Amanda Santos de Souza

Effects of maternal malnutrition and postnatal nutritional rehabilitation on brain fatty acids, learning, and memory

Undernutrition still affects mothers and children in developing countries and thus remains the major focus of nutritional intervention efforts. Neuronal development, which classically includes neurogenesis, migration, maturation, and synapse refinement, begins in utero and continues into the early postnatal period. These processes are not only genetically regulated but also clearly susceptible to environmental manipulation. Dietary deprivation during early life is known to have adverse effects on brain anatomy, physiology, and biochemistry, and may even lead to permanent brain damage. Although all nutrients are important for the structural development of the central nervous system, lipids such as long-chain polyunsaturated fatty acids, especially docosahexaenoic acid (22:6 n-3) and arachidonic acid (20:4 n-6), are important for normal brain development. The purpose of this literature review is to examine how early undernutrition involving a deficiency in long-chain polyunsaturated fatty acids can affect brain development and function and produce deficits in spatial cognitive learning ability.

Brain fatty acid profiles and spatial learning in malnourished rats: effects of nutritional intervention

Abstract The aim of the present study was to determine the effects of malnutrition and nutritional rehabilitation on learning and memory performance and brain fatty acid composition. Pregnant and lactating Wistar rats were either fed ad libitum on a commercial laboratory chow or a multideficient diet from north-eastern Brazil (regional basic diet; RBD). After weaning, RBD offspring either continued on the multideficient diet (malnourished group) or switched to a control diet (rehabilitated group), until day 70. There was no difference in the passive avoidance test among the experimental groups, but malnourished rats showed important deficits in performance of the Morris water maze which were improved in the rehabilitated group. The hippocampus and cerebellum of the malnourished rats showed important changes in fatty acid profile obtained by gas-liquid chromatography, but the rehabilitated group had decreased n-3 polyunsaturated fatty acids and an increase in the proportion of arachidonic acid. The data suggest that nutritional rehabilitation results in partial restoration of fatty acid profiles and cognitive performance.

Trypanosoma cruzi-induced depressive-like behavior is independent of meningoencephalitis but responsive to parasiticide and TNF-targeted therapeutic interventions

Inflammatory cytokines and microbe-borne immunostimulators have emerged as triggers of depressive behavior. Behavioral alterations affect patients chronically infected by the parasite Trypanosoma cruzi. We have previously shown that C3H/He mice present acute phase-restricted meningoencephalitis with persistent central nervous system (CNS) parasitism, whereas C57BL/6 mice are resistant to T. cruzi-induced CNS inflammation. In the present study, we investigated whether depression is a long-term consequence of acute CNS inflammation and a contribution of the parasite strain that infects the host. C3H/He and C57BL/6 mice were infected with the Colombian (type I) and Y (type II) T. cruzi strains. Forced-swim and tail-suspension tests were used to assess depressive-like behavior. Independent of the mouse lineage, the Colombian-infected mice showed significant increases in immobility times during the acute and chronic phases of infection. Therefore, T. cruzi-induced depression is independent of active or prior CNS inflammation. Furthermore, chronic depressive-like behavior was triggered only by the type I Colombian T. cruzi strain. Acute and chronic T. cruzi infection increased indoleamine 2,3-dioxygenase (IDO) expression in the CNS. Treatment with the selective serotonin reuptake inhibitor (SSRI) fluoxetine abrogated the T. cruzi-induced depressive-like behavior. Moreover, treatment with the parasiticide drug benznidazole abrogated depression. Chronic T. cruzi infection of C57BL/6 mice increased tumor necrosis factor (TNF) expression systemically but not in the CNS. Importantly, TNF modulators (anti-TNF and pentoxifylline) reduced immobility. Therefore, direct or indirect parasite-induced immune dysregulation may contribute to chronic depressive disorder in T. cruzi infection, which opens a new therapeutic pathway to be explored.

Effects of a normolipidic diet containing trans fatty acids during perinatal period on the growth, hippocampus fatty acid profile, and memory of young rats according to sex

OBJECTIVE To investigate whether dietary trans fatty acids (TFAs) are incorporated in the hippocampus and its effects on the growth and aversive and spatial memories of young rats. METHODS Wistar rat offspring whose mothers were fed with normolipidic diets containing soybean oil (soy group) or hydrogenated vegetable oil (trans group) during gestation and lactation were used. Male and female pups received the same diets as their mothers until the end of behavioral testing. The composition of fatty acids in the total lipids of the diets and hippocampus was quantified by gas chromatography. The results were evaluated by Students t test or analysis of variance followed by the Bonferroni correction. RESULTS The trans male and female body weights were higher during lactation and after weaning, with trans males having the lower body weight of the two. There was incorporation of 0.11% and 0.17% of TFAs in the hippocampi of male and female rats, respectively. During passive avoidance test, there was no significant difference. In the water maze test, there was no significant difference between male groups in the training and retention phases, except on day 4, when there was a significant decrease in latency in trans males. Trans females were worse on day 2 only and showed an improvement in spatial memory during the probe trial. CONCLUSION The TFAs were incorporated in small amounts in the hippocampus and did not affect aversive memory. However, spatial memory was modified in young rats fed with a diet rich in TFAs. These findings suggested that, in addition to the TFA content of the diet provided, it is important to consider the provision of essential fatty acids and the ω-6/ω-3 ratio.

Interesterified fat or palm oil as substitutes for partially hydrogenated fat in maternal diet can predispose obesity in adult male offspring

BACKGROUND & AIMS Palm oil (PO) and interesterified fat (IF) have been used to replace partially hydrogenated fat (PHF), which is rich in trans isomers, in processed foods. The purpose of this study was to investigate whether normolipidic diets containing PHF, IF, or PO consumed during pregnancy and lactation affect total body adiposity and adipose tissue morphology of adult offspring mice. METHODS Four groups of female C57BL/6 mice were fed, during pregnancy and lactation, a control diet (control group, CG), a PHF diet (trans group, TG), a PO diet (PG group), or an IF diet (IG group). After weaning (at 21 days), male pups received the control diet for 70 days. Food intake and body weight were monitored in all groups throughout the experimental period. At 3 months of age, mice were sacrificed and the inguinal (IWAT), epididymal (EWAT), retroperitoneal (RPWAT), and mesenteric (MWAT) adipose fat pads were removed and weighed. Adiposity was quantified by micro computed tomography (micro-CT), and adipocyte areas and cell number were analyzed by histology. RESULTS PG and IG offspring gained more weight than CG and TG groups (p < 0.01) during the first 10 weeks after weaning, resulting in higher final body weights (p < 0.05). IG mice and PG mice had respectively heavier EWAT and IWAT than TG and CG mice. Micro-CT scanning revealed that the total volumes of internal, external, and total fat depots were greater in IG animals, as compared to the other groups. Larger adipocyte areas were observed in EWAT and IWAT in IG and TG, respectively, in comparison to CG and PG mice. PG mice showed increased adipocyte numbers in IWAT. CONCLUSIONS Maternal intake of IF and/or PO during pregnancy and lactation predisposes the offspring to the development of obesity in adult life in mice.

Effects of protein restriction during gestation and lactation on cell proliferation in the hippocampus and subventricular zone: Functional implications. Protein restriction alters hippocampal/SVZ cell proliferation

There is no consensus about the effects of protein restriction on neurogenesis and behavior. Here, for the first time, we evaluated the effects of protein restriction during gestation and lactation, on the two major neurogenic regions of the adult brain, the subgranular zone (SGZ) of the hippocampal dentate gyrus and the subventricular zone (SVZ), simultaneously. We also assessed different types of behavior relevant to each region. After mating, pregnant Wistar rats were divided into a control group (CG) that received a normal diet (20% protein); and a protein-restriction group (PRG) that received a low-protein diet (8% protein). After birth, the same diets were provided to the mother and pups until weaning, when some rats were analyzed and others received a normal-protein diet until adulthood. Different sets of rats were used for cellular and behavioral studies in juvenile or adult age. Brains were processed for immunohistochemistry anti-BrdU, anti-Ki67, or anti-pHisH3. Juvenile and adult rats from distinct litters also underwent several behavioral tests. Our data show that early protein restriction results in a reduction of hippocampal progenitors and deficits in object recognition during adult life. Moreover, longer periods of immobility in the tail suspension and in the forced swimming tests revealed that PRG rats show a depressive behavior at 21 days of age (P21) and in adulthood. Furthermore, we suggest that despite the reduced number/proliferation of neural stem cells (B and/or E cells) in SVZ there is a compensatory mechanism in which the progenitors (types C and A cells) proliferate in a higher rate, without affecting olfactory ability in adulthood.

Paralytic activity of lysophosphatidylcholine from saliva of the waterbug Belostoma anurum

SUMMARY Lysophosphatidylcholine (LPC) is a major bioactive lipid that is enzymatically generated by phospholipase A2 (PLA2). Previously, we showed that LPC is present in the saliva of the blood-sucking hemipteran Rhodnius prolixus and modulates cell-signaling pathways involved in vascular biology, which aids blood feeding. Here, we show that the saliva of the predator insect Belostoma anurum contains a large number of lipids with LPC accounting for 25% of the total phospholipids. A PLA2 enzyme likely to be involved in LPC generation was characterized. The activity of this enzyme is 5-fold higher in Belostoma saliva than in other studied hemipterans, suggesting a close association with the predator feeding habits of this insect. Belostoma employs extra-oral digestion, which allows for ingestion of larger prey than itself, including small vertebrates such as amphibians and fish. Therefore, prey immobilization during digestion is essential, and we show here that Belostoma saliva and B. anurum saliva purified LPC have paralytic activity in zebrafish. This is the first evidence that lysophospholipids might play an important role in prey immobilization, in addition to contributing to blood feeding, and might have been an evolutionary acquisition that occurred long before the appearance of hematophagy in this animal group.

Interesterified fat or palm oil as substitutes for partially hydrogenated fat during the perinatal period produces changes in the brain fatty acids profile and increases leukocyte-endothelial interactions in the cerebral microcirculation from the male offspring in adult life

We investigated whether maternal intake of normolipidic diets with distinct fatty acid (FA) compositions alters the lipidic profile and influences the inflammatory status of the adult offsprings׳ brains. C57BL/6 female mice during pregnancy and lactation received diets containing either soybean oil (CG), partially hydrogenated vegetable fat rich in trans-fatty acids (TG), palm oil (PG), or interesterified fat (IG). After weaning, male offspring from all groups received control diet. The FA profile was measured in the offspring׳s brains at post-natal days 21 and 90. Brain functional capillary density as well as leukocyte-endothelial interactions in the cerebral post-capillary venules was assessed by intravital fluorescence microscopy at post-natal day 90. Inflammation signaling was evaluated through toll-like receptor 4 (TLR4) content in brain of the adult offspring. In the 21-day old offspring, the brains of the TG showed higher levels of trans FA and reduced levels of linoleic acid (LA) and total n-6 polyunsaturated fatty acids (PUFA). At post-natal day 90, TG and IG groups showed reduced levels of eicosapentaenoic acid (EPA) and total n-3 PUFA tended to be lower compared to CG. The offspring׳s brains exhibited an altered microcirculation with increased leukocyte rolling in groups TG, PG and IG and in TG group increased leukocyte adhesion. The TLR4 content of TG, IG and PG groups only tended to increase (23%; 20% and 35%, respectively). Maternal consumption of trans FA, palm oil or interesterified fat during pregnancy and lactation can trigger the initial steps of inflammatory pathways in the brain of offspring in adulthood.

Influência da desnutrição promovida pela dieta básica regional sobre o perfil de ácidos graxos do leite materno, o crescimento e o desenvolvimento de ratos jovens

OBJETIVO: Avaliar os efeitos do consumo da Dieta Basica Regional e da reabilitacao nutricional, durante os periodos criticos de crescimento e desenvolvimento de ratos, sobre a evolucao da sua massa corporal e tecidual, bem como o consumo alimentar de maes durante a gestacao e lactacao e de seus filhotes, machos e femeas, ate 70 dias de vida. Adicionalmente, verificou-se o percentual dos acidos graxos nas dietas experimentais e no leite materno. METODOS: Foram utilizados ratos Wistar, de ambos os sexos. Apos a constatacao da prenhez, as ratas foram divididas em tres grupos. 1) Grupo controle, animais alimentados com racao comercial durante o periodo de gestacao e lactacao (maes e filhotes) e, apos o desmame, os filhotes ate 70 dias de vida; 2) Grupo desnutrido, animais alimentados com racao Dieta Basica Regional durante o mesmo periodo descrito para o grupo controle e 3) Grupo recuperado, animais alimentados com racao Dieta Basica Regional durante o periodo de gestacao e lactacao e os filhotes, apos o desmame, alimentados com racao comercial ate 70 dias de vida. Os animais foram monitorados diariamente, aferindo-se a massa corporal e o consumo alimentar. Os filhotes com 70 dias de vida foram sacrificados por decapitacao e o cerebro, o coracao, o figado e os rins foram retirados e pesados. Os animais receberam agua e racao ad libitum e foram mantidos em bioterio com temperatura e luminosidade controladas. Os testes estatisticos utilizados foram o teste t de Student, a Analise de Variância e o pos-teste de Bonferroni. RESULTADOS: Foram encontradas alteracoes importantes no percentual de acidos graxos essenciais na Dieta Basica Regional, assim como no leite materno das maes desnutridas. O ganho de peso das maes desnutridas e de seus respectivos filhotes, tanto machos quanto femeas, foi menor que o de animais controle desde a lactacao ate o final do experimento. As femeas recuperadas apresentaram valores de massa corporal estatisticamente semelhantes aos do grupo controle, o que nao foi observado nos filhotes machos do grupo recuperado. CONCLUSAO: O comprometimento da massa corporal materna durante a lactacao e o deficit na taxa de crescimento dos filhotes, machos e femeas, se deveram a ingestao da Dieta Basica Regional multideficiente. A diminuicao dos teores de acidos graxos especificos do leite materno poderia, ainda que nao completamente, justificar o deficit de crescimento observado.