Didier Vieau

University of Lille · Department of Biology

Adenosine is an ubiquitous neuromodulator that ensures cerebral homeostasis. It exerts numerous functions through the activation of G-protein-coupled adenosine receptors (ARs), in particular A 1 (A 1 R) and A 2A (A 2A R) receptors. Interestingly, A 2A R levels are upregulated in cortical and hippocampal regions in several pathological conditions su...

Early pathological upregulation of adenosine A2A receptors (A2ARs), one of the caffeine targets, by neurons is thought to be involved in the development of synaptic and memory deficits in Alzheimer’s disease (AD) but mechanisms remain ill-defined. To tackle this question, we promoted a neuronal upregulation of A2AR in the hippocampus of APP/PS1 mic...

Early-life exposure to high-fat diets (HF) can program metabolic and cognitive alterations in adult offspring. Although the hippocampus plays a crucial role in memory and metabolic homeostasis, few studies have reported the impact of maternal HF on this structure. We assessed the effects of maternal HF during lactation on physiological, metabolic,...

Early-life exposure to high-fat diet (HF) can program metabolic and cognitive alterations in adult offspring. Although the hippocampus plays a crucial role in memory and metabolic homeostasis, few studies reported the impact of maternal HF on this structure. We assessed the effects of maternal HF during lactation on physiological, metabolic and cog...

Caffeine is the most consumed psychoactive substance worldwide. Strikingly, molecular pathways engaged by its regular consumption remain unclear. We herein addressed the mechanisms associated with habitual (chronic) caffeine consumption in the mouse hippocampus using untargeted orthogonal-omics techniques. Our results revealed that chronic caffeine...

With the expand of the population’s average age, the incidence of neurodegenerative disorders has dramatically increased over the last decades. Alzheimer disease (AD) which is the most prevalent neurodegenerative disease is mostly sporadic and primarily characterized by cognitive deficits and neuropathological lesions such as amyloid -β (Aβ) plaque...

Alzheimer’s disease (AD) is the leading cause of dementia. While impaired glucose homeostasis has been shown to increase AD risk and pathological loss of tau function, the latter has been suggested to contribute to the emergence of the glucose homeostasis alterations observed in AD patients. However, the links between tau impairments and glucose ho...

Alzheimer's disease is the most common form of dementia characterized by intracellular aggregates of hyperphosphorylated Tau protein and extracellular accumulation of amyloid β (Aβ) peptides. We previously demonstrated that the purinergic receptor P2X7 (P2X7) plays a major role in Aβ-mediated neurodegeneration but the relationship between P2X7 and...

Les patients atteints d’une maladie d’Alzheimer (MA), dont une des lésions caractéristiques est la présence d’agrégats cérébraux de protéines Tau, présentent fréquemment des troubles de l’homéostasie glucidique. De manière intéressante, chez les patients atteints de MA, les agrégats de protéines Tau, conduisant à une perte de la fonction physiologi...

Worldwide, the number of people with diabetes has quadrupled since 1980 reaching 422 million in 2014 (World Health Organization). This distressing rise in diabetes also affects pregnant women and thus, in regard to early programming of adult diseases, creates a vicious cycle of metabolic dysfunction passed from one generation to another. Metabolic...

Clinical and animal studies have reported an association between low birth weight and the development of non-alcoholic fatty liver disease (NAFLD) in offspring. Using a model of prenatal maternal 70% food restriction diet (FR30) in rat, we previously showed that maternal undernutrition predisposes offspring to altered lipid metabolism in adipose ti...

Purpose Poor maternal nutrition sensitises to the development of metabolic diseases and obesity in adulthood over several generations. The prevalence increases when offspring is fed with a high-fat (HF) diet after weaning. This study aims to determine whether such metabolic profiles can be transmitted to the second generation and even aggravated wh...

Adenosine A2A receptors (A2AR) are modulators of various physiological processes essential for brain homeostasis and fine synaptic tuning. In certain neurodegenerative conditions, notably Alzheimer's disease (AD), A2ARs are pathologically upregulated in neurons but also in astrocytes. In that context, the use of A2ARs inhibitors, normalizing impair...

Tau protein which was discovered in 1975 [310] became of great interest when it was identified as the main component of neurofibrillary tangles (NFT), a pathological feature in the brain of patients with Alzheimer’s disease (AD) [39, 110, 232]. Tau protein is expressed mainly in the brain as six isoforms generated by alternative splicing [46, 97]....

Résumé La maladie d’Alzheimer (MA) est une maladie neurodégénérative caractérisée par des déficits cognitifs et des lésions neuropathologiques (agrégats de Tau et plaques amyloïdes), mais également par des troubles métaboliques et neuroendocriniens. Les mécanismes à l’origine de ces processus physiopathologiques demeurent mal compris mais pourraien...

Alzheimer's disease (AD) is a neurodegenerative disease primarily characterized by cognitive deficits and neuropathological lesions such as Tau aggregates and amyloid plaques, but also associated with metabolic and neuroendocrine abnormalities, such as impairment of cerebral insulin. However, the origin of these symptoms and their relationship to p...

Alzheimer’s disease (AD) is the most common neurodegenerative disorder in elderly people. AD is characterized by a progressive cognitive decline and it is neuropathologically defined by two hallmarks: extracellular deposits of aggregated β-amyloid (Aβ) peptides and intraneuronal fibrillar aggregates of hyper- and abnormally phosphorylated Tau prote...

br>Alzheimer's disease (AD) is a progressive neurodegenerative disorder mainly characterized by cognitive deficits and neuropathological changes such as Tau lesions and amyloid plaques, but also associated with non-cognitive symptomatology. Metabolic and neuroendocrine abnormalities, such as alterations in body weight, brain insulin impairments and...

Neurodegenerative diseases (NDDs) are disorders characterized by progressive deterioration of brain structure and function. Selective neuronal populations are affected leading to symptoms which are prominently motor in amyotrophic lateral sclerosis (ALS) or Huntington’s disease (HD), or cognitive in Alzheimer’s disease (AD) and fronto-temporal deme...

According to the Developmental Origin of Health and Disease (DOHaD) concept, maternal obesity and accelerated growth in neonates program obesity later in life. White adipose tissue (WAT) has been the focus of developmental programming events, although underlying mechanisms remain elusive. In rodents, WAT development primarily occurs during lactatio...

The molecular pathways underlying tau pathology–induced synaptic/cognitive deficits and neurodegeneration are poorly understood. One prevalent hypothesis is that hyperphosphorylation, misfolding, and fibrillization of tau impair synaptic plasticity and cause degeneration. However, tau pathology may also result in the loss of specific physiological...

Objective According to the Developmental Origin of Health and Disease (DOHaD) concept, maternal obesity and accelerated growth in neonates predispose offspring to white adipose tissue (WAT) accumulation. In rodents, adipogenesis mainly develops during lactation. The mechanisms underlying the phenomenon known as developmental programming remain elus...

Based on the Developmental Origin of Health and Disease concept, maternal undernutrition has been shown to sensitize adult offspring to metabolic pathologies such as obesity. Using a model of maternal 70% food restriction in pregnant female rats throughout gestation (called FR30), we previously reported that obesity-prone adult male rat offspring d...

Introduction et but de l’étude Le concept de l’origine développementale de la santé et des maladies (DOHaD) stipule qu’un environnement périnatal délétère prédispose la descendance à l’apparition de troubles métaboliques. En particulier, l’obésité maternelle, la surnutrition des nouveau-nés et la croissance postnatale accélérée sensibilisent la des...

According to the Developmental Origin of Health and Disease (DOHaD) concept, alterations of nutrient supply in the fetus or neonate result in long-term programming of individual body weight set-point. In particular, maternal obesity, excessive nutrition and accelerated growth in neonates have been shown to sensitize offspring to obesity. The white...

The nutritional imprinting, whose mechanisms remain still dark and which seem to continue through the following generations, highlight the key-role of the inadequacy between the pre-and postnatal nutritional environment and the programming of the obesity. © 2016 médecine/sciences – Inserm.

The adequate control of glucose homeostasis during both gestation and early postnatal life is crucial for the development of the fetoplacental unit and adaptive physiological responses at birth. Growing evidences indicate that apelin and its receptor APJ, which are expressed across a wide range of tissues, exert important roles in glucose homeostas...

The long-term effects of the development of chronic metabolic diseases such as type 2 diabetes and obesity have been associated with nutritional insults in critical life stages. In this study, we evaluated the effect of a low-protein diet on metabolism in mid-adulthood male rats. At 90 days of age, Wistar male rats were fed a low-protein diet (4.0...

A close link between intrauterine growth restriction (IUGR) and development of chronic adult diseases such as obesity, diabetes and hypertension has been established both in humans and animals. Modification of growth velocity during early postnatal period (i.e. lactation) may also sensitize to the development of metabolic syndrome in adulthood. Thi...

Aim. Chronic diseases are the leading cause of death worldwide. Advanced glycation end products, known as AGEs, are a major risk factor for diabetes onset and maintenance. Methylglyoxal (MG), a highly reactive metabolite of glucose, is a precursor for the generation of endogenous AGEs. Methods. In this current study we incubated in vitro pancreatic...

Undernutrition exposure during the perinatal period reduces the growth kinetic of the offspring and sensitizes it to the development of chronic adult metabolic diseases both in animals and in humans. Previous studies have demonstrated that a 50% maternal food restriction performed during the last week of gestation and during lactation has both shor...

Aims: We have previously demonstrated that central apelin is implicated in the control of peripheral glycemia, and its action depends on nutritional (fast versus fed) and physiological (normal versus diabetic) states. Intracerebroventricular (icv) injection of a high-dose of apelin, similar to that observed in obese/diabetic mice, increase fasted g...

Epidemiological studies initially suggested that maternal undernutrition leading to low birth weight may predispose for long-lasting energy balance disorders. High birth weight due to maternal obesity or diabetes, inappropriate early postnatal nutrition, and rapid catch-up growth, may also sensitize to increased risk of obesity. As stated by the De...

Epidemiological studies initially demonstrated that maternal undernutrition results in low birth weight with increased risk for long-lasting energy balance disorders. Maternal obesity and diabetes associated with high birth weight, excessive nutrition in neonates and rapid catch-up growth also increase the risk of adult-onset obesity. As stated by...

Aims: We have previously demonstrated that central apelin is implicated in the control of peripheral glycemia, and its action depends on nutritional (fast versus fed) and physiological (normal versus diabetic) states. An intracerebroventricular (icv) injection of a high dose of apelin, similar to that observed in obese/diabetic mice, increase fast...

Mild gestational hyperglycemia is often associated with fetal overgrowth that can predispose the offspring to metabolic diseases later in life. We hypothesized that unfavorable intrauterine environment may compromise the development of placenta and contribute to fetal overgrowth. Therefore, we developed a rat model and investigated the effects of m...

Macrosomia is defined as mean ± 1.7 SD of control body weight and expressed as percentage for male (A) and female (B). (TIF)

Blood glucose concentrations following an oral ingestion of glucose in pregnant controls and N-STZ females (n = 4–6) at GD19 and AUC of blood glucose concentrations. The effect of treatment was analyzed by one-way ANOVA followed by the Bonferroni posthoc test. Values represent mean ± SD. * p<0.05. **p<0.01 show the significant differences between c...

Epidemiological studies demonstrated that adverse environmental factors leading to intrauterine growth retardation (IUGR) and low birth weight may predispose individuals to increased risk of metabolic syndrome. In rats, we previously demonstrated that adult male IUGR offspring from prenatal 70% food-restricted dams throughout gestation (FR30) were...

Previous data reported that a noxious neonatal environment alters brain development and is responsible for diseases in adulthood (metabolic syndrome, obesity). With advances in medical care over the last two decades, the number of newborn infants exposed to chronic pain has considerably increased, and this has led to the augmentation of the use of...

Genetic variants in the FTO (fat mass- and obesity-associated) gene have the highest association of all obesity-associated genes. Its placental expression was shown to relate to birth weight, suggesting that it may participate in the control of fetal weight gain. To gain more insight into the implication of FTO in fetal growth, we measured its plac...

Males and females responses to gestational overnutrition set the stage for subsequent sex-specific differences in adult onset non communicable diseases. Placenta, as a widely recognized programming agent, contibutes to the underlying processes. According to our previous findings, a high-fat diet during gestation triggers sex-specific epigenetic alt...

Histograms of epigenetic machinery expression levels in microarrays and RT-qPCR. Line indicates statistical significance and the number refers to log2 fold change. (PDF)

Analysis of E15.5 placental structure. on HE-stained paraffin sections, of the placental layers in female and males (F or M) from mother fed a control (CD) or high-fat (HFD) diet. (A) Details of the labyrinth layer. (B) Details of the junctional zone. Scale bars indicate 200 µm. (C) Measurement of the area and shape of the labyrinth and total place...

Limma tables for the 4 comparisons (F HFD vs CD, M HFD vs CD, CD F vs M, HFD F vs M). Excel file. (XLS)

Low birth weight is associated with an increased risk to develop type 2 diabetes and metabolic diseases. The placental capacity to supply nutrients and oxygen to the fetus represents the main determiner of fetal growth. However, few studies have investigated the effects of maternal diet on the placenta. We explored placental adaptive proteomic proc...

Le dimorphisme sexuel s'établit dès la conception, avant même l'intervention des hormones. Il dé­pend des chromosomes sexuels et de l'expression des gènes soumis à l'influence de l'environnement. Influence elle-même transmissible au fil des géné­rations.L'AMP prédispose à un faible«sur» risque de cer­taines pathologies très rares. Ces anomalies son...

Epidemiological studies have shown that maternal undernutrition during pregnancy (MU) leads to intrauterine growth retardation and low birth weight, and may predispose individuals to the development of metabolic syndrome symptoms later in life such as overweight. Some clues from a model of prenatal maternal 70% food-restricted diet throughout gesta...

Data indicate that perinatal nutritional insults not onlyhave short-term consequences on the growth velocity of the fetus/neonate but also sensitize to the development of metabolic adult diseases. The pathophysiological mechanisms involved in the so-called "Developmental Origin of Health and Adult Diseases" are still largely unknown and depend on t...

Selenoproteins contain the essential trace element selenium whose deficiency leads to major disorders including cancer, male reproductive system failure, or autoimmune thyroid disease. Up to now, 25 selenoprotein-encoding genes were identified in mammals, but the spatiotemporal distribution, regulation, and function of some of these selenium-contai...

Several studies have shown that maternal undernutrition leading to low birth weight predisposes offspring to the development of metabolic pathologies such as obesity. Using a model of prenatal maternal 70% food restriction diet (FR30) in rat, we evaluated whether postweaning high-fat (HF) diet would amplify the phenotype observed under standard die...

An association is established between schizophrenia and the development of metabolic alterations including cardiovascular diseases, type 2 diabetes and obesity. Perinatal insults, such as undernutrition, have been shown to increase the propensity to develop these pathologies, reinforcing the idea that schizophrenia may have a neurodevelopmental ori...

Epidemiological studies suggest that maternal undernutrition sensitises to the development of chronic adult diseases, such as type 2 diabetes, hypertension and obesity. Although the physiological mechanisms involved in this 'perinatal programming' remain largely unknown, alterations of stress neuroendocrine systems such as the hypothalamic-pituitar...

Epidemiological and experimental data indicate that maternal undernutrition may sensitize the offspring to the apparition of chronic diseases such as metabolic syndrome and schizophrenia, suggesting that these pathologies may have a developmental origin. To test this hypothesis, we have compared the effects of a 4 weeks treatment of clozapine (30 m...