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Modeling Encephalopathy of Prematurity Using Prenatal Hypoxia-ischemia with Intra-amniotic Lipopolysaccharide in Rats
Published on: November 20, 2015
Prenatal exposure to lipopolysaccharide results in cognitive deficits in age-increasing offspring rats
1Department of Pharmaceutics, Institute of Materia Medica, College of Pharmacy, Third Military Medical University, Chongqing 400038, PR China.
Insights
Maternal inflammation during pregnancy, caused by lipopolysaccharide (LPS), impairs spatial learning and memory in rat offspring long-term. This neurodevelopmental brain damage worsens with age, affecting synaptic function and increasing vulnerability.
Area of Science:
- Neuroscience
- Developmental Biology
- Toxicology
Background:
- Maternal infection and inflammation are potential risk factors for neurodevelopmental brain damage in offspring.
- Prenatal exposure to inflammatory stimuli may have lasting effects on brain structure and function.
Purpose of the Study:
- To investigate the long-term effects of prenatal exposure to low-level lipopolysaccharide (LPS)-induced inflammation on spatial learning and memory in rat offspring.
- To examine the impact of maternal inflammation on hippocampal CA1 region structure and molecular markers of neuronal and glial function.
Main Methods:
- Pregnant Sprague-Dawley rats were exposed to LPS or saline during gestation.
- Offspring were tested for spatial learning and memory using the Morris water maze at young, adult, and aged stages.
- Hippocampal CA1 region was analyzed for neuronal loss, synaptophysin (SYP), and glial fibrillary acidic protein (GFAP) expression.
Main Results:
- LPS-exposed offspring exhibited impaired spatial learning and memory, characterized by longer escape latencies and path lengths.
- Histological analysis revealed significant neuron loss, decreased SYP expression, and increased GFAP expression in the hippocampal CA1 region of LPS-exposed offspring.
- These deficits and alterations were more pronounced with increasing age.
Conclusions:
- Maternal systemic inflammation during pregnancy can induce long-lasting alterations in astrocyte function in offspring.
- These changes negatively impact neuronal and synapse development, increasing vulnerability to environmental factors and leading to cognitive impairment, particularly with aging.
Abstract:
Studies have suggested that maternal infection/inflammation maybe a major risk factor for neurodevelopmental brain damage. In the present study, we evaluated the effects of prenatal exposure to a low level of inflammatory stimulation lipopolysaccharide (LPS) repeatedly on spatial learning and memory performances in rat offspring's lifetime. Sixteen pregnant Sprague-Dawley rats were randomly divided into two groups. The rats in the LPS group were treated i.p. with LPS (0.79 mg/kg) at gestation day 8, 10 and 12; meanwhile the rats in the control group were treated with saline. After delivery, the rat offspring at 3- (young), 10- (adult) and 20-mon-old (aged) were allocated. Spatial learning and memory abilities were tested by Morris water maze. The structure of hippocampal CA1 region was observed by light microscopy. The expression of synaptophysin (SYP) and glial fibrillary acidic protein (GFAP) in hippocampal CA1 region were measured by immunohistochemistry. Results showed that the rat offspring of LPS group needed longer escape latency and path-length in the Morris water maze and presented a significant neuron loss, decreased expression of SYP, increased expression of GFAP in CA1 region in histological studies. All these changes were more significant with the age increasing. These findings support the hypothesis that maternal systemic inflammation may alter the state of astrocytes in rat offspring for a long time, the alteration may affect neurons and synapse development in neural system, increase the neurons' vulnerability to environment especially as the age increasing, at last result in distinct learning and memory impairment.
