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.

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.

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.