Glyphosate impairs both structure and function of GABAergic synapses in hippocampal neurons

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dc.authoridGiustetto, Maurizio/0000-0003-1323-4060
dc.authoridChiantia, Giuseppe/0000-0001-7971-4994
dc.authoridMARCANTONI, Andrea/0000-0001-5825-7827
dc.authoridHidisoglu, Enis/0000-0002-1729-1209
dc.contributor.authorChiantia, Giuseppe
dc.contributor.authorComai, Debora
dc.contributor.authorHidisoglu, Enis
dc.contributor.authorGurgone, Antonia
dc.contributor.authorFranchino, Claudio
dc.contributor.authorCarabelli, Valentina
dc.contributor.authorMarcantoni, Andrea
dc.date.accessioned2025-03-20T09:51:07Z
dc.date.available2025-03-20T09:51:07Z
dc.date.issued2025
dc.departmentİzmir Bakırçay Üniversitesi
dc.description.abstractGlyphosate (Gly) is a broad-spectrum herbicide responsible for the inhibition of the enzyme 5-enolpyruvylshikimate-3-phosphate synthase known to be expressed exclusively in plants and not in animals. For decades Gly has been thought to be ineffective in mammals, including humans, until it was demonstrated that rodents treated with the Gly-based herbicide Roundup showed reduced content of neurotransmitters (e.g., serotonin, dopamine, norepinephrine, and acetylcholine), increased oxidative stress in the brain associated with anxiety and depression-like behaviors and learning and memory deficits. Despite compelling evidence pointing to a neurotoxic effect of Gly, an in-depth functional description of its effects on synaptic transmission is still lacking. To investigate the synaptic alterations dependent on Gly administration we performed whole-cell patch-clamp recordings and immunocytochemistry on mouse primary cultured hippocampal neurons. Our findings reveal that 30 min incubation of Gly at the acceptable daily intake dose severely impaired inhibitory GABAergic synapses. Further analysis pointed out that Gly decreased the number of postsynaptic GABAA receptors and reduced the amplitude of evoked inhibitory postsynaptic currents, the readily releasable pool size available for synchronous release and the quantal size. Finally, a decreased number of release sites has been observed. Consistently, morphological analyses showed that the density of both pre- and post-synaptic inhibitory compartments decorating pyramidal cell dendrites was reduced by Gly. In conclusion, our experiments define for the first time the effects induced by Gly on GABAergic synapses, and reveal that Gly significantly impairs both pre- and postsynaptic mechanisms.
dc.description.sponsorshipFSE REACT-EU Program
dc.description.sponsorshipPhD scholarship from the FSE REACT-EU Program.
dc.identifier.doi10.1016/j.neuropharm.2024.110183
dc.identifier.issn0028-3908
dc.identifier.issn1873-7064
dc.identifier.pmid39401670
dc.identifier.scopus2-s2.0-85206850161
dc.identifier.scopusqualityQ1
dc.identifier.urihttps://doi.org/10.1016/j.neuropharm.2024.110183
dc.identifier.urihttps://hdl.handle.net/20.500.14034/2432
dc.identifier.volume262
dc.identifier.wosWOS:001342330500001
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherPergamon-Elsevier Science Ltd
dc.relation.ispartofNeuropharmacology
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_WOS_20250319
dc.subjectGlyphosate
dc.subjectGABAergic synapses
dc.subjectHippocampal neurons
dc.subjectPatch-clamp
dc.subjectImmunocytochemistry
dc.subjectGephyrin
dc.titleGlyphosate impairs both structure and function of GABAergic synapses in hippocampal neurons
dc.typeArticle

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