The metabolite p-cresol impairs dendritic development, synaptogenesis, and synapse function in hippocampal neurons: Implications for autism spectrum disorder

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dc.catalogadorjlo
dc.contributor.authorGuzmán Salas, Sheyla
dc.contributor.authorWeber, André
dc.contributor.authorMalci, Ayse
dc.contributor.authorLin, Xiao
dc.contributor.authorHerrera Molina, Rodrigo
dc.contributor.authorCerpa Nebott, Waldo Francisco
dc.contributor.authorDorador, Cristina
dc.contributor.authorSignorelli, Janetti
dc.contributor.authorZamorano, Pedro
dc.date.accessioned2024-01-29T17:48:31Z
dc.date.available2024-01-29T17:48:31Z
dc.date.issued2022
dc.description.abstractAutism spectrum disorder (ASD) is a heterogeneous neurodevelopment disorder resulting from different etiological factors, both genetic and/or environmental. These factors can lead to abnormal neuronal development on dendrite and synaptic function at the central nervous system. Recent studies have shown that a subset of ASD patients display increased circulation levels of the tyrosine metabolite, p-cresol, related to chronic intestinal disorders because of dysbiosis of the intestinal microbiota. In particular, abnormal presence of intestinal Clostridium sp. has been linked to high levels of p-cresol in ASD children younger than 8 years. However, the role of p-cresol during development of the central nervous system is unknown. Here, we evaluated in vitro the effect of p-cresol on neurite outgrowth in N2a and PC12 cell lines and dendritic morphology, synaptic density, neuronal activity, and calcium responses in primary rat hippocampal neurons. p-cresol inhibits neural differentiation and neurites outgrowth in N2a and PC12 neuronal cell lines. In hippocampal neuronal cultures, Sholl's analysis shows a decrease in the dendritic arborization of neurons treated with p-cresol. Synaptic density analyzed with the synaptic markers Piccolo and Shank2 is diminished in hippocampal neurons treated with p-cresol. Electrically evoked intracellular calcium rise was drastically, but reversely, blocked by p-cresol, whereas that spontaneous neuronal activity was severely affected by early addition of the metabolite. These findings show that p-cresol alters dendrite development, synaptogenesis, and synapse function of neurons in culture, therefore, neuronal alterations occurring in ASD children may be related to this metabolite and dysbiosis of the intestinal microbiota.
dc.fuente.origenORCID-ene24
dc.identifier.doi10.1111/jnc.15604
dc.identifier.issn0022-3042
dc.identifier.urihttps://doi.org/10.1111/jnc.15604
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/81031
dc.information.autorucFacultad de Ciencias Biológicas; Cerpa Nebott, Waldo Francisco; 0000-0001-7344-0144; 16584
dc.issue.numero4
dc.language.isoen
dc.nota.accesoContenido parcial
dc.pagina.final349
dc.pagina.inicio335
dc.revistaJournal of Neurochemistry
dc.rightsacceso restringido
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.titleThe metabolite p-cresol impairs dendritic development, synaptogenesis, and synapse function in hippocampal neurons: Implications for autism spectrum disorder
dc.typeartículo
dc.volumen161
sipa.codpersvinculados16584
sipa.trazabilidadORCID;2024-01-15
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