title: Effect of neurosteroids on the retinal gabaergic system and electroretinographic activity in the golden hamster.
abstract: It has been established that neurosteroids can either inhibit or enhance GABA(A) receptor activity. Although GABA is the main inhibitory neurotransmitter in the mammalian retina, the effects of neurosteroids on retinal GABAergic activity have not been investigated. The aim of this work was to study the neurochemical and electroretinographic effects of neurosteroids in the golden hamster. On one hand, pregnenolone sulfate inhibited and allotetrahydrodeoxycorticosterone increased GABA-induced [36Cl]- uptake in neurosynaptosomes. On the other hand, in whole retinas, pregnenolone sulfate increased, whereas allotetrahydrodeoxycorticosterone decreased high potassium-induced [3H]GABA release. The effect of both neurosteroids on GABA release was Ca2+-dependent, as in its absence release was not altered. The intravitreal injection of pregnenolone sulfate or vigabatrin (an irreversible inhibitor of GABA degradation) significantly decreased scotopic b-wave amplitude, whereas the opposite effect was evident when bicuculline or allotetrahydrodeoxycorticosterone were injected. A protein with a molecular weight close to that of hamster adrenal cytochrome P450 side-chain cleavage (P450scc) was detected in the hamster retina. P450scc-like immunoreactivity was localized in the inner nuclear and the ganglion cell layers. These results indicate that neurosteroids significantly modulate retinal GABAergic neurotransmission and electroretinographic activity. In addition, the selective localization of P450scc suggests that neurosteroid biosynthesis might occur only in some layers of the hamster retina.
authors: Laboratorio de Neuroquímica Retiniana y Oftalmología Experimental, Departamento de Bioqu'mica Humana, Facultad de Medicina, Universidad de Buenos Aires, Conicet, Buenos Aires, Argentina.
authors: Carolina O
authors: CO
authors: Jaliffa
authors: Sarah
authors: S
authors: Howard
authors: Esteban
authors: E
authors: Hoijman
authors: Ezequiel
authors: E
authors: Salido
authors: María I Keller
authors: MI
authors: Sarmiento
authors: Pablo
authors: P
authors: Arias
authors: Ruth E
authors: RE
authors: Rosenstein
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D003345:Corticosterone / Q000031:analogs & derivatives / Q000494:pharmacology; D006224:Cricetinae; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004596:Electroretinography / Q000187:drug effects; D018756:GABA Antagonists / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008647:Mesocricetus; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D011284:Pregnenolone / Q000378:metabolism / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D012160:Retina / Q000187:drug effects / Q000378:metabolism*; D013256:Steroids / Q000096:biosynthesis* / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D020888:Vigabatrin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D000927:Anticonvulsants; D018756:GABA Antagonists; D013256:Steroids; D005680:gamma-Aminobutyric Acid; C003676:tetrahydrocorticosterone; D011284:Pregnenolone; D003577:Cytochrome P-450 Enzyme System; D020888:Vigabatrin; D003345:Corticosterone