Prenatal Androgen Exposure Induces Anxiety-Like Behavior in Ewes.

Introduction: In humans, prenatal androgen excess can lead to a broad spectrum of pathologies in adulthood, including polycystic ovary syndrome (PCOS). Women with PCOS present a variety of reproductive and metabolic disturbances and they also face increased risk to develop neuropsychiatric disorders such as depression and anxiety. Despite the high prevalence, the cause of depressive and anxiety symptoms is not fully elucidated.

Quantitation of endogenous GnRH by validated nano-HPLC-HRMS method: a pilot study on ewe plasma.

Gonadotropin-releasing hormone isoform I (GnRH), a neuro-deca-peptide, plays a fundamental role in development and maintenance of the reproductive system in vertebrates. The anomalous release of GnRH is observed in reproductive disorder such as hypogonadotropic hypogonadism, polycystic ovary syndrome (PCOS), or following prenatal exposure to elevated androgen levels. Quantitation of GnRH plasma levels could help to diagnose and better understand these pathologies.

The great migration: How glial cells could regulate GnRH neuron development and shape adult reproductive life.

In mammals, reproductive function is under the control of hypothalamic neurons named Gonadotropin-Releasing Hormone (GnRH) neurons. These neurons migrate from the olfactory placode to the brain, during embryonic development. For the past 40 years, these neurons have been considered an example of tangential migration, i.

SELENOT Deficiency in the Mouse Brain Impacts Catecholaminergic Neuron Density: An Immunohistochemical, in situ Hybridization and 3D Light-Sheet Imaging Study.

Background: Selenoprotein T (SELENOT), a PACAP-regulated thioredoxin-like protein, plays a role in catecholamine secretion and protects dopaminergic neurons. However, the role of SELENOT in the establishment of the catecholaminergic (CA) neuronal system is not known yet.

Methods: We analyzed by immunohistochemistry and RNAscope in situ hybridization the distribution of SELENOT and the expression of its mRNA, respectively.

Magnetic Resonance Imaging, a New Tool for Neuroendocrine Research in Sheep.

Magnetic resonance imaging (MRI) brain analysis is used in rodents and for clinical investigation in humans, and it becomes also possible now for large animal models studies. Specific facilities are available with clinical scanners and benefit to neuroendocrine investigations in sheep. Sheep has a large gyrencephalic brain and its organization is very similar to primates and human, and among physiological regulations, oestrous cycle of the ewes is similar to women.

Application of Chemical Exchange Saturation Transfer (CEST) in neuroimaging.

Since the early eighties MRI has become the most powerful technic for in-vivo imaging particularly in the field of brain research. This non-invasive method allows acute anatomical observations of the living brain similar to post-mortem dissected tissues. However, one of the main limitation of MRI is that it does not make possible the neurochemical identification of the tissues conversely to positron emission tomography scanner which can provide a specific molecular characterization of tissue, in spite of poor anatomical definition.

Rostro-caudal maturation of glial cells in the accessory olfactory system during development: involvement in outgrowth of GnRH neurites.

During mammalian embryonic development, GnRH neurones differentiate from the nasal placode and migrate through the nasal septum towards the forebrain. We previously showed that a category of glial cells, the olfactory ensheathing cells (OEC), forms the microenvironment of migrating GnRH neurones. Here, to characterize the quantitative and qualitative importance of this glial, we investigated the spatiotemporal maturation of glial cells in situ and the role of maturing glia in GnRH neurones development ex vivo.

[Orphan Drugs: Underrated Opportunities for The Developers in Europe].

In Europe, rules relating to the designation and the protection of orphan drug are derived from regulation (EC) 141/2000 of the European Parliament and Council of 16 December 1999, specified by the implementing Regulation (EC) 847/2000. According to these regulations, obtaining the status of orphan drugs implies, in particular, to demonstrate the absence of any satisfying alternative treatment, or, by default, the significant benefit offered by the concerned drug. In the same sense, medicinal product similar to an original orphan medicinal product but safer, more effective or otherwise clinically superior, will benefit from a derogation to the rules on the 10 years market exclusivity usually provided for these products.

Different distributions of preproMCH and hypocretin/orexin in the forebrain of the pig (Sus scrofa domesticus).

Neurons producing melanin-concentrating hormone (MCH) or hypocretin/orexin (Hcrt) have been implicated in the sleep/wake cycle and feeding behavior. Sleep and feeding habits vary greatly among mammalian species, depending in part of the prey/predatory status of animals. However, the distribution of both peptides has been described in only a limited number of species.

Evidence that histaminergic neurons are devoid of estrogen receptor alpha in the ewe diencephalon during the breeding season.

In sheep as in rat, it has been highly suggested that neuronal histamine (HA) participates to the estradiol (E2)-induced GnRH and LH surges, through H1 receptor. With the aim of determining if E2 could act directly on HA neurons, we examined here whether HA neurons express estrogen receptor alpha (ERα) in the ewe diencephalon during the breeding season. We first produced a specific polyclonal antibody directed against recombinant ovine histidine decarboxylase (oHDC), the HA synthesizing enzyme.

Evaluation of the activity and safety of CS21 barrier genital gel® compared to topical aciclovir and placebo in symptoms of genital herpes recurrences: a randomized clinical trial.

Background: Topical or systemic antiviral drugs reduce the duration of genital herpes recurrences but may not always alleviate functional symptoms.

Objectives: To assess the efficacy and safety of oxygenated glycerol triesters-based CS21 barrier genital gel(®) vs. topical aciclovir and placebo (vehicle) in resolving functional symptoms and in healing of genital herpes recurrences.

Olfactory ensheathing cells form the microenvironment of migrating GnRH-1 neurons during mouse development.

During development, GnRH-1 neurons differentiate extracerebraly from the nasal placode and migrate from the vomeronasal organ to the forebrain along vomeronasal and terminal nerves. Numerous studies have described the influence of different molecules on the migration of GnRH-1 neurons, however, the role of microenvironment cells remains poorly understood. This study used GFAP-GFP transgenic mice to detect glial cells at early developmental stages.

[The adoption of Jardé law modifies the legal framework of clinical research in France].

The Jardé law is adopted further to the Public Health Act No. 2004-806 which transposed into French law the Directive 2001/20/EC on clinical trials of medicinal products, made effective by the implementing Decree 2006-477 of April 26, 2006. The main novelty introduced by the Jardé law is to unify all "research organized and practiced on human beings for the development of biological or medical knowledge" and to facilitate its effective conduct, without however excluding from the scope of the law routine care and non-interventional research.

Embryonic development of kisspeptin neurones in rat.

Kisspeptins, encoded by the Kiss1 gene, play a key role in the regulation of reproductive function, although very little is known about the ontogenesis of this system. The present study aimed to determine the period of arcuate nucleus (ARC) kisspeptin cell birth and the embryonic stage and neuroanatomical sites of onset of kisspeptin immunoreactivity. Bromodeoxyuridine (BrdU) was administered to female rats at various gestational stages and double immunohistochemistry against kisspeptin and BrdU was performed on brain sections from their offspring.

[Reform Act on safety of drug and health products in France: announcement effect, strengthening or upheaval?].

In France, the Médiator(®) scandal and the trauma it has created, are the source of Law n° 2011-2012 of 29 December 2011 on strengthening safety of drug and health products, intended by the Ministry of Labour, Employment and Health, adopted by the National Assembly and promulgated in order to restore confidence and enhance safety of drug and health products. This new law affects all stakeholders and health professionals impacts key points in the life cycle of the drug: MA, reimbursement, advertising, promotion, distribution, prescription, dispensing, and pharmacovigilance. It also provides for financial, administrative or criminal penalties, which are intended deterrent.

Morphofunctional interactions between galanin and GnRH-containing neurones in the diencephalon of the ewe. The effect of oestradiol.

In rodents, the neuropeptide galanin (Gal) is involved in controlling the release of gonadotrophin-releasing hormone (GnRH). In the female, this peptide is colocalized in a subpopulation of GnRH neurones and its expression is stimulated by oestradiol. In the ewe, the morphofunctional relationship between these two neuronal peptides is poorly understood.

Evaluation of the efficacy and safety of a CS20® protective barrier gel containing OGT compared with topical aciclovir and placebo on functional and objective symptoms of labial herpes recurrences: a randomized clinical trial.

Background: Topical or systemic antiviral drugs reduce the duration of herpes simplex virus 1 (HSV-1) recurrences but may not alleviate functional symptoms.

Objectives: To assess the efficacy and safety of CS20 (Acura 24(®) ) protective barrier gel versus topical aciclovir and placebo in resolving functional symptoms in HSV-1 labial recurrences.

Methods: A prospective, randomized, single-centre, assessor-blinded study of CS20 versus topical aciclovir or placebo.

Mapping of kisspeptin fibres in the brain of the pro-oestrous rat.

Kisspeptins are a family of small peptides that play a key role in the neuroendocrine regulation of the reproductive function through neural pathways that have not yet been completely identified. The present study aimed to investigate the distribution of kisspeptin neurone fibres in the female rat brain by comparing precisely the immunoreactive pattern obtained with two antibodies: one specifically directed against kisspeptin-52 (Kp-52), the longest isoform, and the other directed against kisspeptin-10 (Kp-10), whose sequence is common to all putative mature isoforms. With both antibodies, immunoreactive cell bodies were exclusively observed in the arcuate nucleus, and immunoreactive fibres were confined to the septo-preoptico-hypothalamic continuum of the brain.