Targeting the brain 5-HT7 receptor to prevent hypomyelination in a rodent model of perinatal white matter injuries - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Journal of Neural Transmission Année : 2022

Targeting the brain 5-HT7 receptor to prevent hypomyelination in a rodent model of perinatal white matter injuries

Alexandra Cruz
  • Fonction : Auteur
Vincent Degos
  • Fonction : Auteur
Patricia Monteiro
  • Fonction : Auteur

Résumé

Abstract Approximately 15 million babies are born prematurely every year and many will face lifetime motor and/or cognitive deficits. Children born prematurely are at higher risk of developing perinatal brain lesions, especially white matter injuries (WMI). Evidence in humans and rodents demonstrates that systemic inflammation-induced neuroinflammation, including microglial and astrocyte reactivity, is the prominent processes of WMI associated with preterm birth. Thus, a new challenge in the field of perinatal brain injuries is to develop new neuroprotective strategies to target neuroinflammation to prevent WMI. Serotonin (5-HT) and its receptors play an important role in inflammation, and emerging evidence indicates that 5-HT may regulate brain inflammation by the modulation of microglial reactivity and astrocyte functions. The present study is based on a mouse model of WMI induced by intraperitoneal (i.p.) injections of IL-1β during the first 5 days of life. In this model, certain key lesions of preterm brain injuries can be summarized by (i) systemic inflammation, (ii) pro-inflammatory microglial and astrocyte activation, and (iii) inhibition of oligodendrocyte maturation, leading to hypomyelination. We demonstrate that Htr7 mRNA (coding for the HTR7/5-HT7 receptor) is significantly overexpressed in the anterior cortex of IL-1β-exposed animals, suggesting it as a potential therapeutic target. LP-211 is a specific high-affinity HTR7 agonist that crosses the blood–brain barrier (BBB). When co-injected with IL-1β, LP-211 treatment prevented glial reactivity, the down-regulation of myelin-associated proteins, and the apparition of anxiety-like phenotypes. Thus, HTR7 may represent an innovative therapeutic target to protect the developing brain from preterm brain injuries.
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Dates et versions

hal-03970983 , version 1 (03-02-2023)

Identifiants

Citer

Cindy Bokobza, Alice Jacquens, David Guenoun, Blandine Bianco, Anne Galland, et al.. Targeting the brain 5-HT7 receptor to prevent hypomyelination in a rodent model of perinatal white matter injuries. Journal of Neural Transmission, 2022, ⟨10.1007/s00702-022-02556-8⟩. ⟨hal-03970983⟩
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