title: Acute hypoxic hypoxia transiently reduces GABA(A) binding site number in developing chick optic lobe.
abstract: The Central Nervous System is known to be critically affected in the prenatal-perinatal period by hypoxic-ischemic insults, which produce several disorders such as loss of neural projections, increased susceptibility to seizures, apoptosis and an imbalance in normal activity of glutamatergic and GABAergic neurones, resulting in acute cell excitotoxicity. The aim of the present work was to establish a chick embryo model of normobaric acute hypoxic hypoxia as well as to evaluate modifications in GABA(A) receptor complex from chick optic lobe, that may result from this injury. Fertile chicken (Gallus gallus domesticus) eggs from White Leghorn were incubated and at embryonic days (ED) 12 to 18, subjected to a stream of 8%O(2)/92%N(2) during1 h, and then were either returned to their shelves in the incubator for recovery, or immediately processed for biochemical studies. Hypoxic treatment produced a significant age dependent reduction in GABA binding sites showing the greatest decrease at the earliest stages studied (ED12-ED16). Saturation curves of GABA binding performed at ED12 showed a decrease in B(max), (control, 5.48+/-0.20, hypoxic, 3.90+/-0.39 pmol/mg protein), but no significant change in K(d). Following 48 h in normoxic atmosphere post-hypoxia reduction in [3H]GABA binding was reversed. Pharmacological properties of GABA(A) receptor at ED12 showed that positive allosteric modulation effects of the steroid 3alpha-hydroxy-5alpha-pregnan-20-one and the barbiturate pentobarbital sodium were enhanced by the treatment. This model of acute prenatal hypoxic hypoxia produced marked alterations in inhibitory CNS neurotransmission that proved reversible and age dependent.
authors: Instituto de Biología Celular y Neurociencias, Prof. E. De Robertis, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, 1121, Buenos Aires, Argentina.
authors: D J
authors: DJ
authors: Rodríguez Gil
authors: M S
authors: MS
authors: Viapiano
authors: S
authors: S
authors: Fiszer de Plazas
mesh_terms: D000208:Acute Disease; D000494:Allosteric Regulation; D000818:Animals; D001665:Binding Sites; D002642:Chick Embryo; D018757:GABA Modulators / Q000494:pharmacology; D000860:Hypoxia / Q000196:embryology* / Q000378:metabolism*; D009899:Optic Lobe, Nonmammalian / Q000196:embryology* / Q000378:metabolism; D010424:Pentobarbital / Q000494:pharmacology; D011280:Pregnanolone / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000378:metabolism*; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D018757:GABA Modulators; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D011280:Pregnanolone; D010424:Pentobarbital