Neuroglycobiologie du stress périnatal : contribution de l'axe stress RE (réticulum endoplasmiq[...]

Overview (French)

Le stress périnatal (PRS) est un facteur majeur de vulnérabilité aux troubles addictifs et aux altérations du sommeil. Dans notre modèle de rat PRS, nous avons mis en évidence une sensibilité accrue aux faibles concentrations d'éthanol, des profils de consommation et de rechute spécifiques du sexe et de l'âge, ainsi qu'un couplage étroit entre sommeil paradoxal (REM), corticosterone et alcool, accompagné d'une altération de la plasticité dendritique hippocampique, particulièrement marquée chez les femelles. En parallèle, des données préliminaires suggèrent qu'un mécanisme de neuroglycosylation pourrait contribuer à cette vulnérabilité : le PRS dérégulerait l'axe stress du réticulum endoplasmique (RE)–réponse UPR (notamment la voie PERK–eIF2α) et modifierait l'expression de plusieurs enzymes de sialylation (ST3GAL1, ST3GAL4, ST6GAL1) dans l'hippocampe ventral de rats exposés à l'alcool. Ce profil indiquerait une maturation anormale des N-glycanes et des récepteurs synaptiques, susceptible d'altérer des systèmes neurochimiques clés impliqués dans la récompense, le stress et la régulation du sommeil.

Overview (English)

Perinatal stress (PRS) is a major risk factor for vulnerability to addictive disorders and sleep alterations. In our PRS rat model, we have shown increased sensitivity to low ethanol concentrations, sex- and age-dependent drinking and relapse profiles, and a tight coupling between rapid eye movement (REM) sleep, corticosterone levels and alcohol intake, together with altered hippocampal dendritic spine plasticity, particularly marked in females. In parallel, preliminary data suggest that a neuroglycosylation mechanism may contribute to this vulnerability: PRS appears to dysregulate the endoplasmic reticulum (ER) stress–unfolded protein response (UPR) axis (notably the PERK–eIF2α pathway) and modify the expression of several sialyltransferases (ST3GAL1, ST3GAL4, ST6GAL1) in the ventral hippocampus of alcohol-exposed rats. This profile indicates abnormal maturation of N-glycans and synaptic receptors, potentially impairing key neurochemical systems involved in reward, stress and sleep regulation.

PhD Objectives

From an integrative neuroglycobiology perspective, the objectives of this PhD project are:

1. to characterize how the ER stress–UPR/N-glycosylation axis durably reprograms brain circuits (hippocampus, striatum, prefrontal cortex and other relevant structures) after PRS;
2. to understand how these alterations sustain sex- and age-dependent alcohol-related phenotypes.

Leveraging an already phenotyped cohort (alcohol intake, relapse, sleep architecture) and preserved brain structures, the PhD student will perform targeted analyses of UPR signaling, glycogenes and N/O-glycan profiles, as well as glycosylation of dopaminergic, glutamatergic and GABAergic receptors. Multivariate integration of molecular, behavioral and physiological datasets will enable the identification of glyco-UPR signatures associated with resilience or vulnerability to alcohol, thereby opening new therapeutic perspectives targeting neuroglycobiological pathways in alcohol-related disorders.

Responsibilities and Scope

• Conduct targeted analyses of UPR signaling, glycogenes and N/O-glycan profiles in rat brain tissues.
• Perform glycosylation studies of dopaminergic, glutamatergic, and GABAergic receptors.
• Integrate molecular, behavioral, and physiological datasets using multivariate methods.
• Identify glyco-UPR signatures linked to resilience or vulnerability to alcohol.
• Collaborate within an inter-disciplinary research environment.

Requirements and Qualifications

• Master 2 (M2) in Neuroscience, Biology-Health, Cellular and Molecular Biology, or an equivalent discipline.
• Strong motivation and scientific curiosity with critical thinking and independent work capability.
• Prior experience in molecular and cellular biology techniques (qPCR, Western blot, immunodetection) or protein biochemistry.
• Knowledge in integrative neuroscience, synaptic plasticity, reward circuits, stress physiology, or glycobiology is a plus.
• Competency or willingness to learn statistical and data analysis tools (GraphPad Prism, Python, MetaboAnalyst, or equivalents).
• Good written and oral communication skills in English.
• Capacity for long-term experimental and analytical work with perseverance, adaptability, and integrity.

Contract Details

Début de la thèse : 01/10/2026Funding category: Contrat doctoralConcours pour un contrat doctoral

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