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Modeling Encephalopathy of Prematurity Using Prenatal Hypoxia-ischemia with Intra-amniotic Lipopolysaccharide in Rats
Published on: November 20, 2015
[DYNAMICS OF GLUTAMINE SYNTHASE ACTIVITY IN RAT BRAIN IN PRENATAL HYPOXIA MODEL]
Insights
Prenatal hypoxia during embryonic development significantly alters glutamine synthetase activity in rat offspring brains, impacting glutamate metabolism. These changes are most pronounced in the cerebral cortex and cerebellum, especially in younger animals.
Area of Science:
- Neuroscience
- Developmental Biology
- Biochemistry
Background:
- Prenatal ontogenesis is highly sensitive to stressors like hypoxia.
- Hypoxia can cause pathological changes in the central nervous system.
- Glutamate excitotoxicity and apoptosis are linked to hypoxia-induced anaerobic glycolysis.
Purpose of the Study:
- To investigate the impact of prenatal hypoxia on glutamine synthetase activity in rat offspring.
- To determine how hypoxia at different prenatal stages affects glutamate metabolism.
- To assess the long-term effects of prenatal stress on brain enzyme activity.
Main Methods:
- Pregnant rats were exposed to hypoxia (5% O2, 95% N2) for 30 minutes daily during specific prenatal periods (organogenesis, fetal).
- Offspring were assessed at 1 and 3 months of age for glutamine synthetase activity.
- Enzyme activity was measured in various brain regions, including the cerebral cortex and cerebellum.
Main Results:
- Prenatal hypoxia during embryonic organogenesis led to significant changes in glutamine synthetase activity.
- These changes were most pronounced in the cerebral cortex and cerebellum compared to other hypoxia exposure times.
- Enzyme activity was lower in 1-month-old offspring than in 3-month-old offspring, indicating a lasting effect.
Conclusions:
- Stress during critical brain development periods, like organogenesis, disrupts glutamate metabolism.
- Prenatal hypoxia affects glutamine synthetase, a key enzyme in glutamate regulation.
- The timing and duration of prenatal hypoxia influence the severity of neurochemical alterations in offspring.
Abstract:
Prenatal ontogenesis is a period of high sensitivity to stressful impact, so any stressor can lead to changes of physiological, biochemical indicators, behavioral and cognitive functions. The most common and clinically significant stress factor, which the embryo may be exposed during embryonic development, is hypoxia. In this case pathological changes in the central nervous system depend on the duration and severity of hypoxic exposure, individual tolerance and the stage of prenatal development, at each of which in the brain take place the basic histogenetic processes. By activating energetically disadvantageous anaerobic glycolysis hypoxia leads to excess of glutamate emission and cell apoptosis. Glutamine synthase is a basic enzyme that regulates metabolism of glutamate, catalyzing conversion of glutamate to glutamine with ammonia detoxification. The aim of the presented work was to reveal changes in the activity of one of the key enzyme of glutamate metabolism- glutamine synthetase in the brain of offspring of white rats undergone to hypoxia at different stages of prenatal ontogenesis. Hypoxia was created by placing female rats at stages of the pregnancy, corresponding to progestation period of organogenesis and fetal period of prenatal development, in the hypobaric chamber with exposure to 5% oxygen and 95% nitrogen gas mixture during 30 minutes per day. The offspring obtained from females of control and experimental groups were used for biochemical determinations in the age of 1 and 3 month. It has been established that hypoxia exposed to pregnant females during embryonic organogenesis causes significant changes in enzyme activity, particularly pronounced in the cerebral cortex and cerebellum, as compared with progestational and fetal hypoxia. Enzyme activity decreased in a greater degree in one-month-old rats undergone to prenatal hypoxia, than three- month-old animals. Thus, stress during intensive processes of proliferation and migration of cells of the forming brain violates glutamate metabolism of the brain.
