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Aversive amygdala-dependent memory and amygdala activation. (A) Odorized water intake did not differ between groups on acquisition day. (B) Aversive memory was assessed 3 days after the acquisition trial. All groups showed an avoidance of the odorized water however, the strength of the avoidance was greater in group HF (black bar). *p < 0.01, #p = 0.09 (significant one-way ANOVA followed by Fisher’s post hoc). (C) Rats in the group HF showed increase circulating corticosterone levels 90 min after lithium chloride (LiCl) injection compared to groups C (white bar) and HF-C (striped bar). *p < 0.05 when compared to both C and HF-C groups (significant one-way ANOVA followed by Fisher’s post hoc). (D) Rats in group HF showed a higher number of c-Fos positive cells in the basolateral amygdala (BLA) 90 min after LiCl injection than groups C and HF-C. *p < 0.05 (significant one-way ANOVA followed by Fisher’s post hoc). Representative photomicrographs of c-Fos immunoreactivity in the BLA for groups C, HF and HF-C.
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In addition to metabolic and cardiovascular disorders, obesity is associated with adverse cognitive and emotional outcomes. Its growing prevalence in adolescents is particularly alarming since this is a period of ongoing maturation for brain structures (including the hippocampus and amygdala) and for the hypothalamic-pituitary-adrenal (HPA) stress...
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The negative impact of obesity on neurocognitive functioning is an issue of increasing clinical interest. Over the last decade, a number of studies have analyzed the influence of high-fat diets (HFDs) on cognitive performance, particularly in adolescent individuals. Different approaches, including behavioral, neurochemical, electrophysiological and...
Citations
... Studies in rodents have shown that the consumption of high-fat and high-sucrose diets during adolescence can have significant detrimental effects on hippocampal functions, such as neurogenesis and spatial memory [20,46,6]. Recent studies by Mota et al. [45] reported that high-fat, high-sugar diets compromise hippocampal function, including neurogenesis and spatial memory in aged rats, implying that vulnerability to diet-induced cognitive decline is not limited to early development, but extends into older age. Nevertheless, some studies have suggested that particular adverse factors during prenatal and early postnatal periods, such as consumption of a high-fat diet, might confer a resiliency effect against other adverse factors, such as early life stress, possibly due to the protective nature of fats. ...
... Similarly, a high-fat diet is associated with impaired dopaminergic signaling in the prefrontal cortex [40,49] and alterations in cognition and memory flexibility in rats and mice [14,27,39]. In the hippocampus, exposure to a Western diet starting after weaning and continuing until adulthood can lead to impaired hippocampal-dependent behavioral tasks, increased levels of pro-inflammatory cytokines, and reduced neurogenesis [6]. The effect of HF diets on spatial memory varies significantly with the period of exposure, whether during gestation and lactation, after weaning, or throughout life, suggesting that the timing and duration of exposure to such diets are critical factors in determining their effects on brain health and function [28]. ...
... Adolescence is a vulnerable period for the detrimental cognitive effects of WD in humans (Ruiz et al., 2020;[56]). In rodents, early adolescence after weaning is a neurodevelopmental stage that is susceptible to the harmful effects of high-fat and high-sucrose diets [5,51,6]. Our study examined how HFS diets impact cognitive function and brain metabolism, in line with the Developmental Origins of Health and Disease (DOHAD) hypothesis. ...
... Several studies have investigated the effects of a high fat diet on neurobehavioral and endocrine processes in male and female rats of different ages [16][17][18][19][20]. The findings of these studies revealed that significant cognitive deficits and reproductive dysfunction are strongly associated with hyper-reactivity of the HPA axis and hypogonadism. ...
... Results are considered significant at p < 0.05. *p < 0.05, **p < 0.01, ***p < 0.001 compared with the control group high-fat diet, adolescent, and adult DIO rats, as indicated by anxiety-like behaviors in behavioral tests and altered expression of genes involved in HPA axis regulation [16,46,47]. Notably, most experimental groups showed significantly up-regulated hypothalamic expression of CRH but down-regulated expressions of CRHR1 and CRHR2 in the pituitary gland. ...
Purpose
Diet-related factors are of great significance in the regulation of hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonad (HPG) axes. In this study, we aimed to investigate the effects of chronic exposure to a high fat diet (HFD), fructose or sucralose on the endocrine functions.
Methods
Male, Sprague-Dawley rats received a normal chow diet, HFD, 10% fructose or 0.02% sucralose for 10 weeks. Behavioral changes were assessed by open field (OFT) and elevated plus-maze (EPM) tests at week 8. H&E staining was used to observe pathological changes in adrenal cortex, testis and perirenal adipose tissue. Serum hormone concentrations were quantified via enzyme-linked immunosorbent assay (ELISA). The mRNA expression levels of genes along the HPA and HPG axes were determined using real-time PCR.
Results
All types of dietary interventions increased body weight and disturbed metabolic homeostasis, with anxiogenic phenotype in behavioral tests and damage to cell morphology of adrenal cortex and testis being observed. Along the HPA axis, significantly increased corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and corticosterone (CORT) concentrations were observed in the HFD or 0.02% sucralose group. For HPG axis, gonadotropin-releasing hormone (GnRH) and estradiol (E2) concentrations were significantly increased in all dietary intervention groups, while decreased concentrations of follicle-stimulating hormone (FSH) and testosterone (T) were also detected. Moreover, transcriptional profiles of genes involved in the synthesis of hormones and corresponding hormone receptors were significantly altered.
Conclusion
Long-term consumption of HFD, fructose or sucralose manifested deleterious effects on endocrine system and resulted in the dysregulation of HPA and HPG axes.
... Accurately measuring caloric intake in individual animals necessitated the methodological decision to singly house rats, but this could also have altered the vulnerability of the HPC to dietary insults or other stressors. Although in the present work WD-induced memory impairments persisted despite a healthy diet intervention in adulthood, some previous studies have found that a standard/ healthy diet intervention rescues memory deficits in other WD models (Boitard et al., 2016;Hao et al., 2016;Nicolas et al., 2022;Sobesky et al., 2014;Tran and Westbrook, 2017). Differences in type of WD (e.g., types of foods, macronutrient profiles), duration of exposure to a given WD and standard/healthy diet, and age during exposure could be related to the discrepant findings. ...
Western diet (WD) consumption during early life developmental periods is associated with impaired memory function, particularly for hippocampus (HPC)-dependent processes. We developed an early life WD rodent model associated with long-lasting HPC dysfunction to investigate the neurobiological mechanisms mediating these effects. Rats received either a cafeteria-style WD (ad libitum access to various high-fat/high-sugar foods; CAF) or standard healthy chow (CTL) during the juvenile and adolescent stages (postnatal days 26–56). Behavioral and metabolic assessments were performed both before and after a healthy diet intervention period beginning at early adulthood. Results revealed HPC-dependent contextual episodic memory impairments in CAF rats that persisted despite the healthy diet intervention. Given that dysregulated HPC acetylcholine (ACh) signaling is associated with memory impairments in humans and animal models, we examined protein markers of ACh tone in the dorsal HPC (HPCd) in CAF and CTL rats. Results revealed significantly lower protein levels of vesicular ACh transporter in the HPCd of CAF vs. CTL rats, indicating chronically reduced ACh tone. Using intensity-based ACh sensing fluorescent reporter (iAChSnFr) in vivo fiber photometry targeting the HPCd, we next revealed that ACh release during object-contextual novelty recognition was highly predictive of memory performance and was disrupted in CAF vs. CTL rats. Neuropharmacological results showed that alpha 7 nicotinic ACh receptor agonist infusion in the HPCd during training rescued memory deficits in CAF rats. Overall, these findings reveal a functional connection linking early life WD intake with long-lasting dysregulation of HPC ACh signaling, thereby identifying an underlying mechanism for WD-associated memory impairments.
... Dentate gyrus (DG) is one of the two critical regions in the hippocampus (DG and CA1-3) those are involved in spatial learning and memory in mammals by encoding and processing spatial information to the hippocampus [25,14]. Moreover, convincing evidences indicate the impairment of spatial memory in rodent models of DIO, manifested by morphological damage, inflammation, and a decrease in neurogenesis in the DG region of the hippocampus [4,5,10]. Therefore, these reports strongly support the notion that the dysregulation in DG are crucial in spatial learning and memory deficits in DIO. ...
... The overconsumption of energy-dense, palatable foods is one of the major reasons for obesity, and evidence indicates that an energy-dense diet could be more harmful for the adolescent consumers than the adults. Overconsumption of high fat diet throughout adolescence, but not during adulthood, is associated with changes in spatial and emotional memory [5,26]. Experimental models of DIO rats have already been used in various studies to investigate molecular mechanisms mediating cognition and memory [22,9,7] and our results are in line with the previous conclusions that consuming fat-rich diet is linked with spatial learning and memory deficit in rats when induced from young (4 weeks) to adult (12 weeks). ...
Obesity has been linked with the impairment of spatial memory and synaptic plasticity but the molecular mechanisms remained unidentified. Since glutamatergic transmission and NMDA receptor neural pathways in hippocampal dentate gyrus (DG) are essential in the learning and memory, we aimed to investigate glutamate (Glu) and NMDA receptor signaling of DG in spatial learning and memory in diet-induced obesity (DIO) rats. Spatial learning and memory were assessed via Morris water maze (MWM) test on control (Ctr) and DIO rats. Extracellular concentration of Glu in the DG was determined using in vivo microdialysis and HPLC. The protein expressions of NMDA receptor subunit 2B (NR2B), brain-derived neurotrophic factor (BDNF), the activation of calcium/calmodulin-dependent kinase II (CaMKII) and cAMP-response-element-binding protein (CREB) in the DG were observed by western blot. Spatial learning and memory were impaired in DIO rats compared to those of Ctr. NR2B expression was increased, while BDNF expression and CaMKII and CREB activation were decreased in DG of DIO rats. Extracellular concentration of Glu was increased in Ctr on the 3rd and 4th days of the MWM test, but significant further increment was observed in DIO rats. Microinjection of an NMDA antagonist (MK-801) into the DG reversed spatial learning and memory impairment. Such effects were accompanied by greater BDNF expression and CaMKII/CREB activation in the DG of DIO rats. In conclusion, the enhancement of Glu-NMDA receptor transmission in the hippocampal DG contributes to the impairment of spatial learning and memory in DIO rats, maybe via the modulation of CaMKII-CREB-BDNF signaling pathway.
... For this reason, after 8 weeks of exposure to HFSD, rats were switched to normal chow for several days before being tested for excessive motivation or resistance to punishment. This may have contributed to the lack of effects of HFSD since other studies have found that some of the deleterious effects of obesogenic diets tend to disappear upon discontinuation (Boitard et al., 2016;Carlin et al., 2016;Rabasa et al., 2016). However, other studies have found long-lasting effects of obesogenic diets on motivation (Garman et al., 2021;Reichelt et al., 2016;Tracy et al., 2015;Vendruscolo et al., 2010). ...
Exposure to food rich in fat and sugar (High Fat and Sugar Diet, HFSD) is believed to induce behavioral and neurobiological changes that would produce addiction-like behavior and increase the risks of obesity and overweight. Studies in rodents have led to conflicting results suggesting that several factors such as sex and age of exposure contribute to the development of maladaptive behavior towards food. In addition, it is not clear whether the effects of exposure to HFSD persist after its discontinuation which would indicate long-term risk to develop addiction-like behavior. In this study, we investigated the persistent effects of an intermittent 8-week exposure to HFSD in male and female rats as a function of age of exposure (adult and adolescent). We found that intermittent exposure to HFSD did not alter body weight, but it affected consumption of standard food during the time of exposure in all groups. In addition, in adults, HFSD produced a decrease in the initial baseline responding in FR1 schedules that persisted for 4 weeks in males but not in female rats. However, we found that exposure to HFSD did not affect resistance to punishment measured by progressive shock strength (PSS) break points or motivation for food measured by progressive-ratio break points regardless of sex or age of exposure. Altogether, these results do not provide support to the hypothesis that intermittent exposure to HFSD produce persistent increases in the vulnerability to develop addiction-like behaviors towards palatable food.
... However, these mice were returned to a chow diet for 5 weeks prior to behavioral testing, and it is possible that this diet switch ameliorated the effects of the high-fat diet on choice behavior. Indeed, several studies have observed improvements in various cognitive functions in rodents switched from HFHS diets to regular chow (Sobesky et al., 2014;Boitard et al., 2016;Tran and Westbrook, 2017;Kendig et al., 2018;McLean et al., 2018;Altherr et al., 2021). Nevertheless, these few studies indicate that it is not excess weight per se that drove the changes in cue-driven choice. ...
Our modern environment is said to be obesogenic, promoting the consumption of calorically dense foods and reducing energy expenditure. One factor thought to drive excess energy intake is the abundance of cues signaling the availability of highly palatable foods. Indeed, these cues exert powerful influences over food-related decision-making. Although obesity is associated with changes to several cognitive domains, the specific role of cues in producing this shift and on decision-making more generally, remains poorly understood. Here we review the literature examining how obesity and palatable diets affect the ability of Pavlovian cues to influence instrumental food-seeking behaviors by examining rodent and human studies incorporating Pavlovian-instrumental transfer (PIT) protocols. There are two types of PIT: (a) general PIT that tests whether cues can energize actions elicited in the pursuit of food generally, and (b) specific PIT which tests whether cues can elicit an action that earns a specific food outcome when faced with a choice. Both types of PIT have been shown to be vulnerable to alterations as a result of changes to diet and obesity. However, effects appear to be driven less by increases in body fat and more by palatable diet exposure per se . We discuss the limitations and implications of the current findings. The challenges for future research are to uncover the mechanisms underlying these alterations to PIT, which appear unrelated to excess weight itself, and to better model the complex determinants of food choice in humans.
... Patel & Issac (2019) denoted that insufficiency of Protein-energy among children is liable for deficit in motor development. Research studies have summarized that unbalanced consumption of food which contains high fat and sugar is responsible for alteration of brain regions which are associated with learning, memory and reward (Boitard et al., 2016;Gainey et al., 2016). This indicates that balanced consumption of Macro-nutrients during adolescence phase of life, act as critical parameter for attainment of higher order scholastic performance. ...
Background: - Diet and nutrition is the foremost pivotal component during childhood and adolescence stage, as deficiency of which may cause rudimentary physiological, motor, and cognitive development. Hence, a balanced diet (which comprised of all vital nutrients and minerals) is of prime importance during growth years so as to achieve optimum degree of cognitive and scholastic performance.
Objective:-The prime rationale of the present study is to analyze the inter-relationship between different dietary Macro-nutrients (Energy, Carbohydrate, protein, and Fats) and Micro-nutrients (Calcium, Phosphorus, and Iron) with Scholastic Achievement of adolescents.
Method: A sample of 164 Government school students from Class 11th and 12th has been selected from Delhi, India using random sampling procedure. Correlational research design has been used for this study.
Result: The obtained findings established that significant positive association occurs between dietary Macro-nutrients (Energy, Carbohydrate, protein, and Fats), Micro-nutrients (Calcium, Phosphorus, and Iron) and Scholastic achievement of students. Regression analysis also represented that dimension “Energy” of Macro-nutrient is act as notable predictor of Scholastic Achievement.
Conclusion: Dietary Macro-nutrients (Energy, Carbohydrate, protein, and Fats) and Micro- nutrients (Calcium, Phosphorus, and Iron) play significant role for the acquiring higher Scholastic performance among adolescents.
... Dans certain cas, il a été montré que des perturbations de la motivation des animaux persistaient 1 mois après l'arrêt d'un régime hyperpalatable (Arcego et al., 2020), ou des dysfonctionnements synaptiques dans l'hippocampe plusieurs mois après l'arrêt (Wang et al., 2015). Dans d'autres études, il a été observé un retour à la normale des comportements alimentaires des rats ou des altérations neurobiologiques 1 mois après l'arrêt du régime (Boitard et al., 2016;Carlin et al., 2016;Rabasa et al., 2016). De ce fait, la question de la persistance d'un effet par la nourriture hyperpalatable n'a pas encore été résolue. ...
... For this after 8 weeks of exposure to HFSD, rats were switched to normal chow for several days before being tested for excessive motivation or resistance to punishment. This may have contributed to the lack of effects of HFSD as several studies have found that the some of the deleterious effects of obesogenic diets tend to disappear upon discontinuation (Boitard et al. 2016;Carlin et al. 2016;Rabasa et al. 2016). We based our protocol of exposure on the one used by Rossetti et al. (Rossetti et al. 2014) with the only notable difference that we discontinued HFSD diet several days before the beginning of operant training. ...
L’addiction aux drogues est considérée comme un trouble psychiatrique chronique caractérisé par une recherche et une prise compulsive de drogue et par un fort taux de récidive. Mes travaux de thèse s’organisent en 2 axes. Dans le premier axe, nous avons développé une nouvelle procédure comportementale pour étudier le comportement compulsif vis-à-vis de la nourriture qui prenne en considération le niveau de résistance individuel (article1). Pour la suite, avec cette procédure, nous avons réalisé une investigation comportementale sur l’influence d’un régime riche en graisse et en sucre sur le développement d’une addiction à la nourriture. En effet, l’une des questions encore non résolues est de savoir si les effets observés suite à une exposition à un régime palatable persistent ou disparaissent après un certain temps. De plus, nous avons cherché à savoir si le sexe de l’animal ou l’âge d’exposition pouvait être des facteurs de vulnérabilité. Les résultats obtenus montrent que l’exposition chronique à de nourriture riche en sucre et en graisse n’a pas d’effet persistant sur la motivation et la résistance à la punition des animaux et que ni le sexe ni l’âge n’avaient d’influence majeure sur la compulsivité à consommer une récompense sucrée (article 2).Dans le second axe, nous avons étudié si le métabolisme du cholestérol cérébral pouvait représenter une nouvelle cible thérapeutique pour prévenir la rechute et traiter l’addiction. Dans ce but, nous avons modulé le métabolisme cérébral du cholestérol grâce à des vecteur viraux au sein de structures impliquées dans l'addiction et étudier les effets bénéfiques potentiels sur les comportements d’addiction (article 3). Ainsi, après des sessions d’auto-administration de cocaïne, nous avons surexprimé la cholestérol hydroxylase (gène CYP46A1), l’enzyme de dégradation du cholestérol principalement trouvée dans le cerveau et étudié les effets de cette modulation sur la rechute. Les résultats ont montré que la surexpression de CYP46A1 dans le striatum dorsal (Dst), pendant la période d’abstinence, a réduit la recherche de drogue chez des rats addicts. La surexpression de CYP46A1 dans le cortex cingulaire antérieur et le noyau accumbens n’a pas eu d’effet. Des investigations supplémentaires ont montré que la surexpression de CYP46A1 dans le DSt ne modifie pas le comportement de recherche d’une récompense naturelle ou dans d’autres comportements pendant la phase de consommation de la drogue, à savoir la résistance à la punition et la motivation. Pour cela, le virus a été injecté avant la première exposition à la drogue. Ces observations indiquent que le métabolisme du cholestérol joue un rôle dans l’addiction et que la manipulation de cette voie métabolique pendant une période d’abstinence, spécifiquement dans le DSt, pourrait avoir des effets bénéfiques pour prévenir la rechute. Ces résultats montrent que le métabolisme du cholestérol, spécifiquement dans le DSt, représente une potentielle nouvelle cible thérapeutique pour prévenir la rechute et traiter l’addiction.
... This point will be further explored later. Anyway, it is important to note here that some attempts have been made at establishing a causal link as to how a high-fat diet, such as eating junk foods, could give rise to cerebral dysfunction in adolescents, and whether effects on brain function are permanent or reversible [39]. It is also evident that, in urban adolescents, depression is associated with junk food [40]. ...
Recent data show that young people, mainly due to the pressure of some risk factors or due to disrupted interpersonal relationships, utilise greater reward value and display greater sensitivity to the reinforcing properties of “pleasurable stimuli”, specifically in those situations in which an enhanced dopamine release is present. Alcoholic beverages, foods rich in sugar and fat, and illicit drug use are pleasurable feelings associated with rewards. Research shows that there is a link between substance abuse and obesity in brain functioning. Still, alcohol excess is central in leading to obesity and obesity-related morbidities, such as hepatic steatosis, mainly when associated with illicit drug dependence and negative eating behaviours in young people. It is ascertained that long-term drinking causes mental damage, similarly to drug abuse, but also affects liver function. Indeed, beyond the pharmacokinetic interactions of alcohol with drugs, occurring in the liver due to the same metabolic enzymes, there are also pharmacodynamic interactions of both substances in the CNS. To complicate matters, an important noxious effect of junk foods consists of inducing obesity and obesity-related NAFLD. In this review, we focus on some key mechanisms underlying the impact of these addictions on the liver, as well as those on the CNS.
... On the other hand, the prefrontal cortex and the hippocampus are involved in learning and memory acquisition, consolidation, and retrieval [24]. In this regard, long-term consumption of WD in rodents has been associated with alterations in the prefrontal cortex and the hippocampus leading to memory impairment in adulthood [3,25]. Perinatal exposure to WD impairs hippocampal-dependent spatial memory tasks associated with overexpression of hippocampal pro-inflammatory cytokines and decreased neurogenesis [25] and activates neuronal signalling pathways leading to adverse effects in the hippocampus and the prefrontal cortex mediated by mitochondrial dysfunction impairing neuronal energy metabolism and increasing ROS (reactive oxygen species) levels [26,27]. ...
... In this regard, long-term consumption of WD in rodents has been associated with alterations in the prefrontal cortex and the hippocampus leading to memory impairment in adulthood [3,25]. Perinatal exposure to WD impairs hippocampal-dependent spatial memory tasks associated with overexpression of hippocampal pro-inflammatory cytokines and decreased neurogenesis [25] and activates neuronal signalling pathways leading to adverse effects in the hippocampus and the prefrontal cortex mediated by mitochondrial dysfunction impairing neuronal energy metabolism and increasing ROS (reactive oxygen species) levels [26,27]. Moreover, several studies report sex differences in spatial learning and memory, both in rodents and humans [27][28][29] related with a sex-specific activation of different brain regions like the hippocampus [28,30]. ...
Prolonged daily intake of Western-type diet rich in saturated fats and sugars, and exposure to early life stress have been independently linked to impaired neurodevelopment and behaviour in animal models. However, sex-specific effects of both environmental factors combined on spatial learning and memory, behavioural flexibility, and brain oxidative capacity have still not been addressed. The current study aimed to evaluate the impact of maternal and postnatal exposure to a high-fat and high-sugar diet (HFS), and exposure to early life stress by maternal separation in adult male and female Wistar rats. For this purpose, spatial learning and memory and behavioural flexibility were evaluated in the Morris water maze, and regional brain oxidative capacity and oxidative stress levels were measured in the hippocampus and medial prefrontal cortex. Spatial memory, regional brain oxidative metabolism, and levels of oxidative stress differed between females and males, suggesting sexual dimorphism in the effects of a HFS diet and early life stress. Males fed the HFS diet performed better than all other experimental groups independently of early life stress exposure. However, behavioural flexibility evaluated in the spatial reversal leaning task was impaired in males fed the HFS diet. In addition, exposure to maternal separation or the HFS diet increased the metabolic capacity of the prefrontal cortex and dorsal hippocampus in males and females. Levels of oxidative stress measured in the latter brain regions were also increased in groups fed the HFS diet, but maternal separation seemed to dampen regional brain oxidative stress levels. Therefore, these results suggest a compensatory effect resulting from the interaction between prolonged exposure to a HFS diet and early life stress.
