Sara Morley-Fletcher

Université de Lille · Unité de Glycobiologie Structurale et Fonctionnelle (UGSF)

The rat model of perinatal stress (PRS), in which exposure of pregnant dams to restraint stress reduces maternal behavior, is characterized by a metabolic profile that is reminiscent of the “metabolic syndrome”. We aimed to identify plasma metabolomic signatures linked to long-term programming induced by PRS in aged male rats. This study was conduc...

Early-life stressful situations and binge drinking have been thus far acknowledged as two burdensome conditions that potentially give rise to negative outcomes and then synergistically affect brain development. In this context, the hippocampus, with the greatest number of glucocorticoid receptors (GCRs) in the brain, is responsible for regulating n...

Both prenatal ethanol and early-life stress have been shown to induce reduced risk-taking and explorative behavior as well as cognitive dysfunction in the offspring. In this study, we examined the effect of combined exposure to ethanol and early stress on maternal care, exploratory behavior, memory performances, and oxidative stress in male offspri...

Objectif Le sommeil et le stress s’influencent réciproquement. En particulier, les stress qui surviennent pendant la période périnatale ont des effets de programmation à vie sur les troubles du SNC à l’âge adulte. Nous avons mis en place un modèle animal de stress périnatal (PRS) chez le rat qui présente des troubles du sommeil à l’âge adulte chez...

Brain aging may be programmed by early-life stress. Aging affects males and females differently, but how perinatal stress (PRS) affects brain aging between sexes is unknown. We showed behavioral and neurobiological sex differences in non-stressed control rats that were strongly reduced or inverted in PRS rats. In particular, PRS decreased risk-taki...

Antibodies recognizing the amino-terminal domain of receptor subunit proteins modify the receptor efficiency to controlling transmitter release in isolated nerve endings (e.g., synaptosomes) indirectly confirming their presence in these particles but also allowing to speculate on their subunit composition. Western blot analysis and confocal microsc...

Early-life stress involved in the programming of stress-related illnesses can have a toxic influence on the functioning of the nigrostriatal motor system during aging. We examined the effects of perinatal stress (PRS) on the neurochemical, electrophysiological, histological, neuroimaging, and behavioral correlates of striatal motor function in adul...

• Competition for resources often contributes strongly to defining an organism's ecological niche. Endogenous biological rhythms are important adaptations to the temporal dimension of niches, but how other organisms influence such temporal niches has not been much studied, and the role of competition in particular has been even less examined. We in...

Competition for resources often contributes strongly to defining an organism’s ecological niche. Biological rhythms are important adaptations to the temporal dimension of niches, but the role of other organisms in determining such temporal niches have not been much studied, and the role specifically of competition even less so. We investigate how i...

Type-5 metabotropic glutamate receptors (mGlu5) have been implicated in the mechanism of resilience to stress. They form part of the postsynaptic density (PSD), a thickening of the glutamatergic synapse that acts as a multimodal hub for multiple cellular signaling. Perinatal stress in rats triggers alterations that make adult offspring less resilie...

Stress and the circadian systems play a major role in an organism’s adaptation to environmental changes. The adaptive value of the stress system is reactive while that of the circadian system is predictive. Dysfunctions in these two systems may account for many clinically relevant disorders. Despite the evidence that interindividual differences in...

Effect of PRS and sex differences on the expression levels of signaling- and glucose metabolism-related genes in the SCN. Expression of selected genes in the SCN of CONT or PRS rats of both sexes was assayed by Custom Taqman qRT-PCR. Expression levels of each sample were normalized to the average levels in CONT male rats obtained at 15:00 and expre...

The interplay between experiences during critical developmental periods and later adult life is crucial in shaping individual variability in stress coping strategies. Exposure to stressful events in early life has strongly programs an individual's phenotype and adaptive capabilities. Until now, studies on programming and reversal strategies in earl...

S 47445 is a positive modulator of glutamate AMPA-type receptors, possessing neurotrophic and enhancing synaptic plasticity effects as well as pro-cognitive and anti-stress properties. Here, the drug was assessed in the perinatal stress (PRS) rat model, known to have a high predictive validity with monoaminergic antidepressants. The effects of a ch...

In mammals, early adverse experiences, including mother-pup interactions, shape the response of an individual to chronic stress or to stress-related diseases during adult life. This has led to the elaboration of the theory of the developmental origins of health and disease (DOHaD), in particular adult diseases such as cardiovascular and metabolic d...

Oxytocin receptors are known to modulate synaptic transmission and network activity in the hippocampus, but their precise function has been only partially elucidated. Here, we have found that activation of presynaptic oxytocin receptor with the potent agonist, carbetocin, enhanced depolarization-evoked glutamate release in the ventral hippocampus w...

Palatable food is a strong activator of the reward circuitry and may cause addictive behavior leading to eating disorders. How early life events and sex interact in shaping hedonic sensitivity to palatable food is largely unknown. We used prenatally restraint stressed (PRS) rats, which show abnormalities in the reward system and anxious/depressive-...

Prenatal restraint stress (PRS) can induce persisting changes in individual's development. PRS increases anxiety and depression-like behaviors and induces changes in the hypothalamo-pituitary-adrenal (HPA) axis in adult PRS rats after exposure to stress. Since adaptive capabilities also depend on temporal organization and synchronization with the e...

Stress-related events that occur in the perinatal period can permanently change brain and behavior of the developing individual and there is increasing evidence that early-life adversity is a contributing factor in the etiology of drug abuse and mood disorders. Neural adaptations resulting from early-life stress may mediate individual differences i...

Stress-related events that occur in the perinatal period can permanently change brain and behavior of the developing individual and there is increasing evidence that early-life adversity is a contributing factor in the etiology of drug abuse and mood disorders. Neural adaptations resulting from early-life stress may mediate individual differences i...

During the perinatal period, the brain is particularly sensitive to remodelling by environmental factors. Adverse early life experiences, such as stress exposure or sub-optimal maternal care can have long-lasting detrimental consequences for an individual. This phenomenon is often referred to as ‘early-life programming’ and is associated with an in...

Abnormalities of synaptic transmission in the hippocampus represent an integral part of the altered programming triggered by early life stress, which enhances the vulnerability to stress-related disorders in the adult life. Rats exposed to prenatal restraint stress (PRS) develop enduring biochemical and behavioral changes characteristic of an anxio...

In rats, gestational stress has short and long term effect on the stressed mother and on the offspring (PRS: prenatally stressed). Stressed mothers are more anxious and provide less maternal care. These post partum changes in mother’s behaviour are essential for the stress-induced programming of the offspring. In the mother–pup relationship, appeas...

The thymine DNA glycosylase (TDG) is a multifunctional enzyme, which is essential for embryonic development. It mediates the base excision repair (BER) of G:T and G:U DNA mismatches arising from the deamination of 5-methyl cytosine (5-MeC) and cytosine, respectively. Recent studies have pointed at a role of TDG during the active demethylation of 5-...

The use of classical antipsychotic drugs is limited by the occurrence of extrapyramidal motor symptoms, which are caused by dopamine (DA) receptor blockade in the neostriatum. We examined the impact of early life stress on haloperidol-induced catalepsy using the rat model of prenatal restraint stress (PRS). Adult "PRS rats", i.e. the offspring of m...

Chronic hyperactivation of the hypothalamus–pituitary axis is associated with the suppression of reproductive, growth, thyroid and immune functions that may lead to various pathological states. Although many individuals experiencing stressful events do not develop pathologies, stress seems to be a provoking factor in those individuals with particul...

Abnormalities of synaptic transmission and plasticity in the hippocampus represent an integral part of the altered programming triggered by early life stress. Prenatally restraint stressed (PRS) rats develop long-lasting biochemical and behavioral changes, which are the expression of an anxious/depressive-like phenotype. We report here that PRS rat...

Agomelatine is a novel antidepressant acting as an MT1/MT2 melatonin receptor agonist/5-HT2C serotonin receptor antagonist. Because of its peculiar pharmacological profile, this drug caters the potential to correct the abnormalities of circadian rhythms associated with mood disorders, including abnormalities of the sleep/wake cycle. Here, we examin...

article présenté lors du 7. International meeting on metabotropic glutamate receptors ; Taormina (Italie) - (2011-10-02 - 2011-10-07) / Rencontres

The rat model of prenatal restraint stress (PRS) replicates factors that are implicated in the etiology of anxious/depressive disorders. We used this model to test the therapeutic efficacy of agomelatine, a novel antidepressant that behaves as a mixed MT1/MT2 melatonin receptor agonist/5-HT(2c) serotonin receptor antagonist. Adult PRS rats showed b...

We examined the interaction between early life stress and vulnerability to alcohol in female rats exposed to prenatal restraint stress (PRS rats). First we studied the impact of PRS on ethanol preference during adolescence. PRS slightly increased ethanol preference per se, but abolished the effect of social isolation on ethanol preference. We then...

The rat model of prenatal restraint stress (PRS) is particularly valuable to study the mechanisms involved in the pathophysiology of anxiety/depression since adult PRS rats show endocrine and behavioral abnormalities that are corrected by antidepressant medication. We have previously shown that agomelatine chronic treatment reversed the anxiety beh...

Prenatal Restraint Stress (PRS) in rats is a validated model of early stress resulting in permanent behavioral and neurobiological outcomes. Although sexual dimorphism in the effects of PRS has been hypothesized for more than 30 years, few studies in this long period have directly addressed the issue. Our group has uncovered a pronounced gender dif...

Behavioral adaptation to an anxiogenic environment involves the activity of various interconnected limbic regions, such as the amygdala, hippocampus and prefrontal cortex. Prenatal stress (PS) in rats affects the ability to cope with environmental challenges and alters brain plasticity, leading to long-lasting behavioral and neurobiological alterat...

Chronic hyper-activation of the hypothalamus–pituitary axis is associated with the suppression of reproductive, growth, thyroid and immune functions that may lead to various pathological states. Although many individuals experiencing stressful events do not develop pathologies, stress seems to be a provoking factor in those individuals with particu...

Chronic hyper-activation of the hypothalamus-pituitary axis is associated with the suppression of reproductive, growth, thyroid and immune functions that may lead to various pathological states. Although many individuals experiencing stressful events do not develop pathologies, stress seems to be a provoking factor in those individuals with particu...

The aim of this study was to investigate the noradrenergic regulation of mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs) in high responder (HR) and low responder (LR) male rats, an animal model of individual differences in hypothalamo-pituitary-adrenal axis activity and vulnerability to drugs of abuse. The effects of a chronic...

We examined the influence of prenatal stress on alcohol preference in adult female rats exposed to an intense stress. To take into account interindividual variability, the study was conducted in animals categorized as low or high alcohol preferring. After footshock, control high-preferring rats strongly reduced their alcohol consumption; in contras...

The period of adolescence and environmental factors, such as stress, are important in determining ethanol vulnerability in both humans and rats. Ethanol is a powerful activator of the hypothalamic-pituitary-adrenal (HPA) axis but attenuated responses of the HPA axis to ethanol have been described in populations with a high risk of ethanol abuse. In...

Prenatal stress in the rat induces enhanced reactivity of the hypothalamus-pituitary-adrenal (HPA) axis, disturbances in a variety of circadian rhythms and increased anxiety-like behaviour. Such abnormalities parallel those found in human depressed patients. Prenatally stressed (PS) rats could represent, therefore, an interesting animal model for t...

The capacity of an early environmental intervention to normalize the behavioural and immunological dysfunctions produced by a stressed pregnancy was investigated. Pregnant Sprague-Dawley rats underwent three 45-min sessions per day of prenatal restraint stress (PS) on gestation days 11-21, and their offspring were assigned to either an enriched-env...

Human and animal studies indicate that repeated stress during pregnancy can produce long-term biological and behavioural disorders in the offspring. In contrast, although maternal stress is supposed to induce an increase of maternal anxiety, few studies have been conducted to demonstrate it. Therefore, in the present study we examined the emotional...

We examined the influence of prenatal stress on 3,4-methylenedioxymethamphetamine (MDMA, 5 mg/kg p.o.) pharmacokinetics in adolescent female SD rats (30 days). Our results indicate that the metabolic rate of MDMA was higher in the prenatal stress group than in the control group. Moreover, MDMA-induced motor alterations were increased in prenatally...

Prenatal stress (PS) can produce profound and long-lasting perturbations of individual adaptive capacities, which in turn can result in an increased proneness to behavioural disorders. Indeed, in PS rats there is evidence of impaired social play behaviour, disturbances in a variety of circadian rhythms, enhanced anxiety and increased hypothalamic-p...

Prenatal stress (PS) can produce profound and long-lasting perturbations of individual adaptive capacities, which in turn can result in an increased proneness to behavioural disorders. Indeed, in PS rats there is evidence of impaired social play behaviour, disturbances in a variety of circadian rhythms, enhanced anxiety and increased hypothalamic-p...

Prenatally-stressed (PS) rats are characterized by a general impairment of the hypothalamo-pituitary-adrenal (HPA) axis and sleep disturbances indicating that this model has face validity with some clinical features observed in a subpopulation of depressed patients. The prolonged corticosterone secretion shown by PS rats in response to stress was p...

In multiparous rodents, a naturally occurring variation in degree of exposure to sex steroids during the prenatal phase of sexual differentiation derives from the in-utero proximity to opposite sex foetuses. So far, the studies on intrauterine position (IUP) phenomenon have mostly focused on traits relating to reproduction and behaviour, while its...

Epidemiological research has emphasized that adolescence is associated with some temperamental and behavioral traits that are typical of this age and that might substantially contribute to both psychological and psychobiological vulnerability. The contribution of the important developmental rearrangements in neurobiological and neuroendocrinologica...

We have shown that prenatal restraint stress (PNRS) induces higher levels of anxiety, greater vulnerability to drugs, a phase advance in the circadian rhythm of locomotor activity and an increase in the paradoxical sleep in adult rats. These behavioral effects result from permanent modifications to the functioning of the brain, particularly in the...

In spite of the increasing evidence concerning its neurotoxicity, young human individuals are often involved in the recreational use of amphetamine-type stimulants such as 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy"). A study aimed to investigate short- and long-term consequences of a repeated and intermittent MDMA administration (0, 5 or...

Although final brain size and the number of available neurons and axons appear to be established early in infancy, plasticity of the brain continues during adolescence through an integrated process of overproduction and elimination of synapses and receptors. In addition, hormonal levels change dramatically during this period, as a result of the ons...

Human adolescence is mainly characterised by an elevated number of psychological, biological and behavioural changes. This rapid as well as challenging change in the "inner state" during adolescence in humans seems to share a number of similarities with the age-dependent alteration of the normal and "linear" development in other mammalian species....

This review presents the experimental approaches more widely used in animal models to investigate possible strategies aimed to stimulate plasticity in the nervous system and possibly to increase spontaneous recovery from functional/neurological diseases such as neonatal anoxia. Methods used in laboratory rodents are briefly described. Attention is...

In rodents, beside basic sex differences, a certain degree of within-gender phenotypic variation can also be provided in utero by hormones from adjacent fetuses. We investigated novelty-seeking behavior in two groups of male and female mice from know intrauterine position: 2M (between males) and 0M (between females). Subjects were assessed during p...

Riassunto. - Nell'uomo, la fase adolescenziale risulta associata a un elevato numero di cambiamenti di tipo psicologico, biologico e comportamentale. Questa repentina quanto tumultuosa serie di sconvolgimenti dell' "ambiente interno" dell'organismo adolescente sembra avere stretti correlati filogenetici con quanto avviene in mammiferi appartenenti...