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 Student's 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.

Maternal intake of flaxseed-based diet (Linum usitatissimum) on hippocampus fatty acid profile: implications for growth, locomotor activity and spatial memory.

OBJECTIVE: To investigate flaxseed as a partial source of protein and an exclusive source of lipids and fibers in the development of the central nervous system by analyzing hippocampal fatty acid composition and cognitive and locomotor functions. METHODS: Experimental diets were given to dams during preconception, pregnancy, and lactation and to their pups after weaning. Female Wistar rats were separated into three groups according to experimental diet: a control group (CG) and a flaxseed group (FG), fed ad libitum diets, and a modified control group (MCG), pair-fed with the FG. After weaning, the pups received their mothers' diets. After 30 d, eight males from each group were tested in a Morris water maze to assess learning, memory, and motor function. RESULTS: The offspring of FG dams showed a lower body mass than CG dams, probably due to non-nutritional factors and an imbalance between ω-3 and ω-6 fatty acids of the seed, and displayed a higher concentration of α-linolenic acid, possibly suggesting inhibition of arachidonic acid synthesis. The content of docosahexaenoic acid in the hippocampus was higher in the FG followed by the MCG compared with the CG. Hippocampal docosahexaenoic acid content correlated with better spatial memory performance in the FG, whereas arachidonic acid content correlated with longer time in solving the task. CONCLUSION: Flaxseed during perinatal and postweaning periods improves spatial memory to the detriment of growth. These findings indicate that there must be caution in encouraging the maternal intake of flaxseed during pregnancy and lactation.

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.

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.