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Targeting the brain 5-HT7 receptor to prevent hypomyelination in a rodent model of perinatal white matter injuries.
Bokobza, Cindy; Jacquens, Alice; Guenoun, David; Bianco, Blandine; Galland, Anne; Pispisa, Maxime; Cruz, Alexandra; Zinni, Manuela; Faivre, Valérie; Roumier, Anne; Lebon, Sophie; Vitalis, Tania; Csaba, Zsolt; Le Charpentier, Tifenn; Schwendimann, Leslie; Young-Ten, Pierrette; Degos, Vincent; Monteiro, Patricia; Dournaud, Pascal; Gressens, Pierre; Van Steenwinckel, Juliette.
Afiliación
  • Bokobza C; Université Paris Cité, Inserm, NeuroDiderot, 75019, Paris, France. cindy.bokobza@inserm.fr.
  • Jacquens A; Université Paris Cité, Inserm, NeuroDiderot, 75019, Paris, France.
  • Guenoun D; Department of Anesthesia and Critical Care, APHP-Sorbonne University, Hôpital La Pitié- Salpêtrière, Paris, France.
  • Bianco B; Université Paris Cité, Inserm, NeuroDiderot, 75019, Paris, France.
  • Galland A; Department of Pharmacy, APHP, Hôpital Robert Debré, Université de Paris, Paris, France.
  • Pispisa M; Université Paris Cité, Inserm, NeuroDiderot, 75019, Paris, France.
  • Cruz A; Université Paris Cité, Inserm, NeuroDiderot, 75019, Paris, France.
  • Zinni M; Université Paris Cité, Inserm, NeuroDiderot, 75019, Paris, France.
  • Faivre V; Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.
  • Roumier A; Université Paris Cité, Inserm, NeuroDiderot, 75019, Paris, France.
  • Lebon S; Université Paris Cité, Inserm, NeuroDiderot, 75019, Paris, France.
  • Vitalis T; Sorbonne Université, Inserm, UMR-S 1270, Paris, France.
  • Csaba Z; Université Paris Cité, Inserm, NeuroDiderot, 75019, Paris, France.
  • Le Charpentier T; Université Paris Cité, Inserm, NeuroDiderot, 75019, Paris, France.
  • Schwendimann L; Université Paris Cité, Inserm, NeuroDiderot, 75019, Paris, France.
  • Young-Ten P; Université Paris Cité, Inserm, NeuroDiderot, 75019, Paris, France.
  • Degos V; Université Paris Cité, Inserm, NeuroDiderot, 75019, Paris, France.
  • Monteiro P; Université Paris Cité, Inserm, NeuroDiderot, 75019, Paris, France.
  • Dournaud P; Department of Anesthesia and Critical Care, APHP-Sorbonne University, Hôpital La Pitié- Salpêtrière, Paris, France.
  • Gressens P; Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.
  • Van Steenwinckel J; Université Paris Cité, Inserm, NeuroDiderot, 75019, Paris, France.
J Neural Transm (Vienna) ; 130(3): 281-297, 2023 03.
Article en En | MEDLINE | ID: mdl-36335540
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-1ß 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-1ß-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-1ß, 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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Lesiones Encefálicas / Nacimiento Prematuro / Sustancia Blanca Límite: Animals / Child / Female / Humans / Newborn / Pregnancy Idioma: En Revista: J Neural Transm (Vienna) Año: 2023 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Austria
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Lesiones Encefálicas / Nacimiento Prematuro / Sustancia Blanca Límite: Animals / Child / Female / Humans / Newborn / Pregnancy Idioma: En Revista: J Neural Transm (Vienna) Año: 2023 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Austria