title: Tiagabine improves hippocampal long-term depression in rat pups subjected to prenatal inflammation.
abstract: Maternal inflammation during pregnancy is associated with the later development of cognitive and behavioral impairment in the offspring, reminiscent of the traits of schizophrenia or autism spectrum disorders. Hippocampal long-term potentiation and long-term depression of glutamatergic synapses are respectively involved in memory formation and consolidation. In male rats, maternal inflammation with lipopolysaccharide (LPS) led to a premature loss of long-term depression, occurring between 12 and 25 postnatal days instead of after the first postnatal month, and aberrant occurrence of long-term potentiation. We hypothesized this would be related to GABAergic system impairment. Sprague Dawley rats received either LPS or isotonic saline ip on gestational day 19. Male offspring's hippocampus was studied between 12 and 25 postnatal days. Morphological and functional analyses demonstrated that prenatal LPS triggered a deficit of hippocampal GABAergic interneurons, associated with presynaptic GABAergic transmission deficiency in male offspring. Increasing ambient GABA by impairing GABA reuptake with tiagabine did not interact with the low frequency-induced long-term depression in control animals but fully prevented its impairment in male offspring of LPS-challenged dams. Tiagabine furthermore prevented the aberrant occurrence of paired-pulse triggered long-term potentiation in these rats. Deficiency in GABA seems to be central to the dysregulation of synaptic plasticity observed in juvenile in utero LPS-challenged rats. Modulating GABAergic tone may be a possible therapeutic strategy at this developmental stage.
authors.affiliation: Laboratory IBMM-UMR 5247 "Institut des Biomolécules Max Mousseron", CNRS - Montpellier 1 University - Montpellier 2 University, Montpellier, France; Neonatal Intensive Care Unit, Montpellier University Hospital, Montpellier, France.
authors.forename: Aline
authors.initials: A
authors.lastname: Rideau Batista Novais
authors.affiliation: Laboratory NICN-UMR7259 "Neurobiologie des Interactions Cellulaires et Neurophysiopathologie", CNRS - Aix-Marseille University, Marseille, France.
authors.forename: Nadine
authors.initials: N
authors.lastname: Crouzin
authors.affiliation: Laboratory IBMM-UMR 5247 "Institut des Biomolécules Max Mousseron", CNRS - Montpellier 1 University - Montpellier 2 University, Montpellier, France.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Cavalier
authors.affiliation: Laboratory IBMM-UMR 5247 "Institut des Biomolécules Max Mousseron", CNRS - Montpellier 1 University - Montpellier 2 University, Montpellier, France; Neonatal Intensive Care Unit, Montpellier University Hospital, Montpellier, France.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Boubal
authors.affiliation: Laboratory IBMM-UMR 5247 "Institut des Biomolécules Max Mousseron", CNRS - Montpellier 1 University - Montpellier 2 University, Montpellier, France.
authors.forename: Janique
authors.initials: J
authors.lastname: Guiramand
authors.affiliation: Laboratory IBMM-UMR 5247 "Institut des Biomolécules Max Mousseron", CNRS - Montpellier 1 University - Montpellier 2 University, Montpellier, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Cohen-Solal
authors.affiliation: Laboratory IBMM-UMR 5247 "Institut des Biomolécules Max Mousseron", CNRS - Montpellier 1 University - Montpellier 2 University, Montpellier, France.
authors.forename: Marie-Céleste
authors.initials: MC
authors.lastname: de Jesus Ferreira
authors.affiliation: Laboratory IBMM-UMR 5247 "Institut des Biomolécules Max Mousseron", CNRS - Montpellier 1 University - Montpellier 2 University, Montpellier, France; Neonatal Intensive Care Unit, Montpellier University Hospital, Montpellier, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Cambonie
authors.affiliation: Laboratory IBMM-UMR 5247 "Institut des Biomolécules Max Mousseron", CNRS - Montpellier 1 University - Montpellier 2 University, Montpellier, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Vignes
authors.affiliation: Laboratory IBMM-UMR 5247 "Institut des Biomolécules Max Mousseron", CNRS - Montpellier 1 University - Montpellier 2 University, Montpellier, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Barbanel
mesh_terms: D000818:Animals; D002659:Child Development Disorders, Pervasive / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D005260:Female; D059330:GABAergic Neurons / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D009473:Neuronal Plasticity; D009557:Nipecotic Acids / Q000008:administration & dosage*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000078308:Tiagabine; D005680:gamma-Aminobutyric Acid / Q000187:drug effects / Q000378:metabolism*
chemical_list: D008070:Lipopolysaccharides; D009557:Nipecotic Acids; D005680:gamma-Aminobutyric Acid; D000078308:Tiagabine