finasteride.
Margaux Caperaa; Mathilde Roland-Caverivière; Chelsea Herdman; Nesrine Imloul; Sandrine Poulin; Mado Lemieux; Paul De Koninck; Gabriel D Bossé
Development of sensorimotor responses in larval zebrafish: A comparison between wild-type and GCaMP6s transgenic line Article de journal
Dans: Behav Brain Res, vol. 481, p. 115412, 2025, ISSN: 1872-7549.
@article{pmid39746401,
title = {Development of sensorimotor responses in larval zebrafish: A comparison between wild-type and GCaMP6s transgenic line},
author = {Margaux Caperaa and Mathilde Roland-Caverivière and Chelsea Herdman and Nesrine Imloul and Sandrine Poulin and Mado Lemieux and Paul De Koninck and Gabriel D Bossé},
doi = {10.1016/j.bbr.2024.115412},
issn = {1872-7549},
year = {2025},
date = {2025-03-01},
journal = {Behav Brain Res},
volume = {481},
pages = {115412},
abstract = {During early development, zebrafish larvae exhibit stereotypical behaviors, which rapidly become more complex. Thus, generating mutant transgenic lines that maintain transparency throughout their larval stage and that can be used to record brain activity has offered strategic opportunities to investigate the underlying neural correlates of behavior establishment. However, few studies have documented the sensorimotor profile of these lines during larval development. Here, we set up a behavioral characterization using diverse stimuli (light and vibration) throughout larval development to compare the responses of a transgenic strain expressing a pan-neuronal calcium indicator (GCaMP6s) with that of a wild-type strain. Interestingly, we report a drastic switch in behavioral responses to light transitions at 11 days post-fertilization (dpf) and to vibration stimuli at 14 dpf in both lines. These data highlight a specific time window representing an increase in behavioral complexity. Meanwhile, we found some differences in the maturation of sensorimotor responses between GCaMP6s and wild-type strains. Although some of these differences are minor, they highlight the need for careful attention when using mutant/transgenic lines for behavioral studies. Overall, our results support using GCaMP6s strain in investigating the neural mechanisms underlying the developmental maturation of sensorimotor responses.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Stephanie A Carmack; Janaina C M Vendruscolo; M Adrienne McGinn; Jorge Miranda-Barrientos; Vez Repunte-Canonigo; Gabriel D Bosse; Daniele Mercatelli; Federico M Giorgi; Yu Fu; Anthony J Hinrich; Francine M Jodelka; Karen Ling; Robert O Messing; Randall T Peterson; Frank Rigo; Scott Edwards; Pietro P Sanna; Marisela Morales; Michelle L Hastings; George F Koob; Leandro F Vendruscolo
Corticosteroid sensitization drives opioid addiction Article de journal
Dans: Mol Psychiatry, vol. 27, no 5, p. 2492–2501, 2022, ISSN: 1476-5578.
@article{pmid35296810,
title = {Corticosteroid sensitization drives opioid addiction},
author = {Stephanie A Carmack and Janaina C M Vendruscolo and M Adrienne McGinn and Jorge Miranda-Barrientos and Vez Repunte-Canonigo and Gabriel D Bosse and Daniele Mercatelli and Federico M Giorgi and Yu Fu and Anthony J Hinrich and Francine M Jodelka and Karen Ling and Robert O Messing and Randall T Peterson and Frank Rigo and Scott Edwards and Pietro P Sanna and Marisela Morales and Michelle L Hastings and George F Koob and Leandro F Vendruscolo},
doi = {10.1038/s41380-022-01501-1},
issn = {1476-5578},
year = {2022},
date = {2022-05-01},
journal = {Mol Psychiatry},
volume = {27},
number = {5},
pages = {2492--2501},
abstract = {The global crisis of opioid overdose fatalities has led to an urgent search to discover the neurobiological mechanisms of opioid use disorder (OUD). A driving force for OUD is the dysphoric and emotionally painful state (hyperkatifeia) that is produced during acute and protracted opioid withdrawal. Here, we explored a mechanistic role for extrahypothalamic stress systems in driving opioid addiction. We found that glucocorticoid receptor (GR) antagonism with mifepristone reduced opioid addiction-like behaviors in rats and zebrafish of both sexes and decreased the firing of corticotropin-releasing factor neurons in the rat amygdala (i.e., a marker of brain stress system activation). In support of the hypothesized role of glucocorticoid transcriptional regulation of extrahypothalamic GRs in addiction-like behavior, an intra-amygdala infusion of an antisense oligonucleotide that blocked GR transcriptional activity reduced addiction-like behaviors. Finally, we identified transcriptional adaptations of GR signaling in the amygdala of humans with OUD. Thus, GRs, their coregulators, and downstream systems may represent viable therapeutic targets to treat the "stress side" of OUD.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Gabriel D Bosse; Roberto Cadeddu; Gabriele Floris; Ryan D Farero; Eva Vigato; Suhjung J Lee; Tejia Zhang; Nilesh W Gaikwad; Kristen A Keefe; Paul Em Phillips; Marco Bortolato; Randall T Peterson
The 5α-reductase inhibitor finasteride reduces opioid self-administration in animal models of opioid use disorder Article de journal
Dans: J Clin Invest, vol. 131, no 10, 2021, ISSN: 1558-8238.
@article{pmid33848264,
title = {The 5α-reductase inhibitor finasteride reduces opioid self-administration in animal models of opioid use disorder},
author = {Gabriel D Bosse and Roberto Cadeddu and Gabriele Floris and Ryan D Farero and Eva Vigato and Suhjung J Lee and Tejia Zhang and Nilesh W Gaikwad and Kristen A Keefe and Paul Em Phillips and Marco Bortolato and Randall T Peterson},
doi = {10.1172/JCI143990},
issn = {1558-8238},
year = {2021},
date = {2021-05-01},
journal = {J Clin Invest},
volume = {131},
number = {10},
abstract = {Opioid use disorder (OUD) has become a leading cause of death in the United States, yet current therapeutic strategies remain highly inadequate. To identify potential treatments for OUD, we screened a targeted selection of over 100 drugs using a recently developed opioid self-administration assay in zebrafish. This paradigm showed that finasteride, a steroidogenesis inhibitor approved for the treatment of benign prostatic hyperplasia and androgenetic alopecia, reduced self-administration of multiple opioids without affecting locomotion or feeding behavior. These findings were confirmed in rats; furthermore, finasteride reduced the physical signs associated with opioid withdrawal. In rat models of neuropathic pain, finasteride did not alter the antinociceptive effect of opioids and reduced withdrawal-induced hyperalgesia. Steroidomic analyses of the brains of fish treated with finasteride revealed a significant increase in dehydroepiandrosterone sulfate (DHEAS). Treatment with precursors of DHEAS reduced opioid self-administration in zebrafish in a fashion akin to the effects of finasteride. These results highlight the importance of steroidogenic pathways as a rich source of therapeutic targets for OUD and point to the potential of finasteride as a new treatment option for this disorder.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Gabriel D Bosse; Cristoval Urcino; Maren Watkins; Paula Flórez Salcedo; Sabrina Kozel; Kevin Chase; April Cabang; Samuel S Espino; Helena Safavi-Hemami; Shrinivasan Raghuraman; Baldomero M Olivera; Randall T Peterson; Joanna Gajewiak
Discovery of a Potent Conorfamide from Using a Novel Zebrafish Larvae Assay Article de journal
Dans: J Nat Prod, vol. 84, no 4, p. 1232–1243, 2021, ISSN: 1520-6025.
@article{pmid33764053,
title = {Discovery of a Potent Conorfamide from Using a Novel Zebrafish Larvae Assay},
author = {Gabriel D Bosse and Cristoval Urcino and Maren Watkins and Paula Flórez Salcedo and Sabrina Kozel and Kevin Chase and April Cabang and Samuel S Espino and Helena Safavi-Hemami and Shrinivasan Raghuraman and Baldomero M Olivera and Randall T Peterson and Joanna Gajewiak},
doi = {10.1021/acs.jnatprod.0c01297},
issn = {1520-6025},
year = {2021},
date = {2021-04-01},
journal = {J Nat Prod},
volume = {84},
number = {4},
pages = {1232--1243},
abstract = {Natural products such as conotoxins have tremendous potential as tools for biomedical research and for the treatment of different human diseases. Conotoxins are peptides present in the venoms of predatory cone snails that have a rich diversity of pharmacological functions. One of the major bottlenecks in natural products research is the rapid identification and evaluation of bioactive molecules. To overcome this limitation, we designed a set of light-induced behavioral assays in zebrafish larvae to screen for bioactive conotoxins. We used this screening approach to test several unique conotoxins derived from different cone snail clades and discovered that a conorfamide from , CNF-Ep1, had the most dramatic alterations in the locomotor behavior of zebrafish larvae. Interestingly, CNF-Ep1 is also bioactive in several mouse assay systems when tested and . Our novel screening platform can thus accelerate the identification of bioactive marine natural products, and the first compound discovered using this assay has intriguing properties that may uncover novel neuronal circuitry.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Olivia Weeks; Gabriel D Bossé; Isaac M Oderberg; Sebastian Akle; Yariv Houvras; Paul J Wrighton; Kyle LaBella; Isabelle Iversen; Sahar Tavakoli; Isaac Adatto; Arkadi Schwartz; Daan Kloosterman; Allison Tsomides; Michael E Charness; Randall T Peterson; Matthew L Steinhauser; Pouneh K Fazeli; Wolfram Goessling
Fetal alcohol spectrum disorder predisposes to metabolic abnormalities in adulthood Article de journal
Dans: J Clin Invest, vol. 130, no 5, p. 2252–2269, 2020, ISSN: 1558-8238.
@article{pmid32202514,
title = {Fetal alcohol spectrum disorder predisposes to metabolic abnormalities in adulthood},
author = {Olivia Weeks and Gabriel D Bossé and Isaac M Oderberg and Sebastian Akle and Yariv Houvras and Paul J Wrighton and Kyle LaBella and Isabelle Iversen and Sahar Tavakoli and Isaac Adatto and Arkadi Schwartz and Daan Kloosterman and Allison Tsomides and Michael E Charness and Randall T Peterson and Matthew L Steinhauser and Pouneh K Fazeli and Wolfram Goessling},
doi = {10.1172/JCI132139},
issn = {1558-8238},
year = {2020},
date = {2020-05-01},
journal = {J Clin Invest},
volume = {130},
number = {5},
pages = {2252--2269},
abstract = {Prenatal alcohol exposure (PAE) affects at least 10% of newborns globally and leads to the development of fetal alcohol spectrum disorders (FASDs). Despite its high incidence, there is no consensus on the implications of PAE on metabolic disease risk in adults. Here, we describe a cohort of adults with FASDs that had an increased incidence of metabolic abnormalities, including type 2 diabetes, low HDL, high triglycerides, and female-specific overweight and obesity. Using a zebrafish model for PAE, we performed population studies to elucidate the metabolic disease seen in the clinical cohort. Embryonic alcohol exposure (EAE) in male zebrafish increased the propensity for diet-induced obesity and fasting hyperglycemia in adulthood. We identified several consequences of EAE that may contribute to these phenotypes, including a reduction in adult locomotor activity, alterations in visceral adipose tissue and hepatic development, and persistent diet-responsive transcriptional changes. Taken together, our findings define metabolic vulnerabilities due to EAE and provide evidence that behavioral changes and primary organ dysfunction contribute to resultant metabolic abnormalities.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Gabriel D Bossé; Randall T Peterson
Development of an opioid self-administration assay to study drug seeking in zebrafish Article de journal
Dans: Behav Brain Res, vol. 335, p. 158–166, 2017, ISSN: 1872-7549.
@article{pmid28811180,
title = {Development of an opioid self-administration assay to study drug seeking in zebrafish},
author = {Gabriel D Bossé and Randall T Peterson},
doi = {10.1016/j.bbr.2017.08.001},
issn = {1872-7549},
year = {2017},
date = {2017-09-01},
journal = {Behav Brain Res},
volume = {335},
pages = {158--166},
abstract = {The zebrafish (Danio rerio) has become an excellent tool to study mental health disorders, due to its physiological and genetic similarity to humans, ease of genetic manipulation, and feasibility of small molecule screening. Zebrafish have been shown to exhibit characteristics of addiction to drugs of abuse in non-contingent assays, including conditioned place preference, but contingent assays have been limited to a single assay for alcohol consumption. Using inexpensive electronic, mechanical, and optical components, we developed an automated opioid self-administration assay for zebrafish, enabling us to measure drug seeking and gain insight into the underlying biological pathways. Zebrafish trained in the assay for five days exhibited robust self-administration, which was dependent on the function of the μ-opioid receptor. In addition, a progressive ratio protocol was used to test conditioned animals for motivation. Furthermore, conditioned fish continued to seek the drug despite an adverse consequence and showed signs of stress and anxiety upon withdrawal of the drug. Finally, we validated our assay by confirming that self-administration in zebrafish is dependent on several of the same molecular pathways as in other animal models. Given the ease and throughput of this assay, it will enable identification of important biological pathways regulating drug seeking and could lead to the development of new therapeutic molecules to treat addiction.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Chris Wang; Pratyush Gupta; Lucile Fressigne; Gabriel D Bossé; Xin Wang; Martin J Simard; Dave Hansen
TEG-1 CD2BP2 controls miRNA levels by regulating miRISC stability in C. elegans and human cells Article de journal
Dans: Nucleic Acids Res, vol. 45, no 3, p. 1488–1500, 2017, ISSN: 1362-4962.
@article{pmid28180320,
title = {TEG-1 CD2BP2 controls miRNA levels by regulating miRISC stability in C. elegans and human cells},
author = {Chris Wang and Pratyush Gupta and Lucile Fressigne and Gabriel D Bossé and Xin Wang and Martin J Simard and Dave Hansen},
doi = {10.1093/nar/gkw836},
issn = {1362-4962},
year = {2017},
date = {2017-02-01},
journal = {Nucleic Acids Res},
volume = {45},
number = {3},
pages = {1488--1500},
abstract = {MiRNAs post-transcriptionally regulate gene expression by recruiting the miRNA-induced silencing complex (miRISC) to target mRNAs. However, the mechanisms by which miRISC components are maintained at appropriate levels for proper function are largely unknown. Here, we demonstrate that Caenorhabditis elegans TEG-1 regulates the stability of two miRISC effectors, VIG-1 and ALG-1, which in turn affects the abundance of miRNAs in various families. We demonstrate that TEG-1 physically interacts with VIG-1, and complexes with mature let-7 miRNA. Also, loss of teg-1 in vivo phenocopies heterochronic defects observed in let-7 mutants, suggesting the association of TEG-1 with miRISC is necessary for let-7 to function properly during development. Loss of TEG-1 function also affects the abundance and function of other microRNAs, suggesting that TEG-1's role is not specific to let-7. We further demonstrate that the human orthologs of TEG-1, VIG-1 and ALG-1 (CD2BP2, SERBP1/PAI-RBP1 and AGO2) are found in a complex in HeLa cells, and knockdown of CD2BP2 results in reduced miRNA levels; therefore, TEG-1's role in affecting miRNA levels and function is likely conserved. Together, these data demonstrate that TEG-1 CD2BP2 stabilizes miRISC and mature miRNAs, maintaining them at levels necessary to properly regulate target gene expression.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Oussama Meziane; Sandra Piquet; Gabriel D Bossé; Dominic Gagné; Eric Paquet; Claude Robert; Michael A Tones; Martin J Simard
The human decapping scavenger enzyme DcpS modulates microRNA turnover Article de journal
Dans: Sci Rep, vol. 5, p. 16688, 2015, ISSN: 2045-2322.
@article{pmid26584588,
title = {The human decapping scavenger enzyme DcpS modulates microRNA turnover},
author = {Oussama Meziane and Sandra Piquet and Gabriel D Bossé and Dominic Gagné and Eric Paquet and Claude Robert and Michael A Tones and Martin J Simard},
doi = {10.1038/srep16688},
issn = {2045-2322},
year = {2015},
date = {2015-11-01},
journal = {Sci Rep},
volume = {5},
pages = {16688},
abstract = {The decapping scavenger enzyme DcpS is known for its role in hydrolyzing the cap structure following mRNA degradation. Recently, we discovered a new function in miRNA degradation activation for the ortholog of DcpS in C. elegans. Here we show that human DcpS conserves its role in miRNA turnover. In human cells, DcpS is a nucleocytoplasmic shuttling protein that activates miRNA degradation independently of its scavenger decapping activity in the cytoplasmic compartment. We also demonstrate that this new function for DcpS requires the contribution of the 5'-3' exonuclease Xrn2. Our findings support a conserved role of DcpS as a modulator of miRNA turnover in animals.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Alejandro Vasquez-Rifo; Gabriel D Bossé; Evelyne L Rondeau; Guillaume Jannot; Alexandra Dallaire; Martin J Simard
A new role for the GARP complex in microRNA-mediated gene regulation Article de journal
Dans: PLoS Genet, vol. 9, no 11, p. e1003961, 2013, ISSN: 1553-7404.
@article{pmid24244204,
title = {A new role for the GARP complex in microRNA-mediated gene regulation},
author = {Alejandro Vasquez-Rifo and Gabriel D Bossé and Evelyne L Rondeau and Guillaume Jannot and Alexandra Dallaire and Martin J Simard},
doi = {10.1371/journal.pgen.1003961},
issn = {1553-7404},
year = {2013},
date = {2013-11-01},
journal = {PLoS Genet},
volume = {9},
number = {11},
pages = {e1003961},
abstract = {Many core components of the microRNA pathway have been elucidated and knowledge of their mechanisms of action actively progresses. In contrast, factors with modulatory roles on the pathway are just starting to become known and understood. Using a genetic screen in Caenorhabditis elegans, we identify a component of the GARP (Golgi Associated Retrograde Protein) complex, vps-52, as a novel genetic interactor of the microRNA pathway. The loss of vps-52 in distinct sensitized genetic backgrounds induces the enhancement of defective microRNA-mediated gene silencing. It synergizes with the core microRNA components, alg-1 Argonaute and ain-1 (GW182), in enhancing seam cell defects and exacerbates the gene silencing defects of the let-7 family and lsy-6 microRNAs in the regulation of seam cell, vulva and ASEL neuron development. Underpinning the observed genetic interactions, we found that VPS-52 impinges on the abundance of the GW182 proteins as well as the levels of microRNAs including the let-7 family. Altogether, we demonstrate that GARP complex fulfills a positive modulatory role on microRNA function and postulate that acting through GARP, vps-52 participates in a membrane-related process of the microRNA pathway.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Gabriel D Bossé; Stefan Rüegger; Maria C Ow; Alejandro Vasquez-Rifo; Evelyne L Rondeau; Victor R Ambros; Helge Grosshans; Martin J Simard
The decapping scavenger enzyme DCS-1 controls microRNA levels in Caenorhabditis elegans Article de journal
Dans: Mol Cell, vol. 50, no 2, p. 281–287, 2013, ISSN: 1097-4164.
@article{pmid23541767,
title = {The decapping scavenger enzyme DCS-1 controls microRNA levels in Caenorhabditis elegans},
author = {Gabriel D Bossé and Stefan Rüegger and Maria C Ow and Alejandro Vasquez-Rifo and Evelyne L Rondeau and Victor R Ambros and Helge Grosshans and Martin J Simard},
doi = {10.1016/j.molcel.2013.02.023},
issn = {1097-4164},
year = {2013},
date = {2013-04-01},
journal = {Mol Cell},
volume = {50},
number = {2},
pages = {281--287},
abstract = {In metazoans, microRNAs play a critical role in the posttranscriptional regulation of genes required for cell proliferation and differentiation. MicroRNAs themselves are regulated by a multitude of mechanisms influencing their transcription and posttranscriptional maturation. However, there is only sparse knowledge on pathways regulating the mature, functional form of microRNA. Here, we uncover the implication of the decapping scavenger protein DCS-1 in the control of microRNA turnover. In Caenorhabditis elegans, mutations in dcs-1 increase the levels of functional microRNAs. We demonstrate that DCS-1 interacts with the exonuclease XRN-1 to promote microRNA degradation in an independent manner from its known decapping scavenger activity, establishing two molecular functions for DCS-1. Our findings thus indicate that DCS-1 is part of a degradation complex that performs microRNA turnover in animals.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
