Vincent Prevot

French Institute of Health and Medical Research | Inserm · Development and PLasticity of the Postnatal Brain

Background Polycystic ovary syndrome (PCOS) is the most common endocrine disorder leading to anovulatory infertility. Abnormalities in the central neuroendocrine system governed by gonadotropin-releasing hormone (GnRH) neurons might be related to ovarian dysfunction in PCOS, although the link in this disordered brain-to-ovary communication remains...

Disclosure: E.G. Mills: None. M. Swedrowska: None. V. Delli: None. K. Chachlaki: None. M. Silva: None. L. Decoster: None. G. Ternier: None. L. Thurston: None. M. Phylactou: None. B. Patel: None. L. Yang: None. S.A. Clarke: None. B. Muzi: None. E.C. Alexander: None. M. Choudhury: None. P. Bech: None. A. Abbara: None. B. Forbes: None. P. Giacobini: N...

Background We have recently demonstrated a causal link between loss of gonadotropin-releasing hormone (GnRH), the master molecule regulating reproduction, and cognitive deficits during pathological aging, including Down syndrome and Alzheimer's disease. Olfactory and cognitive alterations, which persist in some COVID-19 patients, and long-term hypo...

Here, we present a protocol for tanycyte-neuron paired whole-cell patch-clamp recording in living mouse brain slices. We describe steps for mice generation, solution preparation, and dissection. We then detail realization of slices and patch-clamp recordings. While we use, as an example, tanycytes of the arcuate nucleus of the hypothalamus and pro-...

Neddylation is a post-translational mechanism that adds a ubiquitin-like protein, namely neural precursor cell expressed developmentally downregulated protein 8 (NEDD8). Here, we show that neddylation in mouse liver is modulated by nutrient availability. Inhibition of neddylation in mouse liver reduces gluconeogenic capacity and the hyperglycemic a...

Older age is one of the strongest risk factors for severe COVID-19. In this study, we determined whether age-associated cellular senescence contributes to the severity of experimental COVID-19. Aged golden hamsters accumulate senescent cells in the lungs, and the senolytic drug ABT-263, a BCL-2 inhibitor, depletes these cells at baseline and during...

Adipocyte-derived leptin enters the brain to exert its anorexigenic action, yet its transport mechanism is poorly understood. Here we report that LRP1 (low density lipoprotein receptor-related protein-1) mediates the transport of leptin across the blood-CSF barrier in Foxj1 expressing cells highly enriched at the choroid plexus (ChP), coupled with...

Objective: O-GlcNAcylation is a post-translational modification that directly couples the processes of nutrient sensing, metabolism, and signal transduction, affecting protein function and localization, since the O-linked N-acetylglucosamine moiety comes directly from the metabolism of glucose, lipids, and amino acids. The addition and removal of...

Hypothalamic gonadotropin-releasing hormones (GnRH) neurons are central regulators of fertility and integrate endogenous hormonal status with environmental cues to ensure reproductive success. Here, we found that a novel population of extra-hypothalamic GnRH neurons in the olfactory bulb of adult mice and humans (GnRH OB ) can mediate social recogn...

Pulsatile secretion of gonadotropin-releasing hormone (GnRH) is essential for activating and maintaining the function of the hypothalamic-pituitary-gonadal (HPG) axis, which controls the onset of puberty and fertility. Two recent studies suggest that, in addition to controlling reproduction, the neurons in the brain that produce GnRH are also invol...

Background: Polycystic ovary syndrome (PCOS) is the most common reproductive-endocrine disorder affecting between 5 and 18% of women worldwide. An elevated frequency of pulsatile luteinizing hormone (LH) secretion and higher serum levels of anti-Müllerian hormone (AMH) are frequently observed in women with PCOS. The origin of these abnormalities i...

The median eminence (ME) is a circumventricular organ at the base of the brain that controls body homeostasis. Tanycytes are its specialized glial cells that constitute the ventricular walls and regulate different physiological states, however individual signaling pathways in these cells are incompletely understood. Here, we identify a functional t...

Objective: p63 is a transcription factor within the p53 protein family that has key roles in development, differentiation and prevention of senescence, but its metabolic actions remain largely unknown. Herein, we investigated the physiological role of p63 in glucose metabolism. Design: We used cell lines and mouse models to genetically manipulat...

The third ventricle (3V) wall of the tuberal hypothalamus is composed of two types of cells, specialized ependymoglial cells called tanycytes located ventrally and ependymocytes dorsally, which control the exchanges between the cerebrospinal fluid and the hypothalamic parenchyma. By regulating the dialogue between the brain and the periphery, tanyc...

The WATCH project: Tanycytes in health and disease In our aging societies, maintaining health and limiting age-related metabolic or cognitive disorders are of primordial importance not only for the well-being of the individual but also from the economic and societal points of view. The Synergy project Well-Aging and the Tanycytic Control of Health...

Food odour recognition is involved in the food anticipatory response. A study in Nature Metabolism describes how the olfactory system differentially regulates metabolic adaptations depending on energy availability. These effects are mediated by a brain circuit involving the melanocortin system that controls systemic lipid utilization via the sympat...

Mounting evidence suggests that the gut-to-lung axis is critical during respiratory viral infections. We herein hypothesized that disruption of gut homeostasis during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may associate with early disease outcomes. To address this question, we took advantage of the Syrian hamster mod...

Background The maturation of the hypothalamic-pituitary-gonadal (HPG) axis is crucial for the establishment of reproductive function. In female mice, neuronal nitric oxide synthase (nNOS) activity appears to be key for the first postnatal activation of the neural network promoting the release of gonadotropin-releasing hormone (GnRH), i.e. minipuber...

Therapies based on glucagon-like peptide-1 (GLP-1) long-acting analogs and insulin are often used in the treatment of metabolic diseases. Both insulin and GLP-1 receptors are expressed in metabolically relevant brain regions, suggesting a cooperative action. However, the mechanisms underlying the synergistic actions of insulin and GLP-1R agonists r...

The nitric oxide (NO) signaling pathway in hypothalamic neurons plays a key role in the regulation of the secretion of gonadotropin-releasing hormone (GnRH), which is crucial for reproduction. We hypothesized that a disruption of neuronal NO synthase (NOS1) activity underlies some forms of hypogonadotropic hypogonadism. Whole-exome sequencing was p...

Objectif Étudier l’efficacité à un et trois mois d’un traitement en première intention par lanréotide 120 mg sur la réduction du volume tumoral (VT) et l’amélioration des atteintes ophtalmologiques chez des patients nouvellement diagnostiqués d’acromégalie. Patients et méthodes Dans cette étude monocentrique, 21 patients atteints d’acromégalie de...

Objectif Nous avons d’abord cherché à établir l’intervalle de référence pour les concentrations sériques d’AMH chez des hommes adultes. Deuxièmement, nous avons étudié la relation entre les concentrations sériques d’AMH et les gonadotrophines, la testostérone totale ainsi que les paramètres spermatiques. Patients et méthodes Au total, 578 hommes a...

At the present time, no viable treatment exists for cognitive and olfactory deficits in Down syndrome (DS). We show in a DS model (Ts65Dn mice) that these progressive nonreproductive neurological symptoms closely parallel a postpubertal decrease in hypothalamic as well as extrahypothalamic expression of a master molecule that controls reproduction-...

Narcolepsy type 1 (NT1) is a rare neurological sleep disorder triggered by postnatal loss of the orexin/hypocretin neuropeptides. Overweight/obesity and precocious puberty are highly prevalent comorbidities of NT1, with a close temporal correlation with disease onset, suggesting a common origin. However, the underlying mechanisms remain unknown and...

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a multi-organ damage that includes hepatic dysfunction, which has been observed in over 50% of COVID-19 patients. Liver injury in COVID-19 could be attributed to the cytopathic effects, exacerbated immune responses or treatment-associated drug toxicity. Herein we demonstrate that h...

Kiss1 neurons, producing kisspeptins, are essential for puberty and fertility, but their molecular regulatory mechanisms remain unfolded. Here, we report that congenital ablation of the microRNA-synthesizing enzyme, Dicer, in Kiss1 cells, causes late-onset hypogonadotropic hypogonadism in both sexes, but is compatible with pubertal initiation and p...

Women with polycystic ovary syndrome (PCOS) frequently experience decreased sexual arousal, desire, and sexual satisfaction. While the hypothalamus is known to regulate sexual behavior, the specific neuronal pathways affected in patients with PCOS are not known. To dissect the underlying neural circuitry, we capitalized on a robust preclinical anim...

COVID-19 is a complex disease with short- and long-term respiratory, inflammatory and neurological symptoms that are triggered by the infection with SARS-CoV-2. Invasion of the brain by SARS-CoV-2 has been observed in humans and is postulated to be involved in post-COVID state. Brain infection is particularly pronounced in the K18-hACE2 mouse model...

Early-life determinants are thought to be a major factor in the rapid increase of obesity. However, while maternal nutrition has been extensively studied, the effects of breastfeeding by the infant on the reprogramming of energy balance in childhood and throughout adulthood remain largely unknown. Here we show that delayed weaning in rat pups prote...

Communication between the periphery and the brain is key for maintaining energy homeostasis. To do so, peripheral signals from the circulation reach the brain via the circumventricular organs (CVOs), which are characterized by fenestrated vessels lacking the protective blood–brain barrier (BBB). Glial cells, by virtue of their plasticity and their...

Liraglutide, an anti-diabetic drug and agonist of the glucagon-like peptide one receptor (GLP1R), has recently been approved to treat obesity in individuals with or without type 2 diabetes. Despite its extensive metabolic benefits, the mechanism and site of action of liraglutide remain unclear. Here, we demonstrate that liraglutide is shuttled to t...

Introduction: Few studies have attempted to evaluate the early efficacy of first-generation somatostatin analogs in somatotroph macroadenomas. Objective: To investigate the short-term efficacy of primary therapy with lanreotide 120 mg at one and three months on tumor shrinkage and ophthalmologic symptoms in newly diagnosed patients with acromegaly....

The accumulation of pathological Tau in the brain and cerebrospinal fluid (CSF) and its eventual increase in the blood are hallmarks of Alzheimer’s disease (AD). However, the mechanisms of Tau clearance from the brain to the periphery are not clear. We show here, using animal and cellular models as well as patient blood samples and post mortem brai...

Abstract Background: Few studies to date have attempted to measure serum anti-Müllerian hormone (AMH) levels in adult men, and solid references ranges have not yet been defined on a large cohort. Objective: In this study, we aimed to first establish the reference ranges for serum AMH and AMH-to-total testosterone ratio (AMH/tT) in adult males. Sec...

Background Few studies to date have attempted to measure serum anti-Müllerian hormone (AMH) levels in adult men, and solid references ranges have not yet been defined on a large cohort. Objective In this study, we aimed to first establish the reference ranges for serum AMH and AMH-to-total testosterone ratio (AMH/tT) in adult males. Secondly, we i...

Introduction: Few studies have attempted to evaluate the early efficacy of first-generation somatostatin analogs in somatotroph macroadenomas. Objective: To investigate the short-term efficacy of primary therapy with lanreotide 120 mg at one and three months on tumor shrinkage and ophthalmologic symptoms in newly diagnosed patients with acromega...

In adult mammals, neural stem cells are localized in three neurogenic regions, the subventricular zone of the lateral ventricle (SVZ), the subgranular zone of the dentate gyrus of the hippocampus (SGZ) and the hypothalamus. In the SVZ and the SGZ, neural stem/progenitor cells (NSPCs) express the glial fibrillary acidic protein (GFAP) and selective...

To ensure the survival of the species, hypothalamic neuroendocrine circuits controlling fertility, which converge onto neurons producing gonadotropin‐releasing hormone (GnRH), must respond to fluctuating physiological conditions by undergoing rapid and reversible structural and functional changes. However, GnRH neurons do not act alone, but through...

Background & Aims The pathogenesis of liver fibrosis requires activation of hepatic stellate cells (HSCs); once activated, HSCs lose intracellular fatty acids but the role of fatty acid oxidation and carnitine palmitoyltransferase 1A (CPT1A) in this process remains largely unexplored. Methods CPT1A was found in HSCs of patients with fibrosis. Phar...

The suprachiasmatic nucleus (SCN) synchronizes physiology with the individual’s environment to optimize bodily functions. A new study reveals that tanycytes follow the tempo set by the SCN to effect circadian changes in both brain entry of blood glucose and glycemia.

COVID-19 is a complex disease with short- and long-term respiratory, inflammatory and neurological symptoms that are triggered by the infection with SARS-CoV-2. Invasion of the brain by SARS-CoV-2 has been observed in humans and is postulated to be involved in post COVID condition. Brain infection is particularly pronounced in the K18-hACE2 mouse m...

The solute carrier monocarboxylate transporter 8 (MCT8) transports the thyroid hormones thyroxine and tri-iodothyronine (T3) across cell membranes. MCT8 gene deficiency, termed Allan-Herndon-Dudley syndrome, is an important cause of X-linked intellectual and motor disability. As no treatment of the neurological symptoms is available yet, we tested...

Neurons that produce gonadotropin-releasing hormone (GnRH), which control fertility, complete their nose-to-brain migration by birth. However, their function depends on integration within a complex neuroglial network during postnatal development. Here, we show that rodent GnRH neurons use a prostaglandin D2 receptor DP1 signaling mechanism during i...

Neuroinvasion by SARS-CoV-2 is now accepted. To investigate whether low testosterone levels observed in men with severe COVID-19 could be of central origin, we retrospectively analyzed blood samples from 60 male intensive-care patients and explored SARS-CoV-2 brain entry using animal and cellular models as well as adult COVID-19 patient and fetal h...

Coronavirus disease 2019 (COVID-19) can damage cerebral small vessels and cause neurological symptoms. Here we describe structural changes in cerebral small vessels of patients with COVID-19 and elucidate potential mechanisms underlying the vascular pathology. In brains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected indivi...

Melanin-concentrating hormone (MCH) is a small cyclic peptide expressed in all mammals, mainly in the hypothalamus. MCH acts as a robust integrator of several physiological functions and has crucial roles in the regulation of sleep–wake rhythms, feeding behaviour and metabolism. MCH signalling has a very broad endocrine context and is involved in p...

Introduction et objectifs La réussite d’une gestation nécessite une grande plasticité structurale et fonctionnelle dans le système nerveux central, comme par exemple une neurogenèse dans la zone sous-ventriculaire et les bulbes olfactifs chez le rongeur. En raison du rôle crucial de l’hypothalamus dans le contrôle central de la reproduction et du c...

Introduction et objectifs Les subépendymomes sont des tumeurs du système nerveux central bégnines (OMS grade I), rares, se développant en bordure des cavités ventriculaires mais dont l’origine cellulaire demeure incertaine [1]. Dans une étude précédente, nous avons mis en évidence une population de cellules présentant un profil antigénique de cellu...

Background & aims: Autophagy-related gene 3 (ATG3) is an enzyme mainly known for its actions in the LC3 lipidation process, which is essential for autophagy. Whether ATG3 plays a role in lipid metabolism or contributes to nonalcoholic fatty liver disease (NAFLD) remains unknown. Methods: By performing a liver proteomic analysis from mice with ge...

Gene vectors targeting CNS endothelial cells allow to manipulate the blood-brain barrier and to correct genetic defects in the CNS. Because vectors based on the adeno-associated virus (AAV) have a limited capacity, it is essential that the DNA sequence controlling gene expression is short. In addition, it must be specific for endothelial cells to a...

In adult mammals, neural stem cells emerge in three neurogenic regions, the subventricular zone of the lateral ventricle (SVZ), the subgranular zone of the dentate gyrus of the hippocampus (SGZ) and the hypothalamus. In the SVZ and the SGZ, neural stem/progenitor cells (NSPCs) express the glial fibrillary acidic protein (GFAP) and selective ablatio...

Metabolic health depends on the brain’s ability to control food intake and nutrient use versus storage, processes that require peripheral signals such as the adipocyte-derived hormone, leptin, to cross brain barriers and mobilize regulatory circuits. We have previously shown that hypothalamic tanycytes shuttle leptin into the brain to reach target...