Tiagabine improves hippocampal long-term depression in rat pups subjected to prenatal inflammation

Aline Rideau Batista Novais (1) , Nadine Crouzin (2) , Mélanie Cavalier (1) , Mathilde Boubal , Janique Guiramand (1) , Catherine Cohen-Solal (1) , Marie-Céleste de Jesus Ferreira (1) , Gilles Cambonie (3) , Michel Vignes (1) , Gérard Barbanel (1)

1 IBMM - Institut des Biomolécules Max Mousseron [Pôle Chimie Balard]
2 NICN - Neurobiologie des interactions cellulaires et neurophysiopathologie - NICN
3 Service de Néonatalogie

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.

Mots clés: Gamma-aminobutyric acid; Neurons; Long-term potentiation; Hippocampus; Synaptic plasticity; Electrophysiology; Graphs; Inflammation

Domaines: Neurosciences [q-bio.NC]

Aline Rideau Batista Novais, Nadine Crouzin, Mélanie Cavalier, Mathilde Boubal, Janique Guiramand, et al.. Tiagabine improves hippocampal long-term depression in rat pups subjected to prenatal inflammation. PLoS ONE, 2014, 9 (9), pp.e106302. ⟨10.1371/journal.pone.0106302⟩. ⟨hal-01078790⟩