Plastic neuronal changes in GABA(A) receptor gene expression induced by progesterone metabolites: in vitro molecular and functional studies.
Expression of specific gamma-aminobutyric acid type A (GABA(A)) receptor subunit genes in neurons is affected by endogenous modulators of receptor function such as neuroactive steroids. Neuroactive steroids such as the progesterone metabolite allopregnanolone might thus exert differential effects on GABA(A) receptor plasticity in neurons, likely accounting for some of the physiological actions of these compounds. Here we summarise experimental data obtained in vitro that show how fluctuations in the concentration of progesterone regulate both the expression and function of GABA(A) receptors. The data described in this manuscript are in agreement with the notion that fluctuations in the concentrations of progesterone and its metabolite allopregnanolone play a major role in the temporal pattern of expression of various subunits of the GABA(A) receptor. Thus, rapid and long-lasting increases or decreases in the concentrations of these steroid derivatives observed in physiological and patho-physiological conditions, or induced by pharmacological treatments, might elicit selective changes in GABA(A) receptor gene expression and function in specific neuronal populations. Given both the importance of GABA(A) receptors in the regulation of neuronal excitability and the large fluctuations in the plasma and brain concentrations of neuroactive steroids associated with physiological conditions and the response to environmental stimuli, these compounds are likely among the most relevant endogenous modulators that could affect emotional and affective behaviors.
Biggio
Francesca
F
Department of Experimental Biology, Section of Neuroscience, University of Cagliari, Cagliari, Italy.
Gorini
Giorgio
G
Caria
Stefania
S
Murru
Luca
L
Mostallino
Maria Cristina
MC
Sanna
Enrico
E
Follesa
Paolo
P
D000818:Animals; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000502:physiology; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D003900:Desoxycorticosterone / Q000031:analogs & derivatives / Q000494:pharmacology; D004594:Electrophysiology; D005455:Fluorescent Antibody Technique; D015870:Gene Expression / Q000187:drug effects; D009473:Neuronal Plasticity / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D011280:Pregnanolone / Q000494:pharmacology; D011374:Progesterone / Q000009:adverse effects / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000302:isolation & purification; D051381:Rats; D011963:Receptors, GABA-A / Q000096:biosynthesis* / Q000235:genetics*; D013375:Substance Withdrawal Syndrome / Q000378:metabolism
D018076:DNA, Complementary; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D003900:Desoxycorticosterone; C009413:tetrahydrodeoxycorticosterone; D011374:Progesterone; D011280:Pregnanolone