ABSTRACT
Intrauterine inflammation is a major risk for offspring neurodevelopmental brain damage and may result in cognitive limitations and poor cognitive and perceptual outcomes. In the present study we tested the possibility that prenatal exposure to a high level of inflammatory factors may increase the risk for neurodegeneration in aging. The effect of systemic maternal inflammation (MI), induced by lipopolysaccharide (LPS) on offspring brain aging, was examined in 8 month old (adult) and 20 month old (aged) offspring mice. A significant effect of age was found in the distance and velocity of exploration in the open field in both groups. In addition, MI aged offspring covered longer distances and enter frequently to the center of the field compared with the aged control group. Although only little difference was found in the aged MI offspring compared with the control offspring, the overall profile of behavior of these mice differs from that of the control group, as detected by clustering analysis. The expression of the death-associated protein FAS-ligand and the amount of apoptotic cell death were examined in the brains of aged offspring. Similar levels of FAS-ligand expression and parallel density of apoptotic cells were detected in the brains of aged mice of control and MI groups. Altogether, moderate systemic MI was not found to increase the risk for cell death in the aged offspring; limited effect was found in mice profile of behavior.
Subject(s)
Aging/physiology , Inflammation/metabolism , Prenatal Exposure Delayed Effects , Age Factors , Aging/drug effects , Analysis of Variance , Animals , Animals, Newborn , Behavior, Animal , Brain/drug effects , Brain/growth & development , Brain/pathology , Cell Death/physiology , Cytokines/metabolism , Exploratory Behavior , Fas Ligand Protein/metabolism , Female , Gestational Age , Immunohistochemistry/methods , Inflammation/chemically induced , Inflammation/pathology , Learning/physiology , Lipopolysaccharides/toxicity , Mice , Motor Activity/drug effects , Motor Activity/physiology , Pregnancy , Pregnancy ComplicationsABSTRACT
A strong relationship between hypoxia and fetal brain damage has been described. Specific susceptibility of the GABAergic neurons to these conditions may be crucial to the damage induced. We have previously shown, in a mouse model, that maternal pretreatment with magnesium sulfate (Mg) partially prevented the behavioral consequences of maternal hypoxia in the adult offspring. Here, we tested the effect of maternal hypoxia and maternal Mg load on the GABAergic system of 8-month-old offspring. The immunoreactivity (IR) of several proteins expressed in GABAergic neurons and inhibitory synapses was analyzed in the following regions of the adult offspring brain: hippocampus, cortical M1, caudate putamen, and lateral globus pallidus. Maternal hypoxia reduced the density of parvalbumin (PV)-IR neurons in the hippocampus. The density of PV-IR and calbindin (CB)-IR neurons was also reduced in the deep and superficial layers of the M1. Maternal pretreatment with Mg had a prophylactic action in the superficial, but not the deep, layers of M1. Also, in offspring from the maternal hypoxia group, the vesicular GABA transporter (VGAT)-IR was enhanced in the hippocampal CA1 and hilus regions. No effect of maternal hypoxia on VGAT-IR was observed in the M1. However, maternal pretreatment with Mg enhanced VGAT-IR and glutamate decarboxylase-IR in the deep layers of the M1. In the globus pallidus, maternal hypoxia enhanced CB-IR, which was prevented by maternal pretreatment with Mg. In conclusion, maternal hypoxia induced a loss of PV-IR and CB-IR neurons; maternal pretreatment with Mg partially protected these neuron populations. An increase in proteins of inhibitory synapses, observed under hypoxic conditions in several brain regions, may be a result of some compensatory mechanism.
