Remodeling of hippocampal GABAergic system in adult offspring after maternal hypoxia and magnesium sulfate load: immunohistochemical study.
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.
Gerstein
M
M
Department of Developmental Molecular Genetics, Faculty of Health Sciences and, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Huleihel
M
M
Mane
R
R
Stilman
M
M
Kashtuzki
I
I
Hallak
M
M
Golan
H
H
D000818:Animals; D001930:Brain Injuries / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D064026:Calbindins; D005260:Female; D005968:Glutamate Decarboxylase / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D002534:Hypoxia, Brain / Q000150:complications / Q000503:physiopathology*; D007150:Immunohistochemistry; D008278:Magnesium Sulfate / Q000494:pharmacology*; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010320:Parvalbumins / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D064030:S100 Calcium Binding Protein G / Q000187:drug effects / Q000378:metabolism; D050495:Vesicular Inhibitory Amino Acid Transport Proteins / Q000187:drug effects / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000187:drug effects / Q000378:metabolism*
D064026:Calbindins; D018696:Neuroprotective Agents; D010320:Parvalbumins; D064030:S100 Calcium Binding Protein G; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; C492244:Viaat protein, mouse; D005680:gamma-Aminobutyric Acid; D008278:Magnesium Sulfate; D005968:Glutamate Decarboxylase