Effect of Probiotic Lacticaseibacillus rhamnosus LB1.5 on Anxiety-like Behavior, Neuroprotection and Neuroinflammation Markers of Male Mice Fed a High-Fat Diet.

Probiotic supplementation has been identified as a potential target to reduce inflammatory mediators associated with obesity. Therefore, this study assessed the effect of probiotic Lacticaseibacillus rhamnosus LB1.5 on anxiety-like behavior, gene expression in the prefrontal cortex, and neuroinflammation in the cerebral cortex and hippocampus of male mice fed a high-fat diet. Mice aged 21 days were divided into four groups: control (CONT), control plus probiotic (CONT + PROB), high-fat diet (HFD), and high-fat diet plus probiotic (HFD + PROB), and fed for 13 weeks. The probiotic Lact. rhamnosus 1.5 (3.1 × 108 CFU/mL, derived from raw buffalo milk) was administered by gavage three times a week. Probiotic supplementation provided an anxiolytic effect in CONT and HFD. The IL-6 showed lower levels after probiotic supplementation in the HFD. Regarding immunoreactivity for GFAP in the cerebral cortex, we demonstrated that animals HFD-fed had a reduction in cells number compared to CONT. In the hippocampus, we found an interaction between diet and supplementation, as well as an effect of probiotic supplementation. A higher number of Th positive cells was observed in the cerebral cortex in mice fed HFD. Lact. rhamnosus LB1.5 supplementation decreased serum IL-6 levels in HFD-fed mice and promoted a reduction in anxiety-like behavior.

Effects of omega-3 supplementation on anxiety-like behaviors and neuroinflammation in Wistar rats following cafeteria diet-induced obesity.

ABSTRACTObjetives: Omega-3 (n3) fatty acids have been studied as an option to alleviate the harmful effects of obesity. However, its role in obesity-related behavioral changes is still controversial. This study aimed to evaluate the effects of n3 on behavior and neuroinflammation in obese animals. Methods: Male Wistar rats were divided into four groups: control diet (CT), CT+n3, cafeteria diet (CAF), and CAF+n3. Diet was administered for 13 weeks, and n3 was supplemented during the last 5 weeks. Metabolic and biochemical parameters were evaluated, as well as anxiety-like behaviors. Immunoblots were conducted in the animals' cerebral cortex and hippocampus to assess changes in neuroinflammatory markers.Results: CAF-fed animals showed higher weight gain, visceral adiposity, fasting glucose, total cholesterol, triglycerides, and insulin levels, and n3 improved the lipid profile and restored insulin sensitivity. CAF-fed rats showed anxiety-like behaviors in the open field and light-dark box tasks but not in the contextual aversive conditioning. Omega-3 did not exert any effect on these behaviors. Regarding neuroinflammation, diet and supplementation acted in a region-specific manner. In the hippocampus, CAF reduced claudin-5 expression with no effect of n3, indicating a brain-blood barrier disruption following CAF. Furthermore, in the hippocampus, the glial fibrillary acidic protein (GFAP) and toll-like receptor 4 (TLR-4) were reduced in treated obese animals. However, n3 could not reverse the TLR-4 expression increase in the cerebral cortex.Discussion: Although n3 may protect against some neuroinflammatory manifestations in the hippocampus, it does not seem sufficient to reverse the increase in anxiolytic manifestations caused by CAF.

Effects of different maternal diets on adipose tissue inflammation and liver tissue oxidative stress in dams and their female offspring.

Pregnancy and lactation are important stages of fetal development. Therefore, this study investigated how different maternal diets offered during gestation and lactation periods affect adipose tissue inflammation and liver tissue oxidative stress of dams and their female offspring. Female BALB/c albino mice (60 days old) were randomized into three groups receiving a standard (CONT), hypercaloric (HD), or restricted (RD) diet during the pregnancy. After birth, female offspring weaned at 21 days were divided into two groups that received a standard or restricted diet (CONT/CONT, CONT/RD, RD/CONT, RD/RD, HD/CONT, and HD/RD) until 100 days old. Histological, oxidative parameters and inflammatory infiltrate of dams' and offspring's liver and adipose tissue were evaluated. HD dams presented non-alcoholic steatohepatitis (NASH) diagnosis and an increase in tumor necrosis factor-alpha (TNF-α) concentrations when compared to the RD and CONT dams, indicating a pro-inflammatory state. High concentrations of malondialdehyde (MDA) formation and catalase (CAT) activity in HD when compared to the CONT in the liver. SOD activity decreased in RD mice compared to CONT, and the SOD/CAT ratio was decreased in the RD and HD in comparison to the CONT. The maternal diet leads to an increase in SOD in RD/RD compared to HD/RD. RD-fed dams showed an increase in inflammatory infiltrates compared to CONT, evidencing changes caused by a restrictive diet. In the HD/CONT offspring, we verified an increase in inflammatory infiltrates in relation to the offspring fed a standard diet. In conclusion, HD, and RD, during pregnancy and lactation, altered the liver and adipose tissues of mothers. Furthermore, the maternal diet negatively impacts the offspring's adipose tissue but does not cause liver damage in these animals in adult life.

Calorie restriction mitigates metabolic, behavioral and neurochemical effects of cafeteria diet in aged male rats.

Besides metabolic dysfunctions, elderly individuals with obesity are at special risk of developing cognitive decline and psychiatric disturbances. Restricted calorie consumption could be an efficient strategy to improve metabolic function after obesity. However, its effects on anxiety-like behaviors in aged rats submitted to an obesogenic diet are unknown. For this purpose, 42 Wistar rats (18-months old) were divided into four groups: Control (CT), calorie restriction (CR), cafeteria diet (CAF), and CAF+CR (CAF/CR). CT, CR, and CAF groups received the diets for 8 weeks. CAF/CR group was submitted to the CAF menu for 7 weeks and then switched to a standard diet on a CR regimen, receiving 30% lower calories than consumed by the CT, for another 5 weeks. CAF's menu consisted of ultra-processed foods such as cookies, chocolate, sausage, and bologna. Body weight, visceral adiposity, and biochemical blood analysis were evaluated for obesity diagnosis. The profile of gut microbiota was investigated, along with circulating levels of LPS. Neurochemical parameters, such as neurotransmitter levels, were dosed. Anxiety-like behaviors were accessed using open field (OF) and elevated plus maze (EPM) tests. As expected, CR reduced weight gain and improved glucose homeostasis. Gut microbiome disturbance was found in CAF-fed animals accompanied by increased levels of LPS. However, CR after CAF mitigated several harmful responses. The obesogenic diet triggered anxiety-like manifestations in the OF and EPM tests that were not evidenced in the CAF/CR group. These findings indicate that CR can be a promising strategy for the neurological effects of obesity in aged rats.

Cannabidiol treatment improves metabolic profile and decreases hypothalamic inflammation caused by maternal obesity.

Introduction: The implications of maternal overnutrition on offspring metabolic and neuroimmune development are well-known. Increasing evidence now suggests that maternal obesity and poor dietary habits during pregnancy and lactation can increase the risk of central and peripheral metabolic dysregulation in the offspring, but the mechanisms are not sufficiently established. Furthermore, despite many studies addressing preventive measures targeted at the mother, very few propose practical approaches to treat the damages when they are already installed. Methods: Here we investigated the potential of cannabidiol (CBD) treatment to attenuate the effects of maternal obesity induced by a cafeteria diet on hypothalamic inflammation and the peripheral metabolic profile of the offspring in Wistar rats. Results: We have observed that maternal obesity induced a range of metabolic imbalances in the offspring in a sex-dependant manner, with higher deposition of visceral white adipose tissue, increased plasma fasting glucose and lipopolysaccharides (LPS) levels in both sexes, but the increase in serum cholesterol and triglycerides only occurred in females, while the increase in plasma insulin and the homeostatic model assessment index (HOMA-IR) was only observed in male offspring. We also found an overexpression of the pro-inflammatory cytokines tumor necrosis factor-alpha (TNFα), interleukin (IL) 6, and interleukin (IL) 1ß in the hypothalamus, a trademark of neuroinflammation. Interestingly, the expression of GFAP, a marker for astrogliosis, was reduced in the offspring of obese mothers, indicating an adaptive mechanism to in utero neuroinflammation. Treatment with 50 mg/kg CBD oil by oral gavage was able to reduce white adipose tissue and revert insulin resistance in males, reduce plasma triglycerides in females, and attenuate plasma LPS levels and overexpression of TNFα and IL6 in the hypothalamus of both sexes. Discussion: Together, these results indicate an intricate interplay between peripheral and central counterparts in both the pathogenicity of maternal obesity and the therapeutic effects of CBD. In this context, the impairment of internal hypothalamic circuitry caused by neuroinflammation runs in tandem with the disruptions of important metabolic processes, which can be attenuated by CBD treatment in both ends.

A high-fat diet changes placental morphology but does not change biochemical parameters, placental oxidative stress or cytokine levels.

INTRODUCTION: The placenta is an organ that forms the bridge between mother and fetus during pregnancy. Changes in the intrauterine environment directly impact the fetus' health, with maternal nutrition determining its development. This study analyzed the effects of different diets and probiotic supplementation during pregnancy on the biochemical parameters of maternal serum and placental morphology, oxidative stress, and cytokine levels in mice. METHODS: Female mice were fed standard (CONT), restrictive (RD), or high-fat (HFD) diets before and during pregnancy. During pregnancy, the CONT and HFD groups were divided into two groups that received the Lactobacillus rhamnosus LB1.5 three times per week (CONT + PROB and HFD + PROB). The RD, CONT, or HFD groups received vehicle control. Maternal serum biochemical parameters (glucose, cholesterol, and triglycerides) were evaluated. The morphology, redox profile (thiobarbituric acid reactive substances, sulfhydryls, catalase, and superoxide dismutase enzyme activity), and inflammatory cytokines (interleukins 1α, 1ß, IL-6, and tumor necrosis factor-alpha) were evaluated in the placenta. RESULTS: The serum biochemical parameters presented no differences between the groups. Regarding placental morphology, the HFD group showed an increased thickness of the labyrinth zone compared to the CONT + PROB group. However, no significant difference was found in the analysis of the placental redox profile and cytokine levels. DISCUSSION: RD and HFD, for 16 weeks before and during pregnancy, as well as probiotic supplementation during pregnancy, caused no change in serum biochemical parameters nor the gestational viability rate, placental redox state, and cytokine levels. However, HFD increased the thickness of the placental labyrinth zone.

Impact of cafeteria diet and n3 supplementation on the intestinal microbiota, fatty acids levels, neuroinflammatory markers and social memory in male rats.

OBJECTIVE: To assess the effects of omega-3 (n3) supplementation on intestinal microbiota, fatty acids profile, neuroinflammation, and social memory of cafeteria diet (CAF)-fed rats. METHODS: Male Wistar rats were fed with CAF for 20 weeks. Omega-3 (500 mg/kg/day) was supplemented between the 16th and 20th week. Colon morphology, intestinal microbiota composition, short-chain fatty acids (SCFA) and lipopolysaccharide (LPS) in the plasma, fatty acids profile, TLR-4 and claudin-5 expressions in the brain, and social memory were investigated. RESULTS: CAF reduced colon length, crypts' depth, and microbiota diversity, while n3 increased the Firmicutes/Bacteroidetes ratio. CAF increased SCFA plasma levels, but n3 reduced butyrate and isobutyrate in obese rats. LPS was increased in CAF-fed rats, and n3 decreased its levels. In the cerebral cortex, n3 increased caprylic, palmitic, stearic, tricosanoic, lignoceric, myristoleic, and linoleic acids. CAF increased palmitic acid and TLR-4 expression in the cerebral cortex while decreasing claudin-5 in the hippocampus. In the social memory test, CAF-fed animals showed greater social interaction with no effect of n3. CONCLUSIONS: The lack of n3 effect in some of the evaluated parameters may be due to the severity of the obesity caused by CAF. However, n3 reduced LPS levels, suggesting its ability to reverse endotoxemia.

Zinc Supplementation Partially Decreases the Harmful Effects of a Cafeteria Diet in Rats but Does Not Prevent Intestinal Dysbiosis.

Zinc (Zn) plays an important role in metabolic homeostasis and may modulate neurological impairment related to obesity. The present study aimed to evaluate the effect of Zn supplementation on the intestinal microbiota, fatty acid profile, and neurofunctional parameters in obese male Wistar rats. Rats were fed a cafeteria diet (CAF), composed of ultra-processed and highly caloric and palatable foods, for 20 weeks to induce obesity. From week 16, Zn supplementation was started (10 mg/kg/day). At the end of the experiment, we evaluated the colon morphology, composition of gut microbiota, intestinal fatty acids, integrity of the intestinal barrier and blood-brain barrier (BBB), and neuroplasticity markers in the cerebral cortex and hippocampus. Obese rats showed dysbiosis, morphological changes, short-chain fatty acid (SCFA) reduction, and increased saturated fatty acids in the colon. BBB may also be compromised in CAF-fed animals, as claudin-5 expression is reduced in the cerebral cortex. In addition, synaptophysin was decreased in the hippocampus, which may affect synaptic function. Our findings showed that Zn could not protect obese animals from intestinal dysbiosis. However, an increase in acetate levels was observed, which suggests a partial beneficial effect of Zn. Thus, Zn supplementation may not be sufficient to protect from obesity-related dysfunctions.

Neuroinflammatory responses following zinc or branched-chain amino acids supplementation in obese rats.

The excessive production of pro-inflammatory mediators, characteristic of obesity, leads to neuroinflammation. Zinc (Zn) and the branched-chain amino acids (BCAA) are supplements known for their immunomodulatory properties. Our goal was to evaluate if Zn or BCAA supplementation can affect long-term recognition memory and neuroinflammatory parameters of obese rats after a high-fat diet (HFD). Three-month-old Wistar rats were divided into six groups: Standard diet (SD) + vehicle; SD + Zn; SD + BCAA; High-fat diet (HFD) + vehicle; HFD + Zn; and HFD + BCAA. Diets were administrated for 19 weeks, Zn (1,2 mg/kg/day) or BCAA (750 mg/kg/day) supplementation was conducted in the last 4 weeks. Long-term recognition memory was evaluated by the novel object recognition test. IL-1ß immunoreactivity in the cortex and hippocampus, and IL-6 levels in the cortex tissue were assessed. Astrogliosis were evaluated through GFAP + cell count and morphological analysis (Sholl Method). Zn supplementation improved object recognition memory in HFD-fed rats, which was not observed following BCAA supplementation. The levels of IL-6 in the cerebral cortex were higher after HFD, which was not diminished after neither supplementation. Obesity also led to increased IL-1ß immunoreactivity in the cerebral cortex and hippocampus, which was reduced by Zn. BCAA supplementation also diminished IL-1ß immunoreactivity, but only in the hippocampus. We also showed that astrocyte reactivity caused by HFD is area-dependent, being the cerebral cortex more susceptible to the diet. Even though BCAA and Zn can affect IL-1ß immunoreactivity and astrocyte morphology, only Zn improved memory. Future studies are needed to clarify the pathways by which Zn improves cognition in obesity.

Caloric restriction in mice improves short-term recognition memory and modifies the neuroinflammatory response in the hippocampus of male adult offspring.

Restrictive diets (RD) can influence the inflammatory phenotype of dams and their offspring. Thus, this study aimed to evaluate the effects of caloric restriction on the neuroinflammatory profile in the hippocampus and the short-term recognition memory of male offspring from RD-fed dams. Mice dams received standard diet ad libitum (CONT) or restrictive diet (RD; 30% reduction of CONT consumption) during pregnancy and lactation. Male pups were weaned at 21 days and randomly divided into two groups that received CONT or RD; groups were named according to maternal/offspring diets: CONT/CONT, CONT/RD, RD/CONT, and RD/RD. At 90 days old, short-term memory was assessed by the object recognition test (ORT); the inflammatory state of the hippocampus was analyzed by gene expression of sirtuin-1 (Sirt1) and inflammasome Nlrp3; and by protein expression of toll-like receptor-4 (TLR-4) and zonula occludens-1 (ZO-1). Our results showed an improvement in short-term memory in RD-fed offspring. The expression of Sirt1 was higher in RD/CONT compared to CONT/CONT and decreased in RD/RD compared to CONT/RD. Nlrp3 gene expression showed an offspring effect, being decreased in RD-fed mice. TLR-4 expression was higher in RD/CONT compared to CONT/CONT, similarly to ZO-1 expression. However, ZO-1 also showed a maternal diet effect and increased expression in the offspring of RD dams. Our findings demonstrate that caloric restriction improved short-term recognition memory. However, a restrictive diet should be applied with caution; depending on the offspring's diet, it may not benefit the neuroinflammatory phenotype or cognition.

Mood Disorders Induced by Maternal Overnutrition: The Role of the Gut-Brain Axis on the Development of Depression and Anxiety.

Since the first evidence suggesting that maternal nutrition can impact the development of diseases in the offspring, much has been elucidated about its effects on the offspring's nervous system. Animal studies demonstrated that maternal obesity can predispose the offspring to greater chances of metabolic and neurodevelopmental diseases. However, the mechanisms underlying these responses are not well established. In recent years, the role of the gut-brain axis in the development of anxiety and depression in people with obesity has emerged. Studies investigating changes in the maternal microbiota during pregnancy and also in the offspring demonstrate that conditions such as maternal obesity can modulate the microbiota, leading to long-term outcomes in the offspring. Considering that maternal obesity has also been linked to the development of psychiatric conditions (anxiety and depression), the gut-brain axis is a promising target to be further explored in these neuropsychiatric contexts. In the present study, we review the relationship between maternal obesity and anxious and depressive features, exploring the gut-brain axis as a potential mechanism underlying this relationship.

Dietary interventions in mice affect oxidative stress and gene expression of the Prlr and Esr1 in the adipose tissue and hypothalamus of dams and their offspring.

Maternal diet is key to the progeny's health since it may impact on the offspring's adult life. In this study, mice dams received standard (CONT), restrictive (RD), or hypercaloric (HD) diets during mating, pregnancy, and lactation. Male offspring of each group of dams also received these diets: CONT, RD, HD. Aiming to evaluate the oxidative stress in the adipose tissue, reactive oxygen species (ROS) production, catalase (CAT), and superoxide dismutase (SOD) activities were analyzed in dams and offspring. In the adipose tissue and hypothalamus, gene expression of prolactin (Prlr) and estrogen alpha (Esr1) receptors was performed in dams and offspring. Protein expression of Stat5 was evaluated in the adipose tissue of the offspring from RD-fed dams. HD-fed dams increased triglycerides and leptin serum concentrations, and decreased SOD activity in the adipose tissue. In the offspring's adipose tissue, we observed a maternal diet effect caused by HD, with increased ROS production and SOD and CAT activities. Gene expression of Prlr and Esr1 in the offspring's adipose tissue was decreased due to maternal RD. Mice from HD-fed dams showed higher Stat5 expression compared to the offspring from CONT and RD dams in the adipose tissue. In the hypothalamus, we found decreased expression of Prlr in RD and HD dams, compared to CONT; and a maternal diet effect on Prlr and Esr1 gene expression in the offspring. In conclusion, we can affirm that maternal nutrition impacts the redox state and influences the gene expression of Prlr and Esr1, which are involved in energy metabolism, both peripherally and centrally in the adult life of the female offspring.

DHA/EPA supplementation decreases anxiety-like behaviour, but it does not ameliorate metabolic profile in obese male rats.

Obesity is a major public health problem that predisposes to several diseases and higher mortality in patients with COVID-19. Obesity also generates neuroinflammation, which predisposes to the development of neuropsychiatric diseases. Since there is a lack of effective treatments for obesity, the search for new strategies to reverse its consequences is urgent. In this perspective, the anti-inflammatory properties of omega-3 polyunsaturated fatty acids such as DHA/EPA might reduce the harmful effects of obesity. Here, we used the cafeteria diet (CAF) model to induce obesity in Wistar rats. Animals received ultra-processed food for 20 weeks, and DHA/EPA supplementation (500 mg/kg per d) was performed between the 16th and the 20th week. At the end of the experiment, it was evaluated: body weight, visceral fat deposition, plasma glucose, insulin and triglycerides, and it was also measured the levels of inflammatory cytokines TNF-α and IL-6 in plasma and liver, and TNF-α in the prefrontal cortex. The elevated plus maze test was performed to analyse anxiety-like behaviour. Our results demonstrated that DHA/EPA could not reverse weight and fat gain and did not modify plasma dosages. However, there was a decrease in IL-6 in the liver (DHA/EPA effect: P = 0.023) and TNF-α in the brain (CAF compared with CAF + DHA/EPA, P < 0.05). Also, there was a decrease in the anxiety index in CAF + DHA/EPA compared with the CAF group (P < 0.01). Thus, DHA/EPA supplementation is helpful to reverse the consequences of obesity in the brain.

Gene expression evaluation of antioxidant enzymes in patients with hepatocellular carcinoma: RT-qPCR and bioinformatic analyses.

Any condition leading to chronic liver disease is a potential oncogenic agent for hepatocellular carcinoma (HCC). Alterations in the expression of antioxidant enzymes could alter the redox balance. Our aim was to evaluate the expression of the genes GPX1, GPX4, SEP15, SELENOP, SOD1, SOD2, GSR, CAT, and NFE2L2 in patients with HCC. Differential gene expression analysis was performed using RNA-Seq data from the TCGA and GTEx databases, and RT-qPCR data from HCC patient samples. Bioinformatic analysis revealed significant differential expression in most genes. GPX4 expression was significantly increased (p=0.02), while SOD2 expression was significantly decreased (p=0.04) in experimental data. In TCGA samples, alpha-fetoprotein levels (mg/dL) were negatively correlated with the expression of SEP15 (p<0.001), SELENOP (p<0.001), SOD1 (p<0.001), SOD2 (p<0.001), CAT (p<0.001), and NFE2L2 (p=0.004). Alpha-fetoprotein levels were positively correlated with the expression of GPX4 (p=0.02) and SELENOP (p=0.01) in the experimental data. Low expression of GPX1 (p=0.006), GPX4 (p=0.01), SELENOP (p=0.006), SOD1 (p=0.007), CAT (p<0.001), and NFE2L2 (p<0.001), and higher levels of GSR, were associated with low overall survival at 12 months. These results suggest a significant role for these antioxidant enzymes in HCC pathogenesis and severity.

Zinc Supplementation Decreases Obesity-Related Neuroinflammation and Improves Metabolic Function and Memory in Rats.

OBJECTIVE: The purpose of this study was to evaluate the effects of zinc (Zn) supplementation on metabolic and neuroinflammatory parameters in cafeteria diet (CAF)-induced obesity in Wistar rats. METHODS: Animals were divided into four groups: control diet (CT); CT+Zn; CAF; CAF+Zn. The diet was administered for 20 weeks; Zn treatment (10 mg/kg/d) started at week 16 and it was conducted until the end of the diet protocol. Weight gain, visceral fat, and plasma levels of glucose, triglycerides, insulin, TNF-α, and IL-6, as well as homeostatic model assessment of insulin resistance, were assessed. Glial fibrillary acidic protein (GFAP) and ionized calcium binding adaptor molecule 1 (Iba-1) expression in the cerebral cortex and toll-like receptor 4 (TLR-4) in the cerebral cortex and hippocampus were evaluated. Memory was assessed by the novel object recognition test. RESULTS: CAF diet increased weight gain, visceral fat, and plasma glucose, triglyceride, and TNF-α levels. Zn reversed the hyperglycemia caused by CAF diet and reduced IL-6 levels. In the cerebral cortex, GFAP was similar between groups; Iba-1 was increased by CAF diet but reduced in the CAF+Zn group. Zn reduced CAF-dependent TLR-4 increase in the hippocampus but not in the cerebral cortex. CAF-fed animals showed impaired recognition memory, whereas Zn reversed it. CONCLUSIONS: These findings demonstrate that Zn partially reverted obesity-related metabolic dysfunction and reduced neuroinflammation and memory deficit caused by CAF diet.

Restriction and hyperlipidic diets during pregnancy, lactation and adult life modified the expression of dopaminergic system related genes both in female mice and their adult offspring.

The neurocircuitry underlying hunger, satiety, motivation to eat and food reward is complex, however a lot of mechanisms are still unknown. Two main cerebral areas are responsible for controlling feeding through hunger and food reward: the hypothalamus (HPT) and the ventral tegmental area (VTA), respectively. The dopaminergic system modulates both these areas and is essential to control food ingestion. Therefore, we aim to evaluate the effects of restrictive and hyperlipidic diets during pregnancy, lactation and during adult life of the offspring, on the expression of dopaminergic system genes in VTA and HPT of mice dams and their adult male offspring. We also measured diets' effect in locomotor activity in the open field (OF) test. Female mice were divided into control (CONT), restriction (RD) and hyperlipidic (HD) dietary groups, and mated with isogenic male mice. On the 9th postpartum day (PPD), dams were tested in the OF, and on the 22nd PPD cerebral areas were collected. After weaning, the offspring also were divided into one of three diet groups, independently of the diets provided to their dams. In the 80th PPD, the offspring was tested in the OF, and at 100th PPD, VTA and HPT were collected. Gene expression was analyzed by quantitative reverse transcription real-time polymerase chain reaction. The correlation between gene expression and locomotor activity was also assessed. In dams' VTA, both diets upregulated the expression of Th, Slc6a3/Dat1, Drd1 and Drd2 genes. In opposition, in the offspring the maternal diet was associated with a reduction in Th and Ddc gene expression. In the HPT, mice dams that received restriction or hyperlipidic diets had increased Th mRNA levels, but reduced the expression of Drd4 gene. The offspring diet had no effect on the expression of the studied genes in their adult lives. Both diets increased mice dam's locomotion in the OF, however none of them altered the offspring locomotor activity. We detected a positive correlation between the duration of total locomotion in the OF and Slc6a3/Dat1 gene expression in VTA of mice dams. In the HPT, a negative correlation of locomotion and Drd4 mRNA levels, and a positive correlation with Th gene expression was observed. Our results show that restriction and hyperlipidic diets alter mice dams' locomotor activity in the OF and modify the expression of dopaminergic system genes in VTA and HPT of mice dams and in VTA of the offspring.

Neurotrophic factors in the posterodorsal medial amygdala of male and cycling female rats.

The posterodorsal medial amygdala (MePD) has a high concentration of receptors for gonadal hormones, is a sexually dimorphic region and dynamically controls the reproductive behavior of both males and females. Neurotrophic factors can promote dendritic spine remodeling and change synaptic input strength in a region-specific manner. Here, we analyzed the gene and protein expression of brain-derived neurotrophic factor (BDNF), insulin-like growth factor-I (IGF-1), polysialylated neural cell adhesion molecule (PSA-NCAM) and Ephrin-A4 in the MePD of adult males and females in diestrus, proestrus and estrus using real-time qPCR and fluorescent immunohistochemistry. The first approach showed their amplification except for Igf1 and the latter revealed that BDNF, IGF-1, PSA-NCAM and Ephrin-A4 are expressed in the MePD of the adult rats. Protein expression of these neurotrophic factors showed no differences between groups. However, proestrus females displayed a higher number of labelled puncta than males for BDNF expression and diestrus females for IGF-1 expression. In conjunction, results indicate that IGF-1 might be released rather than synthetized in the MePD, and the expression of specific neurotrophic factors varies specifically during proestrus. The dynamic modulation of BDNF and IGF-1 during this cyclic phase is coincident with synaptic changes and spine density remodeling in the MePD, the disinhibition of gonadotrophin secretion for ovulation and the display of sexual behavior.

Food Selection of Cafeteria Diet Affects Memory Dysfunction Related to Obesity.

Cafeteria diet (CAF) mimics human Western diet and has been used in animal models to study obesity. The purpose of this study is to demonstrate that our CAF model induces metabolic disorder related to obesity and affects recognition memory in Wistar rats. We also compared the intake of two different soft drinks, as part of the CAF, on recognition memory. Our results demonstrate that CAF-fed rats increased weight gain and visceral adiposity, and exhibited hyperglycemia, hypertriglyceridemia, high leptin and low insulin plasma levels. Moreover, CAF animals showed higher lipid peroxidation in the liver and developed non-alcoholic fatty liver disease. Surprisingly, the group fed with cola-based soft drinks presented an improvement in recognition memory, whereas animals fed with orange-based soft drinks showed worse performance in this task. Our data indicates that CAF induces obesity and affects recognition memory, but the composition of the diet interfere when the neurological function is evaluated.

Altered expression of COX-2 and TNF-alfa in patients with hepatocellular carcinoma

Background and aim: hepatocellular carcinoma is a type of cancer related with inflammation, as 90% of cases develop in a chronic inflammation condition. Excess inflammation can affect tissue homeostasis. Cytokines and inflammatory mediators are immunological components that can influence the functioning of cells and tissues. In addition, the estrogen receptor appears to play an important role in hepatocarcinogenesis. The aim of the study was to evaluate the expression of inflammatory markers and ER in patients with hepatocellular carcinoma. Methods: data from 143 patients of ISCMPA were analyzed. Immunohistochemistry was performed of cyclooxygenase-2 enzyme (COX-2), nuclear factor kappa B (NF-κB), tumor necrosis factor alpha (TNF-alfa) and ER in paraffin-embedded hepatic tissue. The percentage of the stained area, intensity of staining and of the number of ER positive nuclei were evaluated using the ImageJ 1.50 software. Results and conclusion: there was a significant difference between the groups in terms of the percentage of marked area (p = 0.040) for COX-2 and the intensity of staining of TNF-alfa (p = 0.030). No significant differences were observed in any of other parameters evaluated. In conclusion, COX-2 and TNF-alfa are possible markers that should be further studied to determine their immunohistochemical profile and role in HCC development

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Altered expression of COX-2 and TNF-α in patients with hepatocellular carcinoma.

BACKGROUND AND AIM: hepatocellular carcinoma is a type of cancer related with inflammation, as 90% of cases develop in a chronic inflammation condition. Excess inflammation can affect tissue homeostasis. Cytokines and inflammatory mediators are immunological components that can influence the functioning of cells and tissues. In addition, the estrogen receptor appears to play an important role in hepatocarcinogenesis. The aim of the study was to evaluate the expression of inflammatory markers and ER in patients with hepatocellular carcinoma. METHODS: data from 143 patients of ISCMPA were analyzed. Immunohistochemistry was performed of cyclooxygenase-2 enzyme (COX-2), nuclear factor kappa B (NF-κB), tumor necrosis factor alpha (TNF-α) and ER in paraffin-embedded hepatic tissue. The percentage of the stained area, intensity of staining and of the number of ER positive nuclei were evaluated using the ImageJ 1.50 software. RESULTS AND CONCLUSION: there was a significant difference between the groups in terms of the percentage of marked area (p = 0.040) for COX-2 and the intensity of staining of TNF-α (p = 0.030). No significant differences were observed in any of other parameters evaluated. In conclusion, COX-2 and TNF-α are possible markers that should be further studied to determine their immunohistochemical profile and role in HCC development.