Related Experiment Video
Updated: Apr 24, 2026
Modeling Encephalopathy of Prematurity Using Prenatal Hypoxia-ischemia with Intra-amniotic Lipopolysaccharide in Rats
Published on: November 20, 2015
Tiagabine improves hippocampal long-term depression in rat pups subjected to prenatal inflammation
Aline Rideau Batista Novais1, Nadine Crouzin2, Mélanie Cavalier3
1Laboratory 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.
Insights
Maternal inflammation during pregnancy in rats, caused by lipopolysaccharide (LPS), impairs brain development. This leads to deficits in GABAergic interneurons and synaptic plasticity, potentially contributing to cognitive and behavioral issues in offspring.
Area of Science:
- Neuroscience
- Developmental Neuroscience
- Neuroinflammation
Background:
- Maternal inflammation during pregnancy is linked to offspring neurodevelopmental disorders.
- Hippocampal synaptic plasticity, including long-term potentiation (LTP) and long-term depression (LTD), is crucial for cognitive functions.
- Prenatal inflammation models offer insights into the mechanisms underlying these disorders.
Purpose of the Study:
- To investigate the impact of prenatal maternal inflammation induced by lipopolysaccharide (LPS) on hippocampal GABAergic system function and synaptic plasticity in male rat offspring.
- To explore the role of GABAergic transmission deficits in the observed neurodevelopmental alterations.
- To assess the therapeutic potential of modulating GABAergic tone.
Main Methods:
- Sprague Dawley rats were exposed to LPS or saline on gestational day 19.
- Hippocampal tissues from male offspring (postnatal days 12-25) were analyzed morphologically and functionally.
- Electrophysiological recordings were used to assess LTP and LTD.
- The effect of tiagabine, a GABA reuptake inhibitor, was evaluated.
Main Results:
- Prenatal LPS exposure resulted in a deficit of hippocampal GABAergic interneurons and impaired presynaptic GABAergic transmission in male offspring.
- LPS exposure led to premature loss of LTD and aberrant LTP.
- Tiagabine treatment prevented the impairment of LTD and aberrant LTP in LPS-exposed offspring, indicating the central role of GABA deficiency.
Conclusions:
- Prenatal LPS-induced maternal inflammation disrupts hippocampal GABAergic function and synaptic plasticity in juvenile male rats.
- GABAergic system deficits are central to the observed dysregulation of synaptic plasticity.
- Modulating GABAergic tone represents a potential therapeutic strategy for neurodevelopmental impairments stemming from 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.
