Early and post-weaning malnutrition impairs alpha-MSH expression in the hypothalamus: a possible link to long-term overweight

Abstract

The present study explored the effects of early and post-weaning malnutrition and nutritional rehabilitation on orexigenic (orexin (ORX) and neuropeptide Y (NPY)) and anorexigenic peptides (alpha-melanocyte stimulating hormone (alpha-MSH)) expressed in hypothalamic nuclei. Male Wistar rats were malnourished during gestation–lactation (MGL) or from weaning to post-natal day 55 (MPW; P55). Two groups of rats were rehabilitated with a balanced diet until P90 (MGL-R and MPW-R, respectively). After a glucose tolerance test (GTT) brains were processed for immunohistochemistry. Malnourished groups were hyperglycemic after GTT. ORX expression did not display any difference. Only MGL rats showed increased NPY immunoreactivity in ARC and PVN nuclei, and both malnourished groups showed low alpha-MSH expression in the PVN and DMH, as compared with their controls. After nutritional rehabilitation rats showed normal GTT, increased rate of body and adipose tissue weights and high proportion of food ingestion. Both rehabilitated groups maintained low alpha-MSH expression in the PVN, indicating a deleterious long-lasting effect.     

Altered Fos immunoreactivity in the hypothalamus after glucose administration in pre- and post-weaning malnourished rats

Abstract

The present study explored the effects of malnutrition and nutritional rehabilitation on the response to glucose in hypothalamic nuclei involved in metabolic homeostasis. Male Wistar rats were malnourished during gestation–lactation (MGL) or at weaning to 55 days (MPW). Two groups of rats were rehabilitated with a balanced diet until 90 days (MGL-R and MPW-R, respectively). After a glucose tolerance test (GTT), brains were processed for Fos immunoreactivity (Fos-IR). Both malnourished groups displayed hyperglycemia after GTT. MGL exhibited an increased number of Fos-IR neurons in the ventromedial hypothalamic nucleus (VMH), while MPW showed increased Fos-IR in the arcuate nucleus (ARC) and VMH and a decrease in the paraventricular nucleus (PVN), as compared with their controls. Nutritional rehabilitation normalized values of glucose after GTT in both groups, while low number of Fos-IR neurons remained in the ARC, PVN and VMH of MPW-R rats, indicating a deleterious, long-lasting effect after post-weaning malnutrition.     

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.     

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.     

Hypothalamic nuclei nitric oxide synthase expression in rats malnourished during early lactation period

In humans and other animals, it has been shown that protein malnutrition during the prenatal period leads to permanent changes, which in adulthood may cause chronic diseases. Molecules involved in the control of energy metabolism could be targets to alterations caused by nutritional status. Some hypothalamic nuclei as the paraventricular (PVN), ventro-medial and arcuate are related to energy metabolism regulation. Orexigenic and anorexigenic molecules are involved in this regulation. Some studies have showed that these nuclei present nitric oxide synthase (NOS) and that it is increased in obese rats. Recently it had been shown that rats malnourished during the lactation period presented metabolic alterations that persist in adulthood. The aim of this work was to study the expression of NOS in hypothalamic nuclei of rats submitted to malnutrition during the early lactation period. Rats from post-natal day (P10) to P90 were used. Control dams were fed with regular chow pellets and diet dams were fed with protein-free chow pellets during the first 10 days of lactation. NADPH-diaphorase or immunostaining techniques were used to access NOS expression in hypothalamic nuclei. Our results show a delay in NOS expression in the PVN and VMH of malnourished rats. It may affect the development of the hypothalamic circuitry, leading to a metabolic imprinting.     

The rehabilitation of malnourished rats with different sources of dietary lipids

Effects of different sources of dietary lipids with varying levels of essential fatty acids (EFA) were investigated as the only variables in the rehabilitation of rats previously malnourished by feeding a restricted amount of a low protein, low fat diet for 6 weeks. Five groups of the malnourished weanling rats were rehabilitated for 4 weeks with identical diets containing either soybean, peanut, sesame, palm or coconut oils, respectively. Adequacy of EFA in the diets improved appetite and food intake during rehabilitation. Coconut oil was least effective in growth recovery. Previous malnutrition left permanent growth stunting and deficits in the size of organs. Palm oil produced the highest concentration of plasma cholesterol while coconut oil produced the highest concentration of phospholipids. Total lipid and phospholipid concentrations were adversely affected by malnutrition, but in rehabilitated rats the response varied with the type of tissue and source of dietary lipids. The fatty acid profiles of phosphatidyl choline (PC) and phosphatidyl ethanolamine (PE) of the brain and liver were adversely affected by malnutrition, but in the rehabilitated rats, PC and PE fatty acids varied with the level of EFA, type of tissue and source of dietary lipids. Overall, post-malnutrition rehabilitation did not correct all the damage imposed by malnutrition. Recovery, in qualitative and quantitative terms, varied with the type of tissue and dietary lipid fed, and was related positively to the levels of EFA in the diets.     

Zinc status affects neurotransmitter activity in the paraventricular nucleus of rats

Alterations in neurochemical activity in the paraventricular nucleus (PVN) of the hypothalamus may account for decreased intake of zinc-deficient diets. Male Sprague-Dawley rats were fed zinc-deficient (ZD) or zinc-adequate (ZA) diet for 14 d before samples of extracellular fluid in the PVN were collected by microdialysis or push-pull perfusion. A third set of rats was pair-fed (PF) an amount of ZA diet equal to the intake of ZD rats. Samples were collected over a 2-h period spanning the transition from light to dark. All rats then consumed the zinc adequate diet ad libitum for 3 d before a second set of samples was collected. The increase in extracellular norepineprhrine (NE) during h 1 of the dark period to 147 +/- 13% of baseline (P < 0.05) was apparent only in ZA rats at d 14. After the 3-d repletion period, the increase in NE at dark onset occurred in all three groups. An increase in extracellular neuropeptide Y (NPY) at dark onset to 174 +/- 32% of baseline in rats fed ZA (P < 0.01) was measured in all three groups at both d 14 and 17. Basal NPY concentrations were significantly elevated in PF rats on d 14 (7.45 +/- 2.01 vs. 0.58 +/- 0.23 pmol/L, P = 0.01) and returned to ZA levels by d 17. The activities of the NE and NPY systems in the PVN were altered in rats fed a zinc-deficient diet; however, it is unclear whether the disruption in the NE and NPY neural systems in the PVN results in the altered feeding behavior accompanying zinc deficiency.     

Retinal and lens damages observed in young rats undergoing protein malnutrition in selected stages of their growth

Ocular damages of young rats undergoing protein malnutrition in selected stages of their growth have been valuated. Malnutrition was induced by a purified, hypoproteinic diet given to mothers or to newborns after their weaning. The histologic results pointed out that protein lack damages ocular structures different in embryonal origin: retina and lens. In fact, vacuolar degeneration of retinal optic fiber layer and cataract of lens were observed in experimental groups of rats. Only lens damage appeared completely reversible after a prolonged nutritional rehabilitation as for rats malnourished during fetal stage and lactation and then rehabilitated for 50 days. On the contrary retinal degeneration was still present in these animals even if some improvement could be observed.     

Effect of the duration of malnutrition and of nutritional rehabilitation on blood glucose homeostasis and pancreatic hormones in rats

1. To study the efficiency of rehabilitation after different periods of protein-energy malnutrition, we used as a model preweaning malnourished rats. After weaning, male Wistar rats were fed on a protein-deficient diet (50 g casein/kg) ad lib. for the whole study (DR group) or rehabilitated with normal diet (180 g casein/kg; RR group) from weaning, week 0, or weeks 1, 3, 5, 8 and 16 thereafter. 2. Twelve animals from the DR group were killed at the beginning of each rehabilitation period. The twelve rehabilitated rats were killed after 2 weeks. Body-weight and epididymal adipose tissue weight, blood glucose, plasma immunoreactive insulin (IRI) and immunoreactive glucagon (IRG), and pancreatic contents of IRI and IRG were determined. 3. Food intake of RR rats rose significantly except during the last period where body-weight increased less than that during the previous period. Fat-pad weights increased in the same manner in DR and RR groups. 4. Blood glucose fell and plasma IRG rose significantly without any change in plasma IRI after each rehabilitation period, except during the last period where blood glucose concentrations became stable. Pancreatic IRG and IRI showed the same type of response to those of the plasma. 5. All short-term rehabilitation periods were similarly efficient at producing catch-up growth. High insulin sensitivity of target cells was responsible for good recovery except after long-term malnutrition.     

Hyperphagia in obesity is associated with a central peptidergic dysregulation in rats

Hyperphagia and obesity are often associated, and the origins of the biochemical modifications leading to these syndromes might be in the hypothalamus. Indeed, food intake is regulated by numerous neuropeptides in various hypothalamic nuclei, including the paraventricular (PVN), arcuate (ARC), ventromedian (VMN) and suprachiasmatic (SCH) nuclei. Among these peptides, neuropeptide Y (NPY) is the most potent inducer of food intake whereas neurotensin (NT) decreases food intake. We measured these two peptides in microdissected hypothalamic nuclei in obese Zucker rats that ate 30% more food than their lean counterparts. Neuropeptide Y and neurotensin levels varied in opposite directions: In the hyperphagic obese Zucker rats, the NPY concentrations were significantly greater than those in the lean normophagic rats in the ARC (+30%), PVN (+60%) and SCH (+94%) nuclei, whereas the NT levels were significantly lower in the ARC (-40%), PVN (-31%) VMN (-66%) and SCH (-47%) nuclei. Both these variations tend to increase food intake. Feeding periodicity might also be modified because large variations of the two peptides have been measured in the supra-chiasmatic nucleus, which is considered the most important regulator of feeding rhythm. The results reinforce the hypothesis that hyperphagia in obesity is associated with a biochemical modification in the central nervous system because the peripheral status of NT and NPY was not modified in the obese rats. Because levels of other hypothalamic peptides, such as opioid peptides and somatostatin, are also slightly modified, it can be concluded that hyperphagia in obesity is associated with a central peptidergic dysregulation. Research on drugs reacting specifically with the receptor of these peptides might have interesting implications for the treatment of hyperphagia and, therefore, of obesity.     

Cross-fostering to diabetic rat dams affects early development of mediobasal hypothalamic nuclei regulating food intake, body weight, and metabolism

Exposure to maternal gestational diabetes (GD) "programs" offspring for obesity in childhood and later life. Recent clinical data suggest that neonatal ingestion of breast milk from diabetic mothers might be crucially involved. Mediobasal hypothalamic nuclei such as the ventromedial nucleus (VMN), the paraventricular nucleus (PVN) and the arcuate nucleus (ARC) play a key role in the central nervous system regulation of food intake and body weight. In the ARC, orexigenic neuropeptides such as neuropeptide Y (NPY), galanin (GAL), and agouti-related peptide (AGRP) and anorexigenic neuropeptides such as proopiomelanocortin (POMC) and alpha-melanocyte-stimulating hormone (MSH) are expressed. We investigated the effects of neonatal exposure to milk from GD rat dams on the development of hypothalamic nuclei in weanling rats. Offspring of control (CO) rat dams cross-fostered to GD rat dams (CO-GD) developed early postnatal growth delay. On d 21 of life, CO-GD rats showed structural and functional hypothalamic "malprogramming." The ARC of CO-GD rats showed increased immunopositivity of both NPY and AGRP under basal conditions, despite normal levels of glucose, leptin, and insulin. Conversely, CO-GD rats showed decreased immunopositivity of both POMC and MSH and decreased density of immunopositive neurons, compared with offspring of control rat dams cross-fostered to control rat dams. No morphometric alterations were found in the VMN, whereas CO-GD rats showed an increased total number of neurons in the PVN. In summary, neonatal exposure to maternal diabetes through the intake of dam's milk in rats leads to a complex malprogramming of hypothalamic orexigenic and anorexigenic circuits that are critically involved in the lifelong regulation of food intake, body weight, and metabolism.     

Nutritional status and clinical outcomes of older patients in rehabilitation

BACKGROUND: Malnutrition is associated with poor outcomes in older adults and those admitted to rehabilitation may be particularly at risk. Objective To assess the nutritional status and outcomes of older adults in rehabilitation. SUBJECTS AND METHODS: We recruited 133 adults > or = 65 years from consecutive rehabilitation admissions. Nutritional status was assessed using the mini nutritional assessment, body mass index (BMI) and corrected arm muscle area (CAMA). Outcomes measured included length of stay, admission to higher level care, function and quality of life (QOL). RESULTS: Sixty-two (47%) subjects were well nourished, 63 (47%) at risk of malnutrition and eight (6%) malnourished. Twenty-two (17%) and 27 (20%) were below the desirable reference values for BMI and CAMA respectively. Subjects at risk of malnutrition/malnourished had longer length of stay (P = 0.023) and were more likely to be admitted to higher level care (P < 0.05). These subjects also had poorer function on admission (P < 0.001) and 90 days (P = 0.002) and QOL on admission (P < 0.008) and 90 days (P = 0.001). Those with low CAMA were twice as likely to be admitted to higher level care (P < 0.05) and had poorer function at 90 days (P = 0.017). CONCLUSIONS: Over half our sample was identified as at risk of malnutrition or malnourished and this was associated with poorer clinical outcomes.     

Predictors of ethanol consumption in adult Sprague-Dawley rats: relation to hypothalamic peptides that stimulate ethanol intake

To investigate mechanisms in outbred animals that increase the propensity to consume ethanol, it is important to identify and characterize these animals before or at early stages in their exposure to ethanol. In the present study, different measures were examined in adult Sprague-Dawley rats to determine whether they can predict long-term propensity to overconsume ethanol. Before consuming 9% ethanol with a two-bottle choice paradigm, rats were examined with the commonly used behavioral measures of novelty-induced locomotor activity and anxiety, as assessed during 15 min in an open-field activity chamber. Two additional measures, intake of a low 2% ethanol concentration or circulating triglyceride (TG) levels after a meal, were also examined with respect to their ability to predict chronic 9% ethanol consumption. The results revealed significant positive correlations across individual rats between the amount of 9% ethanol ultimately consumed and three of these different measures, with high scores for activity, 2% ethanol intake, and TGs identifying rats that consume 150% more ethanol than rats with low scores. Measurements of hypothalamic peptides that stimulate ethanol intake suggest that they contribute early to the greater ethanol consumption predicted by these high scores. Rats with high 2% ethanol intake or high TGs, two measures found to be closely related, had significantly elevated expression of enkephalin (ENK) and galanin (GAL) in the hypothalamic paraventricular nucleus (PVN) but no change in neuropeptide Y (NPY) in the arcuate nucleus (ARC). This is in contrast to rats with high activity scores, which in addition to elevated PVN ENK expression showed enhanced NPY in the ARC but no change in GAL. Elevated ENK is a common characteristic related to all three predictors of chronic ethanol intake, whereas the other peptides differentiate these predictors, with GAL enhanced with high 2% ethanol intake and TG measures but NPY related to activity.     

Management of severe acute malnutrition in an urban nutritional rehabilitation center in Burkina Faso

BACKGROUND: Management of acute severe malnutrition greatly contributes to the reduction of childhood mortality rate. In developing countries, where malnutrition is common, number of acute severe malnutrition cases exceeds inpatient treatment capacity. Recent success of community-based therapeutic care put back on agenda the management of acute severe malnutrition. We analysed key issues of inpatient management of severe malnutrition to suggest appropriate global approach. METHODS: Data of 1322 malnourished children, admitted in an urban nutritional rehabilitation center, in Burkina Faso, from 1999 to 2003 were analyzed. The nutritional status was assessed using anthropometrics indexes. Association between mortality and variables was measured by relative risks. Kaplan-Meier survival curves and Cox model were used. RESULTS: From the 1322 hospitalized children, 8.5% dropped out. Daily weight gain was 10.18 (+/-7.05) g/kg/d. Among hospitalized malnourished children, 16% died. Patients were at high risk of early death, as 80% of deaths occurred during the first week. The risk of dying was highest among the severely malnourished: weight-for-height<-4 standard deviation (SD), RR=2.55 P<0,001; low MUAC-for-age, RR=2.05 P<0.001. Kaplan-Meier survival curves and Cox model showed that the variables most strongly associated with mortality were weight-for-height and MUAC-for-age. Among children discharged from the nutritional rehabilitation centre, 10.9% had weight-for-height<-3 SD. CONCLUSION: The nutrition rehabilitation centre is confronted with extremely ill children with high risk of death. There is need to support those units for appropriate management of acute severe malnutrition. It is also important to implement community-based therapeutic care for management of children still malnourished at discharge from nutritional rehabilitation centre. These programs will contribute to reduce mortality rate and number of severely malnourished children attending inpatient nutrition rehabilitation centers, by prevention and early management.     

Protein deficiency, but not zinc deficiency, reduces recovery of type 1 and type 2 muscle fibre diameters in the gastrocnemius muscle of growing rats

The present study examines the effects of protein- and energy-type malnutrition in combination with Zn deficiency on the growth, serum insulin-like growth factor-1 (IGF-1), gastrocnemius muscle mass and fibre diameter of growing rats during a deficiency phase followed by nutritional rehabilitation. Rats (3-weeks old) were randomly assigned to baseline, or Zn-deficient (Z, < 1 mg Zn/kg), protein-deficient (P, 20 g protein/kg), combined Zn- and protein-deficient (ZP), energy-deficient (E, feed intake pair-fed to Z) or control (C, 30 mg Zn/kg and 170 g protein/kg) groups for a 3-week deficiency phase, followed by a 3-week repletion phase with the control diet. ATPase histochemical staining at pH 9·4 was used to differentiate type 1 and type 2 muscle fibres. After the deficiency phase, the ZP and P groups had lower body weight and smaller gastrocnemius muscle mass than the Z and E groups. Type 1 and 2 muscle fibre diameters (T1- and T2-MFD, respectively) were reduced in the ZP, P and Z groups compared with the E and C groups. Serum Zn was reduced in the ZP, P and Z groups, but serum IGF-1 was lowest in the Z and E groups. After the repletion phase, T1-MFD did not recover in the P and E groups nor T2-MFD in the P group, despite the P and E groups having a better recovery of body weight. In summary, previous protein deficiency, but not Zn deficiency, limited the recovery of both T1- and T2-MFD during nutritional repletion. The quality of skeletal muscle recovery in the malnourished groups was not associated with body weight, muscle mass, serum Zn or IGF-1 concentrations.     

The mossy fiber system of the hippocampal formation is decreased by chronic and postnatal but not by prenatal protein malnutrition in rats

We tested in 70-day-old Sprague-Dawley rats, whether malnutrition imposed during different periods of hippocampal development produced deleterious effects on the total reference volume of the mossy fiber system. Animals were treated under four nutritional conditions: (a) well nourished; (b) prenatal protein malnourished; (c) chronic protein malnourished and (d) postnatal protein malnourished. Timm's stained material was used in coronal hippocampal sections (40 microm) to estimate--using the Principle of Cavalieri--the total reference volume of the mossy fiber system in each experimental group. Our results show that chronic and postnatal protein malnourished, but not prenatal malnourished rats, decrease the mossy fiber system and the total reference volume of the mossy fiber system are selectively vulnerable to the type of dietary restriction. Thus, chronic and posnatal protein malnutrition produce deleterious effects, but only rats under prenatal protein malnutrition were able to reorganize synapses in this plexus. These findings raise the possibility that chronic malnutrition, as a long-term stressful factor, might be an important paradigm to test structural hippocampal changes that produce physiological and pathophysiological effects, or the possibility to recover its function for nutritional rehabilitation.     

Children recovered from malnutrition exhibit normal insulin production and sensitivity

Protein-energy malnutrition promotes adaptive hormonal changes that result in stunting. A previous study showed that stunted children had increased insulin sensitivity and diminished pancreatic beta-cell function. The objectives of the present study were to analyse the glucose, insulin, homeostasis model assessment of insulin sensitivity (HOMA-S) and homeostasis model assessment of pancreatic beta-cell function (HOMA-B) levels after nutritional recovery. The recovered group (n 62) consisted of malnourished children after treatment at a nutrition rehabilitation centre. At the beginning of treatment their age was 2.41 (sd 1.28) and 2.31 (sd 1.08) years, weight-for-age Z score - 2.09 (sd 0.94) and - 2.05 (sd 0.55) and height-for-age Z score - 1.85 (sd 1.11) and - 1.56 (sd 0.90), for boys and girls respectively. The control group consisted of well-nourished children without treatment (n 26). After treatment, boys of the recovered group gained 1.29 (sd 1.06) Z scores of height-for-age and 1.14 (sd 0.99) Z scores of weight-for-age, and girls, 1.12 (sd 0.91) and 1.21 (sd 0.74) Z scores respectively. No differences were found between control and recovered groups in insulin levels for boys (P = 0.704) and girls (P = 0.408), HOMA-B for boys (P = 0.451) and girls (P = 0.330), and HOMA-S (P = 0.765) for boys and girls (P = 0.456) respectively. The present study shows that the changes observed previously in glucose metabolism and insulin were reverted in children who received adequate treatment at nutritional rehabilitation centres and showed linear catch-up.     

Effect of environmental enrichment during nutritional rehabilitation on body growth, blood parameters and cerebral cortical development of rats

Environmental enrichment has been reported to aid recovery from behavioral deficits associated with malnutrition in infants and young rats. This study investigated whether corresponding neuroanatomical changes could be detected. Rats were suckled either by well-fed dams or dams malnourished during lactation. At weaning, well-fed males were either housed in pairs (standard condition, SC) or 12 per large cage with toys (enriched condition, EC) and fed a 17% protein diet (SC control and EC control, respectively). Malnourished pups were fed either a 17% (rehabilitation; "rehab") or a 6% (low protein) protein diet and housed in the SC or EC environment (SC rehab, EC rehab, SC low protein, and EC low protein). After 30 d there were no differences in hematocrit, serum total protein and albumin levels between SC and EC animals. Rehab rats had significantly lower serum total protein and albumin levels than did controls. Cortical thickness and dendritic branching of occipital cortex pyramidal cells were evaluated. Early malnutrition did not permanently affect cortical thickness. EC rehab rats had thicker cortices than did SC rehab rats at almost all locations measured. SC rehab rats had fewer high order dendrites than did SC controls. The difference in dendritic branching between EC and SC rats was 44% among rehab rats, 21% among controls and 11% (not significant) among low protein-fed rats. Environmental enrichment during nutritional rehabilitation enhances dendritic branching and thickness of the occipital cortex.     

Vitamin E does not modulate plasma lipid profile or C-reactive protein despite suppressing oxidative stress in orchiectomized rats

Vitamin E is known to improve antioxidant status and to prevent lipoprotein oxidation. However, the effect of vitamin E on other cardiovascular risk factors, including C-reactive protein (CRP) and lipid profile status, in orchiectomized rats is unknown. In the present study, 32 1-year-old male rats were randomized into two groups: a sham-control group (n = 8) and an orchiectomized group (n = 24). The orchiectomized group was divided into three groups of eight and assigned to one of the following treatments: orchiectomy (ORX), ORX + vitamin E mixture (65.6 mg/kg) diet, or ORX + vitamin E mixture (656 mg/kg) diet. For 120 days all four groups consumed a basal AIN-93M diet, while the vitamin E groups ate diets containing an additional vitamin E mixture. Four months after the study began, all the rats were killed, the blood was collected, and the plasma was assayed for antioxidant status, CRP, lipid profile, and indices of peroxidation. ORX decreased (P < .05) the plasma antioxidant status, superoxide dismutase (SOD) activity, and CRP level and increased (P < .05) the plasma malondialdeyde, nitrite, and lipid profile compared with that of the sham-control group. In contrast to the ORX group, supplementation with vitamin E mixture increased (P < .05) plasma antioxidant status and dose-dependently increased (P < .05) SOD activity, while the vitamin E decreased (P < .05) plasma malondialdeyde and nitrite. The vitamin E mixture had no effect on CRP or on lipid profiles when compared to the orchiectomized rats. In conclusion, vitamin E appears to reduce oxidative stress without modulating lipid profile or inflammatory response.     

The Mossy Fiber System of the Hippocampal Formation is Decreased by Chronic and Postnatal but not by Prenatal Protein Malnutrition in Rats

Abstract

We tested in 70-day-old Sprague-Dawley rats, whether malnutrition imposed during different periods of hippocampal development produced deleterious effects on the total reference volume of the mossy fiber system. Animals were treated under four nutritional conditions: (a) well nourished; (b) prenatal protein malnourished; (c) chronic protein malnourished and (d) postnatal protein malnourished. Timm's stained material was used in coronal hippocampal sections (40 μm) to estimate--using the Principle of Cavalieri--the total reference volume of the mossy fiber system in each experimental group. Our results show that chronic and postnatal protein malnourished, but not prenatal malnourished rats, decrease the mossy fiber system and the total reference volume of the mossy fiber system are selectively vulnerable to the type of dietary restriction. Thus, chronic and posnatal protein malnutrition produce deleterious effects, but only rats under prenatal protein malnutrition were able to reorganize synapses in this plexus. These findings raise the possibility that chronic malnutrition, as a long-term stressful factor, might be an important paradigm to test structural hippocampal changes that produce physiological and pathophysiological effects, or the possibility to recover its function for nutritional rehabilitation.