Amanda Alves Marcelino da Silva

Perinatal undernutrition stimulates seeking food reward.

Experiments in animals have revealed that perinatal nutritional restriction, which manifests in adulthood, increases food intake and preference for palatable foods. Considering this, we aimed to evaluate the effects of perinatal malnutrition on hedonic control of feeding behavior. In this study, we divided Wistar rats into two groups according to the diet provided to their mothers during pregnancy and lactation: the control group (diet with 17% casein) and low‐protein group (diet with 8% casein). We assessed the animals’ motivational behavior in adulthood by giving them a stimulus of food reward. We also assessed their neuronal activation triggered by the stimulus of palatable food using FOS protein labeling of neurons activated in the caudate putamen, paraventricular, dorsomedial, ventromedial, and lateral hypothalamic nuclei and amygdala. Evaluation of body weight in malnourished animals showed reduction from the 6th day of life until adulthood. Analysis of feeding behavior revealed that these animals were more motivated by food reward, but they had delays during learning of the task. This finding correlated with the number of c‐FOS‐immunoreactive neurons, which indicated that malnourished animals had an increase in the number of neurons activated in response to the palatable diet, especially in the amygdala and caudate putamen. The study therefore confirmed our hypothesis that early nutritional insults promote changes in encephalic control mechanisms, especially those related to food intake and search for reward.

Perinatal malnutrition stimulates motivation through reward and enhances drd1a receptor expression in the ventral striatum of adult mice

AIM The aim of this study was to analyze the effects of protein perinatal malnutrition on the function of dopamine DRD1 and DRD2 receptors in regards to motivation and food consumption in adult mice. The study also analyzed the effect of protein perinatal malnutrition on the gene expression of these receptors in the ventral striatum. METHODS Wistar lineage mice were divided into two groups according to maternal diet: control (17% casein), n=30 and low protein (8% casein), n=30. Between 30 and 120days of life, the following factors were measured: body weight; the effect of dopamine D1 and D2 agonists on the ingestion of palatable food; the motivational aspect under the action of the D1 (SKF 38393) and D2 Quinpirole dopaminergic agonists; and the gene expression of DRD1 and DRD2 receptors in the ventral striatum. RESULTS The body weights of the malnourished animals remained significantly lower than those of the control group from 30 to 120days of life. Malnourished animals ingested a greater quantity of palatable food. There was a decrease in palatable diet consumption in both the control and malnourished groups after the application of D1 and D2 agonists; however, the anorexic effect of the D1 agonist was understated in malnourished animals. Perinatal malnutrition increases the motivational behavior of the animal when food reward is used. There was an increase in gene expression of the DRD1a receptor in the ventral striatum of malnourished animals, and there were no significant changes concerning the DRD2 receptor. CONCLUSIONS Perinatal protein malnutrition stimulates hedonic control of eating behavior by promoting increased intake of palatable foods, possibly due to increased expression of dopamine receptor DRD1a in the ventral striatum.

Effects of perinatal protein malnutrition and fenfluramine action on food intake and neuronal activation in the hypothalamus and raphe nuclei of neonate rats.

In neonatal rats, hunger and satiety responses occur particularly via dehydration and gastric distention, respectively. The control of food intake in newborns is yet to be fully consolidated, particularly with respect to the participation of the hypothalamic nuclei and their relationship with the serotonergic pathway. Moreover, it is unclear how the environmental stressors in early life, like undernutrition, interfere in these events. Therefore, this study examined the serotonin-systems impact on food intake in rat neonates at postnatal day (P) 10 and P18 and the manner in which protein undernutrition during pregnancy and lactation interferes in this behavior. To accomplish this, Wistar rats were used, nutritionally manipulated by a diet having two protein levels, (8% and 17%) during pregnancy and lactation, to form the Control (n=10) and Low protein groups (n=10). At 10 and 18 postnatal days pups received an acute dose of fenfluramine (3mg/kg) or saline (0.9% NaCl) and subjected to milk consumption testing and then perfused to obtain the brains for the analysis of cell activation of the immunoreactive c-Fos in the hypothalamic and raphe nuclei. At 10days a reduction in weight gain was observed in both groups. On comparison of the neuronal activation for the paraventricular nucleus, an increased activation in response to fenfluramine was observed. At 18days, the weight gain percentage differed between the groups according to the nutritional manipulation, in which the control animals had no significant change while the undernourished presented increased weight gain with the use of fenfluramine. The marking of c-Fos in response to fenfluramine in the hypothalamic and raphe nuclei revealed, an especially lower activation of the PVN, MnR and DR compared intra-group. However when evaluating the effect of undernutrition, marking activation was observed to increase in all the nuclei analyzed, in the hypothalamus and raphe. Data from this study indicate that the action of serotonin via food intake in the neonates may have been delayed by early protein undernutrition.

Flavonoids as Therapeutic Agents in Alzheimer’s and Parkinson’s Diseases: A Systematic Review of Preclinical Evidences

Alzheimers and Parkinsons diseases are considered the most common neurodegenerative disorders, representing a major focus of neuroscience research to understanding the cellular alterations and pathophysiological mechanisms involved. Several natural products, including flavonoids, are considered able to cross the blood-brain barrier and are known for their central nervous system-related activity. Therefore, studies are being conducted with these chemical constituents to analyze their activities in slowing down the progression of neurodegenerative diseases. The present systematic review summarizes the pharmacological effects of flavonoids in animal models for Alzheimers and Parkinsons diseases. A PRISMA model for systematic review was utilized for this search. The research was conducted in the following databases: PubMed, Web of Science, BIREME, and Science Direct. Based on the inclusion criteria, 31 articles were selected and discussed in this review. The studies listed revealed that the main targets of action for Alzheimers disease therapy were reduction of reactive oxygen species and amyloid beta-protein production, while for Parkinsons disease reduction of the cellular oxidative potential and the activation of mechanisms of neuronal death. Results showed that a variety of flavonoids is being studied and can be promising for the development of new drugs to treat neurodegenerative diseases. Moreover, it was possible to verify that there is a lack of translational research and clinical evidence of these promising compounds.

Nuclear organization and morphology of cholinergic neurons in the brain of the rock cavy (Kerodon rupestris) (Wied, 1820)

The aim of this study was to conduct cytoarchitectonic studies and choline acetyltransferase (ChAT) immunohistochemical analysis to delimit the cholinergic groups in the encephalon of the rock cavy (Kerodon rupestris), a crepuscular Caviidae rodent native to the Brazilian Northeast. Three young adult animals were anesthetized and transcardially perfused. The encephala were cut in the coronal plane using a cryostat. We obtained 6 series of 30-μm-thick sections. The sections from one series were subjected to Nissl staining. Those from another series were subjected to immunohistochemistry for the enzyme ChAT, which is used in acetylcholine synthesis, to visualize the different cholinergic neural centers of the rock cavy. The slides were analyzed using a light microscope and the results were documented by description and digital photomicrographs. ChAT-immunoreactive neurons were identified in the telencephalon (nucleus accumbens, caudate-putamen, globus pallidus, entopeduncular nucleus and ventral globus pallidus, olfactory tubercle and islands of Calleja, diagonal band of Broca nucleus, nucleus basalis, and medial septal nucleus), diencephalon (ventrolateral preoptic, hypothalamic ventrolateral, and medial habenular nuclei), and brainstem (parabigeminal, laterodorsal tegmental, and pedunculopontine tegmental nuclei). These findings are discussed through both a functional and phylogenetic perspective.

Synthesis and evaluation of arylamidine derivatives for new antimicrobial and cytotoxic activities

A series of arylamidines 3a-j was designed, synthesized and investigated for antimicrobial activity. Structures of the compounds were confirmed by IR, 1H-NMR and 13C-NMR and a 2D spectroscopic study was performed. A preliminary screening of the antimicrobial tests clearly showed that three out of ten arylamidines, viz, 3f, 3g and 3i, were effective against all the gram-negative bacteria: Klebsiella pneumoniae, Pseudomonas aeruginosa and Salmonella enteric; and against the yeast, candida albicans. Further, the Minimum Inhibitory Concentrations (MIC) against the bacteria and yeast were determined. All compounds 3a-d, 3f, 3g, 3i and 3j were also investigated for their low cytotoxic effects on tested cell lines. Compounds 3d and 3f were the most effective derivatives against HL-60 and HEp-2 cells, respectively, with IC50 value (2µg/mL), and low normal cells toxicity.

Early exposure of dams to a westernized diet has long-term consequences on food intake and physiometabolic homeostasis of the rat offspring

Abstract This study evaluated the long-term effects of a westernized diet during pregnancy and lactation. Female Wistar rats (n = 12) were divided into two groups according to their food intake, namely, control (C) or westernized (W) diet, throughout pregnancy/lactation. On the 21st day, the male pups were weaned on a standard diet as follows: Control diet (CC) (n = 8) and westernized diet in perinatal life followed by control diet post weaning (WC) (n = 8). The levels of fasting (12 h) serum glucose, triglycerides (TG), and total cholesterol and fraction in the pups were determined. During weaning, the WC group showed 14% greater body weight (p < 0.001). In the adulthood, the offspring from dams fed on westernized diet showed hyperphagia, hyperinsulinism, hypertriglyceridemia, higher fat visceral weight, higher very-low-density-lipoprotein cholesterol level, decreased high-density-lipoprotein cholesterol level, and altered glucose tolerance test. In conclusion, maternal western-style diet in early life altered long-term food intake, visceral fat pad, insulin, glucose and lipid serum, and increased risk of metabolic disorders.