title: Gestational Hypothyroxinemia Affects Glutamatergic Synaptic Protein Distribution and Neuronal Plasticity Through Neuron-Astrocyte Interplay.
abstract: Gestational hypothyroxinemia, characterized by low levels of maternal thyroxine (T4) during gestation, is closely associated with cognitive impairment in offspring. Studies in animal models have shown that this condition alters neuronal glutamatergic synapses in the hippocampus. Given that astrocytes critically contribute to the establishment and functioning of synapses, the aim of this study was to determine the effects of gestational hypothyroxinemia on the capacity of astrocytes to regulate glutamatergic synapses. In an in vitro co-culture model of astrocytes and hippocampal neurons, gestational hypothyroxinemia profoundly affected the synaptic patterns of GluN1 and CD3ζ in an astrocyte-dependent manner. These effects were associated with impaired plasticity that was dependent on both neuronal and astrocyte contributions. These results highlight the importance of neuron-astrocyte interplay in the deleterious effects of gestational hypothyroxinemia and the timely diagnosis and treatment of this condition during gestation to ensure proper central nervous system development in offspring.
authors.affiliation: Millennium Institute on Immunology and Immunotherapy, Departamento de Ciencias Biológicas, Facultad de Ciencias Biológicas y Facultad de Medicina, Universidad Andrés Bello, Santiago, Chile.
authors.forename: Pablo
authors.initials: P
authors.lastname: Cisternas
authors.affiliation: INSERM Unité Mixte de Recherche 1064, Institut Transplantation Urologie Nephrologie, Centre Hospitalier Universitaire Nantes, Nantes, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Louveau
authors.affiliation: INSERM Unité Mixte de Recherche 1064, Institut Transplantation Urologie Nephrologie, Centre Hospitalier Universitaire Nantes, Nantes, France.|Millennium Institute on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Bueno
authors.affiliation: INSERM Unité Mixte de Recherche 1064, Institut Transplantation Urologie Nephrologie, Centre Hospitalier Universitaire Nantes, Nantes, France.|Millennium Institute on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.|Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Alexis M
authors.initials: AM
authors.lastname: Kalergis
authors.affiliation: INSERM Unité Mixte de Recherche 1064, Institut Transplantation Urologie Nephrologie, Centre Hospitalier Universitaire Nantes, Nantes, France. helene.boudin@univ-nantes.fr.|INSERM Unité de Recherche 913, L'Institut des Maladies de l'Appareil Digestif, Université de Nantes, 44035, Nantes, France. helene.boudin@univ-nantes.fr.
authors.forename: Hélène
authors.initials: H
authors.lastname: Boudin
authors.affiliation: Millennium Institute on Immunology and Immunotherapy, Departamento de Ciencias Biológicas, Facultad de Ciencias Biológicas y Facultad de Medicina, Universidad Andrés Bello, Santiago, Chile. claudia.riedel@unab.cl.
authors.forename: Claudia A
authors.initials: CA
authors.lastname: Riedel
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D002450:Cell Communication / Q000187:drug effects; D002452:Cell Count; D018920:Coculture Techniques; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005971:Glutamates / Q000378:metabolism*; D005998:Glycine / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D021381:Protein Transport / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D013974:Thyroxine / Q000097:blood*
chemical_list: D005971:Glutamates; D009419:Nerve Tissue Proteins; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D013974:Thyroxine; D005998:Glycine
keywords: Astrocyte; Gestational hypothyroxinemia; Glutamatergic synapse; Neuron