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

Autor: Bokobza C; Université Paris Cité, Inserm, NeuroDiderot, 75019, Paris, France. cindy.bokobza@inserm.fr., Jacquens A; Université Paris Cité, Inserm, NeuroDiderot, 75019, Paris, France.; Department of Anesthesia and Critical Care, APHP-Sorbonne University, Hôpital La Pitié- Salpêtrière, Paris, France., Guenoun D; Université Paris Cité, Inserm, NeuroDiderot, 75019, Paris, France.; Department of Pharmacy, APHP, Hôpital Robert Debré, Université de Paris, Paris, France., Bianco B; Université Paris Cité, Inserm, NeuroDiderot, 75019, Paris, France., Galland A; Université Paris Cité, Inserm, NeuroDiderot, 75019, Paris, France., Pispisa M; Université Paris Cité, Inserm, NeuroDiderot, 75019, Paris, France., Cruz A; Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal., Zinni M; Université Paris Cité, Inserm, NeuroDiderot, 75019, Paris, France., Faivre V; Université Paris Cité, Inserm, NeuroDiderot, 75019, Paris, France., Roumier A; Sorbonne Université, Inserm, UMR-S 1270, Paris, France., Lebon S; Université Paris Cité, Inserm, NeuroDiderot, 75019, Paris, France., Vitalis T; Université Paris Cité, Inserm, NeuroDiderot, 75019, 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; Department of Anesthesia and Critical Care, APHP-Sorbonne University, Hôpital La Pitié- Salpêtrière, Paris, France., Monteiro P; Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal., Dournaud P; Université Paris Cité, Inserm, NeuroDiderot, 75019, Paris, France., Gressens P; Université Paris Cité, Inserm, NeuroDiderot, 75019, Paris, France., Van Steenwinckel J; Université Paris Cité, Inserm, NeuroDiderot, 75019, Paris, France. juliette.van-steenwinckel@inserm.fr.
Jazyk: angličtina
Zdroj: Journal of neural transmission (Vienna, Austria : 1996) [J Neural Transm (Vienna)] 2023 Mar; Vol. 130 (3), pp. 281-297. Date of Electronic Publication: 2022 Nov 06.
DOI: 10.1007/s00702-022-02556-8
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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