Beneficial Effects of Remifentanil Against Excitotoxic Brain Damage in Newborn Mice

Background: Remifentanil, a synthetic opioid used for analgesia during cesarean sections, has been shown in ex vivo experiments to exert anti-apoptotic activity on immature mice brains. The present study aimed to characterize the impact of remifentanil on brain lesions using an in vivo model of excitotoxic neonatal brain injury.Methods: Postnatal day 2 (P2) mice received three intraperitoneal injections of remifentanil (500 ng/g over a 10-min period) or saline just before an intracortical injection of ibotenate (10 μg). Cerebral reactive oxygen species (ROS) production, cell death, in situ labeling of cortical caspase activity, astrogliosis, inflammation mediators, and lesion size were determined at various time points after ibotenate injection. Finally, behavioral tests were performed until P18.Results: In the injured neonatal brain, remifentanil significantly decreased ROS production, cortical caspase activity, DNA fragmentation, interleukin-1β levels, and reactive astrogliosis. At P7, the sizes of the ibotenate-induced lesions were significantly reduced by remifentanil treatment. Performance on negative geotaxis (P6-8) and grasping reflex (P10-12) tests was improved in the remifentanil group. At P18, a sex specificity was noticed; remifentanil-treated females spent more time in the open field center than did the controls, suggesting less anxiety in young female mice.Conclusions:In vivo exposure to remifentanil exerts a beneficial effect against excitotoxicity on the developing mouse brain, which is associated with a reduction in the size of ibotenate-induced brain lesion as well as prevention of some behavioral deficits in young mice. The long-term effect of neonatal exposure to remifentanil should be investigated

Faire lien. Aristocratie, réseaux et échanges compétitifs: Mélanges en l'honneur de Régine Le Jan

International audienceRégine Le Jan a marqué de son empreinte l’histoire du Haut Moyen Âge. Son oeuvre a accompagné l’évolution de la discipline historique depuis plus de quarante ans. Au gré de ses publications, de colloques, de programmes de recherche, de son enseignement, elle a donné à l’histoire du Haut Moyen Âge des orientations inédites. Pour lui rendre hommage, ses collègues, amis et élèves se sont inspirés de quelques-uns de ses thèmes de recherche privilégiés. Dans ce volume sont ainsi envisagés la place de l’aristocratie et des élites dans la société médiévale, l’analyse des réseaux qui structurent cette société ainsi que les enjeux que représentent les échanges compétitifs au haut Moyen Âge.Faire lien : c’est sous ce titre qu’ont été rassemblées les quarante-deux contributions organisées autour de ces sujets. Cet ouvrage est l’occasion de souligner une idée qui structure l’ensemble de l’oeuvre de Régine Le Jan : le rôle du lien social dans la société altimédiévale. Il rend également hommage à la place qu’a jouée Régine Le Jan dans la médiévistique occidentale, elle qui a su faire le lien entre l’histoire et les autres sciences sociales, entre la France et les autres pays européens, entre l’Europe et le continent américain, entre l’enseignement et la recherche

Splendor reginae. Passions, genre et famille: Mélanges en l'honneur de Régine Le Jan

International audienceRégine Le Jan a marqué de son empreinte l’histoire du Haut Moyen Âge. Son oeuvre a accompagné l’évolution de la discipline historique depuis plus de quarante ans. Au gré de ses publications, de colloques, de programmes de recherche, de son enseignement, elle a donné à l’histoire du Haut Moyen Âge des orientations inédites. Pour lui rendre hommage, ses collègues, amis et élèves se sont inspirés de quelques-uns de ses thèmes de recherche privilégiés au fil de trente articles rassemblés ici. Dans ce volume est d’abord envisagée l’importance de la famille et des liens de parenté dans les relations de pouvoir au Haut Moyen Âge, rappelant l’ouvrage fondateur que fut sa thèse "Famille et pouvoir dans le monde franc" (Publications de la Sorbonne, 1995). Sont ensuite évoquées celles dont elle a si bien montré le rôle essentiel par l’évocation de figures de femmes médiévales, tout en rappelant comment a continué à peser sur elles tout le poids d’une discrimination qui se poursuit endant toute la période. Enfin, les auteurs reviennent sur l’usage des émotions et du vocabulaire de la haine et de l’amitié, dont la place ne cesse de croître à la fois dans les domaines social et politique au fil du Haut Moyen Âge

A Cloned Frog Vasoactive Intestinal Polypeptide/ Pituitary Adenylate Cyclase-Activating Polypeptide Receptor Exhibits Pharmacological and Tissue Distribution Characteristics of Both VPAC1 and VPAC2 Receptors in Mammals*

International audienceThree receptor subtypes for the neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) have been identified in mammals: the PAC1 receptor (PAC1-R) which is selectively activated by PACAP, and two VPAC receptors (VPAC1-R and VPAC2-R), which are equally stimulated by PACAP and VIP. The structures of PACAP and VIP have been well conserved during evolution, but little is known about VIP/PACAP receptors in nonmammalian species. An amphibian VIP/PACAP receptor complementary DNA (cDNA) has been cloned and characterized from a frog (Rana ridibunda) pituitary cDNA library. The predicted protein contains seven putative transmembrane domains and exhibits the highest sequence identity (65%) with the human VPAC1-R. The cloned cDNA was transiently expressed in LLC-PK1 cells, and its pharmacological profile was determined in comparison with the human VPAC1-R. Both PACAP and VIP stimulated cAMP accumulation through the cloned receptor with an EC50 of about 30 nM. In contrast, secretin, at concentrations that stimulate the human VPAC1-R, had no effect on cAMP production. RT-PCR analysis revealed the widespread distribution of this frog VIP/PACAP receptor in peripheral tissues. In situ hybridization histochemistry using a complementary RNA probe showed that the receptor gene is highly expressed in several hypothalamic and thalamic nuclei and to a lesser extent in the pallium and striatum. In the pituitary, the highest messenger RNA levels were detected in the distal lobe. Taken together, these data show that the cloned frog receptor shares several common features with both the VPAC1-R and VPAC2-R of mammals; the frog receptor exhibits the highest sequence identity with mammalian VPAC1-R, but the lack of effect of secretin and the brain distribution of the receptor are reminiscent of the characteristics of the mammalian VPAC2-R. The sequence of the frog receptor should thus prove useful to decipher the structure-activity relationships of the VIP/PACAP receptor family

Cloning, sequence analysis and tissue distribution of the mouse and rat urotensin II precursors

International audienceUrotensin II (UII) is a cyclic neuropeptide initially isolated from the caudal neurosecretory system of teleost fish. The recent cloning of the UII precursor in frog and human has demonstrated that the peptide is not restricted to the fish urophysis but that it is also expressed in the central nervous system of tetrapods. Here, we describe the characterization of the cDNAs encoding prepro-UII in mouse and rat. A comparison of the primary structures of mouse and rat UII with those of other vertebrate UII reveals that the sequence of the cyclic region of the molecule (CFWKYC) has been fully conserved. In contrast, the N-terminal flanking domain of prepro-UII has markedly diverged with only 48% sequence identity between the mouse or rat and the human precursors. In situ hybridization histochemistry showed that the prepro-UII gene is predominantly expressed in motoneurons of the brainstem and spinal cord, suggesting that UII may play a role in the control of neuromuscular functions

Specific expression of the urotensin II gene in sacral motoneurons of developing rat spinal cord

International audienceThe neuropeptide urotensin II (UII) is expressed in motoneurons of the brainstem and spinal cord in adults. Here, the expression pattern of the UII gene was studied in the developing rat spinal cord. UII mRNA was detected by reverse-transcription-polymerase chain reaction (RT-PCR) as early as E10. From E14 to E21, in situ hybridization revealed intense expression of the UII gene specifically in sacral motoneurons, while only faint expression was detected at cervical and thoracic levels. After birth (P0, P4), the expression of UII mRNA increased in motoneurons at all rostrocaudal levels. Thus, UII is the first gene reported to show expression limited to the sacral pool of motoneurons, which are known to have particular properties in terms of targets and programmed cell death