Impaired Interleukin-1β and c-Fos Expression in the Hippocampus Is Associated with a Spatial Memory Deficit in P2X7 Receptor-Deficient Mice

Recent evidence suggests that interleukin-1β (IL-1β), which was originally identified as a proinflammatory cytokine, is also required in the brain for memory processes. We have previously shown that IL-1β synthesis in the hippocampus is dependent on P2X7 receptor (P2X7R), which is an ionotropic receptor of ATP. To substantiate the role of P2X7R in both brain IL-1β expression and memory processes, we examined the induction of IL-1β mRNA expression in the hippocampus of wild-type (WT) and homozygous P2X7 receptor knockout mice (P2X7R−/−) following a spatial memory task. The spatial recognition task induced both IL-1β mRNA expression and c-Fos protein activation in the hippocampus of WT but not of P2X7R−/− mice. Remarkably, P2X7R−/− mice displayed spatial memory impairment in a hippocampal-dependant task, while their performances in an object recognition task were unaltered. Taken together, our results show that P2X7R plays a critical role in spatial memory processes and the associated hippocampal IL-1β mRNA synthesis and c-Fos activation

Sugar Overconsumption during Adolescence Selectively Alters Motivation and Reward Function in Adult Rats

International audienceBACKGROUND:There has been a dramatic escalation in sugar intake in the last few decades, most strikingly observed in the adolescent population. Sugar overconsumption has been associated with several adverse health consequences, including obesity and diabetes. Very little is known, however, about the impact of sugar overconsumption on mental health in general, and on reward-related behavioral disorders in particular. This study examined in rats the effects of unlimited access to sucrose during adolescence on the motivation for natural and pharmacological rewards in adulthood.METHODOLOGY/PRINCIPAL FINDINGS:Adolescent rats had free access to 5% sucrose or water from postnatal day 30 to 46. The control group had access to water only. In adulthood, rats were tested for self-administration of saccharin (sweet), maltodextrin (non-sweet), and cocaine (a potent drug of abuse) using fixed- and progressive-ratio schedules, and a concentration-response curve for each substance. Adult rats, exposed or not exposed to sucrose, were tested for saccharin self-administration later in life to verify the specificity of adolescence for the sugar effects. Sugar overconsumption during adolescence, but not during adulthood, reduced the subsequent motivation for saccharin and maltodextrin, but not cocaine. This selective decrease in motivation is more likely due to changes in brain reward processing than changes in gustatory perception.CONCLUSIONS/SIGNIFICANCE:Sugar overconsumption induces a developmental stage-specific chronic depression in reward processing that may contribute to an increase in the vulnerability to reward-related psychiatric disorders

Pregnenolone sulfate increases hippocampal acetylcholine release and spatial recognition.

International audienceThe pregnenolone sulfate is a neurosteroid with promnesic properties. Recently, a correlation between endogenous levels of pregnenolone sulfate in the hippocampus and performance in a spatial memory task has been reported in aged rats. Cholinergic transmission is known to modulate memory processes and to be altered with age. In the present experiment we investigated the effect of increasing doses of pregnenolone sulfate on hippocampal acetylcholine release. Our results show that intracerebroventricular administrations of this neurosteroid induced a dose-dependent increase in acetylcholine release. Administration of 12 and 48 nmol of pregnenolone sulfate induced a short lasting (20 min) enhancement of acetylcholine output with a maximum around 120% over baseline and the administration of 96 and 192 nmol doses induced a long-lasting (80 min) increase that peaked around 300% over baseline. In a second experiment we have observed that the 12 nmol dose enhanced spatial memory performance, whereas the 192 nmol dose was inefficient. These results are consistent with previous work suggesting that, a modest increase in acetylcholine release facilitates memory processes, while elevation beyond an optimal level is ineffective. Nevertheless, neurosteroids may be of value for reinforcing depressed cholinergic transmission in certain age-related memory disorders

The effect of restraint stress on paradoxical sleep is influenced by the circadian cycle

International audienceIt is well known that the physiological impact imposed by events or behaviors displayed during the waking period determines the way organisms sleep. Among the situations known to affect sleep both in its duration and quality, stress has been widely studied and it is now admitted that its effects on sleep architecture depend on several factors specific to the stressor or the individual itself. Although numerous reports have highlighted the prominent role of the circadian cycle in the physiological, endocrine and behavioral consequences of restraint stress, a possible circadian influence in the effects of stress on the sleep-wake cycle has never been studied. Thus the present study was designed to compare the effects on sleep of a 1 h-lasting restraint stress applied at light onset to those observed after the same stressor was applied at light offset. We report that in both conditions stress induced a marked paradoxical sleep increase, whereas wakefulness displayed a moderate decrease and slow wave sleep a moderate augmentation. Although the effects of stress at lights on were of similar magnitude than those of stress at lights off, important differences in the sleep rebound latencies were observed: whatever the time of day the stress was applied, its effects on sleep always occurred during the dark period. This result thus shows that restraint stress could be efficiently used to study the interaction between the circadian and homeostatic components of sleep regulation

Impact of an acute exposure to ethanol on the oxidative stress status in the hippocampus of prenatal restraint stress adolescent male rats

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The early life nutritional environment and early life stress as potential pathways towards the metabolic syndrome in mid-life? A lifecourse analysis using the 1958 British Birth cohort

Background: Lifecourse studies suggest that the metabolic syndrome (MetS) may be rooted in the early life environment. This study aims to examine the pathways linking early nutritional and psychosocial exposures and the presence of MetS in midlife. Methods: Data are from the National Child Development Study including individuals born during 1 week in 1958 in Great Britain and followed-up until now. MetS was defined based on the National Cholesterol Education Program Adult Treatment Panel III classification. Mother’s pre-pregnancy body mass index (BMI) was used as a proxy of the early nutritional environment and Adverse Childhood Experiences (ACE) as a proxy for early psychosocial stress. Socioeconomic characteristics, pregnancy and birth conditions were extracted as potential confounders. Adult health behaviors, BMI, socioeconomic environment and psychological state were considered as mediating variables. Multivariate models were performed by including variables sequentially taking a lifecourse approach. Results: 37.5 % of men and 19.8 % of women had MetS. Participants with an obese/overweight mother presented a higher risk of MetS than those whose mother had a normal pre-pregnancy BMI. Men exposed to two ACE or more, and women exposed to one ACE, were more at risk of MetS compared to unexposed individuals. After including confounders and mediators, mother’s pre-pregnancy BMI was still associated with MetS in midlife but the association was weakened after including participant’s adult BMI. ACE was no longer associated with MetS after including confounders in models. Conclusions: The early nutritional environment, represented by mother’s pre-pregnancy BMI, was associated with the risk of MetS in midlife. An important mechanism involves a mother-to-child BMI transmission, independent of birth or perinatal conditions, socioeconomic characteristics and health behaviors over the lifecourse. However this mechanism is not sufficient for explaining the influence of mother’s pre-pregnancy BMI which implies the need to further explore other mechanisms in particular the role of genetics and early nutritional environment. ACE is not independently associated with MetS. However, other early life stressful events such as emergency caesarean deliveries and poor socioeconomic status during childhood may contribute as determinants of MetSAgence Nationale de la Recherche/[ANR-12-DSSA-0004]/ANR/FranciaFond Français pour l’Alimentation et la Santé/[12 D-25]/FFAS/FranciaUCR::Vicerrectoría de Docencia::Salud::Facultad de Odontologí

Effect of prenatal stress on alcohol preference and sensitivity to chronic alcohol exposure in male rats

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Effect of prenatal stress on alcohol preference and sensitivity to chronic alcohol exposure in male rats

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