Changes in expression and function of extrasynaptic GABAA receptors in the rat hippocampus during pregnancy and after delivery
Journal of Neuroscience. 2009-02-11; 29(6): 1755-1765
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1. J Neurosci. 2009 Feb 11;29(6):1755-65. doi: 10.1523/JNEUROSCI.3684-08.2009.
Changes in expression and function of extrasynaptic GABAA receptors in the rat
hippocampus during pregnancy and after delivery.
Sanna E(1), Mostallino MC, Murru L, Carta M, Talani G, Zucca S, Mura ML, Maciocco
E, Biggio G.
(1)Department of Experimental Biology, Section of Neuroscience, University of
Cagliari, and National Research Council, Institute of Neuroscience, 09123
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 (GABA(A)-R) in the brain.
Granule cells of the dentate gyrus (DGGCs) exhibit two components of inhibitory
GABAergic transmission: a phasic component mediated by synaptic GABA(A)-Rs, and a
tonic component mediated by extrasynaptic GABA(A)-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
3alpha,5alpha-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 delta subunit of the GABA(A)-R
and a concomitant decrease in that of the gamma(2) subunit in the hippocampus at
P19. Expression of the alpha(4) subunit did not change during pregnancy but was
increased 2 d after delivery. Treatment of rats from P12 to P18 with the
5alpha-reductase inhibitor finasteride prevented the changes in tonic current and
in delta and gamma(2) subunit expression normally apparent at P19. These data
suggest that the number of extrasynaptic GABA(A)-Rs is increased in DGGCs during
late pregnancy as a consequence of the associated marked fluctuations in the
brain levels of neuroactive steroids.
PMID: 19211882 [Indexed for MEDLINE]