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Biomedical subjects

Frédéric Bancel

Publications and source records attributed to Frédéric Bancel.

4 recordsLinked to original sources
PubMed2006

Rapid inhibition of Ca2+ influx by neurosteroids in murine embryonic sensory neurones.

The non-genomic role of neuroactive steroids on [Ca2+]i transients induced by GABA receptor activation was investigated in cultured dorsal root ganglia (DRG) neurones at embryonic stage E13. [Ca2+]i measurements were performed with Fura-2 fast fluorescence microfluorimetry. Application of the GABAA receptor agonist muscimol (Musci) evoked an increase in [Ca2+]i, confirming the excitatory effect of GABA at this embryonic stage. The muscimol-induced [Ca2+]i response was inhibited by progesterone (Proges) and its primary metabolite allopregnanolone (Allo) in a rapid, reversible and dose-dependent manner. These calcium transients were suppressed in the absence of external Ca2+ or in the presence of Ni2+ + Cd2+ suggesting an involvement of voltage-activated Ca2+ channels. In contrast, none of these steroids affected the resting [Ca2+]i nor exhibited any inhibitory effect on 50 mM KCl-induced [Ca2+]i increases. In view of the well-established potentiation of GABAA receptor by direct binding of neurosteroids, the inhibitory effects described in this study seem to involve distinct mechanisms. This new inhibitory effect of progesterone is observed at low and physiological concentrations, is rapid and independent of RU38486, an antagonist of the classic progesterone receptor, probably involving a membrane receptor. Using RT-PCR, we demonstrated the expression of progesterone receptor membrane component 1 (Pgrmc1), encoding 25-Dx, a membrane-associated progesterone binding protein in DRG neurones at different stages of development. In conclusion, we describe for the first time a rapid effect of progestins on embryonic DRG neurones involving an antagonistic effect of progesterone and allopregnanolone on GABAA receptors.

Animals↗
PubMed2005

Intracellular Ca2+ regulation in rat motoneurons during development.

Changes in intracellular Ca(2+) concentration ([Ca(2+)](i)) control the setting up of the neuro-muscular synapse in vitro and probably in vivo. Dissociated cultures of purified embryonic (E15) rat motoneurons were used to explore the molecular mechanisms by which endoplasmic reticulum Ca(2+) stores, via both ryanodine-sensitive and IP(3)-sensitive intracellular Ca(2+) channels control [Ca(2+)](i) homeostasis in these neurons during ontogenesis. Fura-2 microspectrofluorimetry monitorings in single neurons showed that caffeine-induced responses of [Ca(2+)](i) increased progressively from days 1-7 in culture. These responses were blocked by ryanodine and nicardipine but not by omega-conotoxin-GVIA or omega-conotoxin-MVIIC suggesting a close functional relationship between ryanodine-sensitive and L-type Ca(v)1 Ca(2+) channels. Moreover, after 6 days in vitro, neurons exhibited spontaneous or caffeine-induced Ca(2+) oscillations that were attenuated by nicardipine. In 1-day-old neurons, both thapsigargin or CPA, which deplete Ca(2+) stores from the endoplasmic reticulum, induced an increase in [Ca(2+)](i) in 75% of the neurons tested. The number of responding motoneurons declined to 25% at 5-6 days in vitro. Xestospongin-C, a membrane-permeable IP(3) receptor inhibitor blocked the CPA-induced [Ca(2+)](i) response in all stages. RT-PCR studies investigating the expression pattern of RYR and IP(3) Ca(2+) channels isoforms confirmed the presence of their different isoforms and provided evidence for a specific pattern of development for RYR channels during the first week in vitro. Taken together, present results show that the control of motoneuronal [Ca(2+)](i) homeostasis is developmentally regulated and suggest the presence of an intracellular ryanodine-sensitive Ca(2+) channel responsible for a Ca(2+)-induced Ca(2+) release in embryonic motoneurons following voltage-dependent Ca(2+) entry via L-type Ca(2+) channels.

Animals↗
PubMed2003

Neurosteroid regulation of oxytocin and vasopressin release from the rat supraoptic nucleus.

In adult rats somato-dendritic release of oxytocin and vasopressin from magnocellular neurones in the supraoptic nucleus of the hypothalamus has important autoregulatory actions on the neuronal electrical activity, and in neonatal rats it plays a role in the development of dendritic arborisation. In the adult, oxytocin effects are modulated by allopregnanolone via an interaction with inhibitory GABAA receptors. This study examined the effects of allopregnanolone, progesterone and 17beta-oestradiol on oxytocin and vasopressin release from intact isolated supraoptic nuclei and from the neurophypophyses in rats of differing ages. In supraoptic nuclei from rats of 3-4 weeks old or less, all three neurosteroids induced oxytocin release from the isolated supraoptic nucleus, but only allopregnanolone induced significant release of vasopressin. Surprisingly, in these very young rats, allopregnanolone-induced oxytocin release was inhibited by GABAA receptor antagonists as well as by an oxytocin receptor antagonist. By contrast, in supraoptic nuclei from adult rats allopregnanolone-induced oxytocin release was much smaller, and was enhanced in the presence of bicuculline. The GABAA receptor agonist muscimol also induced oxytocin release from supraoptic nuclei in young rats, but had no effect in adult rats. Oxytocin cells isolated from young rats showed an increase in [Ca2+]i in response to both allopregnanolone and muscimol. Allopregnanolone had no effect on [Ca2+]i or on the release of oxytocin or vasopressin from neurohypophysial axon terminals in either young or old rats. We conclude that, in very young rats, (i) neurosteroids induce oxytocin release from the supraoptic nucleus by a mechanism that partly depends on the presence of GABA, which in young rats is depolarising to oxytocin cells, and which also partly depends upon endogenous oxytocin, and (ii) the effect of allopregnanolone upon oxytocin release changes with age, as the functional activity of GABAA receptors changes from excitation to inhibition of oxytocin cells.

Aging↗