Dual Role of the P2X7 Receptor in Dendritic Outgrowth during Physiological and Pathological Brain Development.
ATP
P2X7
Sholl analysis
behavior
dendrites
schizophrenia
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
ISSN: 1529-2401
Titre abrégé: J Neurosci
Pays: United States
ID NLM: 8102140
Informations de publication
Date de publication:
15 02 2023
15 02 2023
Historique:
received:
22
04
2022
revised:
11
11
2022
accepted:
15
11
2022
pubmed:
3
2
2023
medline:
22
2
2023
entrez:
2
2
2023
Statut:
ppublish
Résumé
At high levels, extracellular ATP operates as a "danger" molecule under pathologic conditions through purinergic receptors, including the ionotropic P2X7 receptor (P2X7R). Its endogenous activation is associated with neurodevelopmental disorders; however, its function during early embryonic stages remains largely unclear. Our objective was to determine the role of P2X7R in the regulation of neuronal outgrowth. For this purpose, we performed Sholl analysis of dendritic branches on primary hippocampal neurons and in acute hippocampal slices from WT mice and mice with genetic deficiency or pharmacological blockade of P2X7R. Because abnormal dendritic branching is a hallmark of certain neurodevelopmental disorders, such as schizophrenia, a model of maternal immune activation (MIA)-induced schizophrenia, was used for further morphologic investigations. Subsequently, we studied MIA-induced behavioral deficits in young adult mice females and males. Genetic deficiency or pharmacological blockade of P2X7R led to branching deficits under physiological conditions. Moreover, pathologic activation of the receptor led to deficits in dendritic outgrowth on primary neurons from WT mice but not those from P2X7R KO mice exposed to MIA. Likewise, only MIA-exposed WT mice displayed schizophrenia-like behavioral and cognitive deficits. Therefore, we conclude that P2X7R has different roles in the development of hippocampal dendritic arborization under physiological and pathologic conditions.
Identifiants
pubmed: 36732073
pii: JNEUROSCI.0805-22.2022
doi: 10.1523/JNEUROSCI.0805-22.2022
pmc: PMC9962779
doi:
Substances chimiques
Adenosine Triphosphate
8L70Q75FXE
Receptors, Purinergic P2X7
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1125-1142Informations de copyright
Copyright © 2023 Mut-Arbona et al.
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