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Modificazioni nella funzionalità , nell'espressione dei recettori GABAA extrasinaptici e nella plasticità sinaptica nell'ippocampo di ratto durante la gravidanza e dopo il parto.

Murru, Luca (2009) Modificazioni nella funzionalità , nell'espressione dei recettori GABAA extrasinaptici e nella plasticità sinaptica nell'ippocampo di ratto durante la gravidanza e dopo il parto. [Doctoral Thesis]

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Abstract

Pregnancy is associated with changes in mood and anxiety level as well as with marked hormonal fluctuations. Increases in the brain concentrations of neuroactive steroids during pregnancy in rats are accompanied by changes in expression of subunits of the GABA type A receptor (GABAA-R) in the brain. Granule cells of the dentate gyrus (DGGCs) exhibit two components of inhibitory GABAergic transmission: a phasic component mediated by synapticGABAA-Rs, and a tonic component mediated by extrasynapticGABAA-Rs. Recordings of GABAergic currents were obtained from hippocampal slices prepared from rats in estrus, at pregnancy day 15 (P15) or P19, or at 2 d after delivery. Exogenous GABA or 3_,5_-THP induced an increase in tonic current in DGGCs that was significantly greater at P19 than in estrus. Neither tonic nor phasic currents were affected by pregnancy in CA1 pyramidal cells. Immunohistochemical analysis revealed a marked increase in the abundance of the _ subunit of the GABAA-R and a concomitant decrease in that of the _2 subunit in the hippocampus at P19. Expression of the_4 subunit did not change during pregnancy but was increased 2 d after delivery. Treatment of rats from P12 to P18 with the 5_-reductase inhibitor finasteride prevented the changes in tonic current and in _ and _2 subunit expression normally apparent at P19. These data suggest that the number of extrasynaptic GABAA-Rs is increased in DGGCs during late pregnancy as a consequence of the associated marked fluctuations in the brain levels of neuroactive steroids.

Item Type:Doctoral Thesis
Date:January 2009
Tutor:Biggio, Giovanni
PhD classes:Ciclo 21 > Neuroscienze
Coordinator:Fratta, Walter
Institution:Universita' degli Studi di Cagliari
Divisions:Dipartimenti (fino a dicembre 2011) > Dipartimento di Biologia sperimentale
Subjects:Area 05 - Scienze biologiche > BIO/14 Farmacologia
Uncontrolled Keywords:GABAA receptor _ subunit; pregnancy; delivery; 3_-hydroxy-5_-pregnan-20-one; dentate gyrus granule cells; tonic current
ID Code:471
Deposited On:11 Dec 2009 11:04

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