Protein Deprivation Research Articles

Postnatal growth velocity modulates alterations of proteins involved in metabolism and neuronal plasticity in neonatal hypothalamus in rats born with intrauterine growth restriction

Intrauterine growth restriction (IUGR) due to maternal protein restriction is associated in rats with an alteration in hypothalamic centers involved in feeding behaviour. In order to gain insight into the mechanism of perinatal maternal undernutrition in the brain, we used proteomics approach to identify hypothalamic proteins that are altered in their expression following protein restriction in utero. We used an animal model in which restriction of the protein intake of pregnant rats (8% vs. 20%) produces IUGR pups which were randomized to a nursing regimen leading to either rapid or slow catch-up growth. We identified several proteins which allowed, by multivariate analysis, a very good discrimination of the three groups according to their perinatal nutrition. These proteins were related to energy-sensing pathways (Eno 1, E 2PDH, Acot 1 and Fabp5), redox status (Bcs 1L, PrdX3 and 14-3-3 protein) or amino acid pathway (Acy1) as well as neurodevelopment (DRPs, MAP2, Snca). In addition, the differential expressions of several key proteins suggested possible shunts towards ketone-body metabolism and lipid oxidation, providing the energy and carbon skeletons necessary to lipogenesis. Our results show that maternal protein deprivation during pregnancy only (IUGR with rapid catch-up growth) or pregnancy and lactation (IUGR with slow postnatal growth) modulates numerous metabolic pathways resulting in alterations of hypothalamic energy supply. As several of these pathways are involved in signalling, it remains to be determined whether hypothalamic proteome adaptation of IUGR rats in response to different postnatal growth rates could also interfere with cerebral plasticity or neuronal maturation.

Macronutrient selection in Nile tilapia fed gelatin capsules and challenged with protein dilution/restriction

Most animals, including fish, are known to possess "nutritional wisdom" which allows them to choose among different incomplete diets to self-compose a nutritionally balanced diet. The purpose of this research was to investigate dietary selection and the capacity of fish to associate between colour code of encapsulated diets and capsule contents. In addition, fish were subjected to different challenges (changing the relative position of capsules and their content, and protein dilution/restriction) to test whether tilapia defended a given intake target of macronutrients and energy. To help fish discriminate between diets, different relationships between capsule colour and content were used. The results revealed a clear pattern of selection: 45.4% P, 32.2% C, and 22.4% L. After diluting or restricting the protein, fish increased their intake of protein capsules to compensate for the dilution or restriction in such a way that their energy intake remained around 170 kJ/kg BW. These results confirm that tilapia, an omnivorous fish model, can select from individual macronutrients to self-compose a balanced diet, and are also able to regulate energy intake after protein dilution and selective protein deprivation. Besides, dietary selection and food intake regulation is not based on the oral properties of the diets because fish were fed tasteless gelatin capsules, suggesting that fish can associate the colour of the capsules with its nutritional effect.

Stem Cell Dynamics in Response to Nutrient Availability

When nutrient availability becomes limited, animals must actively adjust their metabolism to allocate limited resources and maintain tissue homeostasis. However, it is poorly understood how tissues maintained by adult stem cells respond to chronic changes in metabolism. To begin to address this question, we fed flies a diet lacking protein (protein starvation) and assayed both germline and intestinal stem cells. Our results revealed a decrease in stem cell proliferation and a reduction in stem cell number; however, a small pool of active stem cells remained. Upon refeeding, stem cell number increased dramatically, indicating that the remaining stem cells are competent to respond quickly to changes in nutritional status. Stem cell maintenance is critically dependent upon intrinsic and extrinsic factors that act to regulate stem cell behavior. Activation of the insulin/IGF signaling pathway in stem cells and adjacent support cells in the germline was sufficient to suppress stem cell loss during starvation. Therefore, our data indicate that stem cells can directly sense changes in the systemic environment to coordinate their behavior with the nutritional status of the animal, providing a paradigm for maintaining tissue homeostasis under metabolic stress.

Dietary protein deprivation upregulates insulin signaling and inhibits gluconeogenesis in rat liver

This study was undertaken to elucidate the effects of dietary protein deprivation on glucose metabolism and hepatic insulin signaling in rats. The results of glucose and pyruvate tolerance tests in rats fed with a 12% casein diet (12C) and a protein-free diet (PF) indicated that protein deprivation enhanced clearance of blood glucose and suppressed gluconeogenesis. Correspondingly, the mRNA level of hepatic phosphoenolpyruvate carboxykinase, a key gluconeogenic enzyme, was suppressed by dietary protein deprivation. In PF-fed rats, total tyrosine phosphorylation of insulin receptor (IR) in the liver induced by insulin injection was enhanced compared with 12C pair-fed rats due to an increase in IR protein level. In addition, protein deprivation caused an increase in protein levels of IR substrate 1 (IRS1) and IRS2, leading to the marked enhancement of insulin-induced tyrosine phosphorylation of IRS2 and its binding to the p85 regulatory subunit of phosphatidylinositol 3-kinase (PI3K). Based on these results, we conclude that protein deprivation suppresses gluconeogenesis by a mechanism primarily mediated by the enhancement of the insulin signals through the IR/IRS/PI3K/mammalian target of rapamycin complex 1 pathway in the liver. Taken together with our previous report, these findings suggest that tissue-specific potentiation of insulin action in the liver and the skeletal muscle plays important roles in maintaining glucose homeostasis even when energy usage is reduced by dietary protein deprivation.

Nutritional state and collective motion: from individuals to mass migration.

In order to move effectively in unpredictable or heterogeneous environments animals must make appropriate decisions in response to internal and external cues. Identifying the link between these components remains a challenge for movement ecology and is important in understanding the mechanisms driving both individual and collective motion. One accessible way of examining how internal state influences an individual's motion is to consider the nutritional state of an animal. Our experimental results reveal that nutritional state exerts a relatively minor influence on the motion of isolated individuals, but large group-level differences emerge from diet affecting inter-individual interactions. This supports the idea that mass movement in locusts may be driven by cannibalism. To estimate how these findings are likely to impact collective migration of locust hopper bands, we create an experimentally parametrized model of locust interactions and motion. Our model supports our hypothesis that nutrient-dependent social interactions can lead to the collective motion seen in our experiments and predicts a transition in the mean speed and the degree of coordination of bands with increasing insect density. Furthermore, increasing the interaction strength (representing greater protein deprivation) dramatically reduces the critical density at which this transition occurs, demonstrating that individuals' nutritional state could have a major impact on large-scale migration.

Evidence That Prenatal Programming of Hypertension by Dietary Protein Deprivation Is Mediated by Fetal Glucocorticoid Exposure

Prenatal programming by maternal dietary protein deprivation and prenatal dexamethasone result in a reduction in nephron number and hypertension when the offspring are studied as adults. To determine whether prenatal dietary protein deprivation results in a reduction in nephron number and hypertension in offspring by exposure to maternal glucocorticoids, we administered metyrapone to rats fed either a 6% or 20% protein diet to inhibit glucocorticoid production and compared the offspring to rats that were the product of mothers fed either a 6% or 20% protein diet during the last half of pregnancy. Male offspring from the 6% group had elevated systolic blood pressure (149 ± 2 vs. 130 ± 5 mm Hg, P < 0.05) and a reduction in glomeruli compared to the 20% group (22,111 ± 627 vs. 29,666 ± 654 glomeruli/kidney, P < 0.001). Maternal metyrapone administration did not affect the blood pressure in the 20% group but ameliorated the increase in blood pressure in the 6% male group to values comparable to the 20% control group (138 ± 6 vs. 130 ± 5 mm Hg). Male offspring of the 6% group that received metyrapone had an increase in the number of glomeruli compared to the vehicle-treated 6% group (26,780 ± 377 vs. 22,111 ± 627 glomeruli/kidney, P < 0.001), but less glomeruli compared to the 20% protein control group (26,780 ± 377 vs. 29,666 ± 654 glomeruli/kidney, P = 0.01). The reduction in nephron number and hypertension induced by maternal protein deprivation in male offspring is ameliorated by inhibition of glucocorticoid production.

Antenatal Protein Deprivation in the Mouse: Epigenetic Changes and Developmental Origin of Hypertension in Adult

As a consequence of antenatal maternal low protein diet (AMLPD), studies report changes in the renin‐angiotensin system (RAS), which may be involved in fetal programming of hypertension. We tested the hypothesis that AMLPD may cause epigenetic modifications and altered miRNA regulation of the RAS genes leading to developmental programming of hypertension in the adult mice offspring. We administered isocaloric, normal, 50% (moderate AMLPD) and 33% (severe AMLPD) diet, starting 1 week before mating and continued until delivery of the pups. We measured blood pressure (BP), promoter DNA methylation, mRNA, miRNA, proteins from the mice brain at fetal, 3 weeks and 33 weeks of age. Birth weight was significantly reduced, but there was a rapid catch‐up growth with AMLPD. Both moderate and severe AMLPD lead to significant increase in BP in male and female mice. In both fetal and adult AMLPD brain, we observed an increase in ACE mRNA levels. However, in the fetus increased ACE mRNA was not associated with increased protein levels. miRNA mmu‐mir‐27a increased significantly in fetus from moderate AMLPD group, which can lead to decrease in ACE protein translation. We also observed hypomethylation of DNA promoter of ACE, which can increase mRNA transcription. Overall, our results indicate that AMLPD can lead to epigenetic changes in brain ACE with associated hypertension in adult offspring.

Effects of pre- and postnatal protein deprivation and postnatal refeeding on atrial natriuretic peptide (ANP) granules of auricular cardiocytes

Background & aims: Atrial natriuretic peptide (ANP-granules) of auricular cardiocytes was examined by morphometry in undernourished and refed rats. Methods: The study was conducted on 21 and 42-day-old rats from mothers exposed to 73% protein restriction during the gestation and lactation with and without refeeding and on age-matched control animals. The body and the heart were weighted and the ANP-granules are located by transmission electron microscopy. Results: Protein deprivation in the 42 postnatal days reduced the body weights and the heart weights of the pups. Refeeding did not restore body weight or heart weight to control. In the undernourished group, the number of ANP-granules/field (27.3 ± 6.22) was significantly (p < 0.05) greater at 42 days than in the control (10.5 ± 1.89). In the refed group, the number of ANP-granules was also significantly greater, than that in the group on undernutrition. The diameter of ANP-granules in the undernourished animals was similar to the refed rats at 42 days and significantly greater than in the control (p < 0.05). Conclusion: Refeeding between 21 and 42 days increased the number of ANP-granules and maintained their diameter even when there is a reduction in heart weight caused by protein deprivation. © 2010 European Society for Clinical Nutrition and Metabolism.

Effects of perinatal protein deprivation and recovery on esophageal myenteric plexus

To evaluate effects of pre- and postnatal protein deprivation and postnatal recovery on the myenteric plexus of the rat esophagus. Three groups of young Wistar rats (aged 42 d) were studied: normal-fed (N42), protein-deprived (D42), and protein-recovered (R42). The myenteric neurons of their esophagi were evaluated by histochemical reactions for nicotinamide adenine dinucleotide (NADH), nitrergic neurons (NADPH)-diaphorase and acetylcholinesterase (AChE), immunohistochemical reaction for vasoactive intestinal polypeptide (VIP), and ultrastructural analysis by transmission electron microscopy. The cytoplasms of large and medium neurons from the N42 and R42 groups were intensely reactive for NADH. Only a few large neurons from the D42 group exhibited this aspect. NADPH detected in the D42 group exhibited low reactivity. The AChE reactivity was diffuse in neurons from the D42 and R42 groups. The density of large and small varicosities detected by immunohistochemical staining of VIP was low in ganglia from the D42 group. In many neurons from the D42 group, the double membrane of the nuclear envelope and the perinuclear cisterna were not detectable. NADH and NADPH histochemistry revealed no group differences in the profile of nerve cell perikarya (ranging from 200 to 400 microm(2)). Protein deprivation causes a delay in neuronal maturation but postnatal recovery can almost completely restore the normal morphology of myenteric neurons.

Effects of protein deprivation and re-feeding on P2X2receptors in enteric neurons

To investigate the effects of malnutrition and re-feeding on the P2X(2) receptor, nitric oxide synthase (NOS), calretinin, calbindin and choline acetyltransferase (ChAT) in neurons of the rat ileum. We analyzed the co-localization, numbers and sizes of P2X(2)-expressing neurons in relation to NOS-immunoreactive (IR), calbindin-IR, ChAT-IR, and calretinin-IR neurons of the myenteric and submucosal plexus. The experimental groups consisted of: (1) rats maintained on normal feed throughout pregnancy until 42 d post-parturition (N); (2) rats deprived of protein throughout pregnancy and 42 d post-parturition (D); and (3) rats undernourished for 21 d post-parturition and then given a protein diet from days 22 to 42 (DR). The myenteric and submucosal plexuses were evaluated by double labeling by immunohistochemical methods for P2X(2) receptor, NOS, ChAT, calbindin and calretinin. We found similar P2X(2) receptor immunoreactivity in the cytoplasm and surface membranes of myenteric and submucosal neurons from the N, D and DR groups. Double labeling of the myenteric plexus demonstrated that approximately 100% of NOS-IR, calbindin-IR, calretinin-IR and ChAT-IR neurons in all groups also expressed the P2X(2) receptor. In the submucosal plexus, the calretinin-IR, ChAT-IR and calbindin-IR neurons were nearly all immunoreactive for the P2X(2) receptor. In the myenteric plexus, there was a 19% increase in numbers per cm(2) for P2X(2) receptor-IR neurons, 64% for NOS-IR, 84% for calretinin-IR and 26% for ChAT-IR neurons in the D group. The spatial density of calbindin-IR neurons, however, did not differ among the three groups. The submucosal neuronal density increased for calbindin-IR, calretinin-IR and ChAT-IR neurons. The average size of neurons in the myenteric plexus neurons in the D group was less than that in the controls and, in the re-fed rats; there was a 34% reduction in size only for the calretinin-IR neurons. This work demonstrates that expression of the P2X(2) receptor is present in inhibitory, intrinsic primary afferent, cholinergic secretomotor and vasomotor neurons. Undernutrition affected P2X(2) receptor expression in the submucosal plexus, and neuronal and size. These changes were rescued in the re-fed rats.

The relative effects of severe burn injury and pre- and post-natal protein deprivation on mandibular condyle morphology

The mandible has a mixed embryological origin, and its growth is associated with the secondary cartilage of the condyle process (CP). In this area, growth depends on an array of intrinsic and extrinsic factors that influence protein metabolism. In the present study, we used an adolescent rat model to evaluate the growth and development of the CP under conditions of pre- and postnatal protein deficiency, combined with or without the stress of severe burn injury (BI). We found that protein deficiency severely undermined the growth of the CP, by altering the thickness of its constituent layers. BI is also capable of affecting CP growth, although the effect is less severe than protein deficiency. Interestingly, the summed effect of protein deficiency and BI on the CP is less severe than protein deficiency alone. A possible explanation is that the increased carbohydrates in a hypoproteic diet stimulate the production of endogenous insulin and protein synthesis, which partially compensates for the loss of lean body mass caused by BI.

PTH improves titanium implant fixation more than pamidronate or renutrition in osteopenic rats chronically fed a low protein diet

We evaluated the effects of parathyroid hormone (PTH), pamidronate, or renutrition on osseointegration of titanium implants in the proximal tibia of rats subject to prolonged low-protein diets. PTH improved mechanical fixation, microarchitecture, and increased pull-out strength. Pamidronate or renutrition had lesser effects. PTH can thus improve implant osseointegration in protein-malnourished rats. Protein malnutrition impairs implant osseointegration in rats. PTH and pamidronate prevent deleterious effects of protein restriction introduced just prior to implantation. Whether these treatments improve osseointegration after chronic protein deprivation, i.e., in osteopenic bone at time of implantation, is unknown. We evaluated effects of PTH, pamidronate, or renutrition on resistance to pull-out of titanium rods implanted into the rat tibiae following isocaloric low-protein intake. Forty-one adult female rats received normal or isocaloric low-protein diets. Six weeks later, implants were surgically inserted into proximal tibiae. Following implantation, rats on low-protein diets were treated with PTH (1-34), pamidronate, saline vehicle, or normal protein diets, for another 8 weeks. Tibiae were removed for micro-computerised tomographic morphometry and evaluation of pull-out strength. Pull-out strength decreased in rats on isocaloric low-protein diets compared with normal protein group (-33.4%). PTH increased pull-out strength in low-protein group, even compared to controls from the normal protein group. PTH and pamidronate increased bone volume/tissue volume, bone-to-implant contact, and trabecular thickness, whilst trabecular separation was reduced, with a shift to more plate-like bone surrounding the implants. PTH reversed the deleterious effects of long-term protein undernutrition on mechanical fixation and bone microarchitecture and improved implant osseointegration more than pamidronate or renutrition, likely through changes to structure model index.

Maternal Protein Restriction During Early Lactation Induces Changes on Neutrophil Activation and TNF-α Production of Adult Offspring

Maternal nutritional environmental in early life has been often associated with long term effects on the immune response in adulthood. The effects of maternal protein deprivation during early lactation on neutrophil-mediated innate immunity were investigated in adult rats, offspring of dams fed with a protein-free diet during the first days of lactation (PD), and compared to controls (22% protein diet). Inflamed PD animals showed an inhibited neutrophil migration and an impaired recruitment of leukocytes from bone marrow pool to circulation. In resting conditions, blood neutrophils from PD present reduced phagocytic activity, increased production of O(2) (-) and NO, basal iNOS expression and constitutive NF-kappaB activation. Moreover, PD rats also show high circulating levels of TNF-alpha and increased expression of TNF-alpha mRNA in the spleen and liver. The data indicate that maternal nutritional stress can interfere on the innate immune response in adulthood, imprinting permanent alterations on cytokine production and neutrophil activation.

Role of the kidney in the prenatal and early postnatal programming of hypertension

Epidemiologic studies from several different populations have demonstrated that prenatal insults, which adversely affect fetal growth, result in an increased incidence of hypertension when the offspring reaches adulthood. It is now becoming evident that low-birth-weight infants are also at increased risk for chronic kidney disease. To determine how prenatal insults result in hypertension and chronic kidney disease, investigators have used animal models that mimic the adverse events that occur in pregnant women, such as dietary protein or total caloric deprivation, uteroplacental insufficiency, and prenatal administration of glucocorticoids. This review examines the role of the kidney in generating and maintaining an increase in blood pressure in these animal models. This review also discusses how early postnatal adverse events may have repercussions in later life. Causes for the increase in blood pressure by perinatal insults are likely multifactorial and involve a reduction in nephron number, dysregulation of the systemic and intrarenal renin-angiotensin system, increased renal sympathetic nerve activity, and increased tubular sodium transport. Understanding the mechanism for the increase in blood pressure and renal injury resulting from prenatal insults may lead to therapies that prevent hypertension and the development of chronic kidney and cardiovascular disease.

Maternal Protein Deprivation: Changes in Systemic Renin-Angiotensin System of the Mouse Fetus

We tested the hypothesis that maternal protein deprivation during gestation results in changes in expression of the systemic renin-angiotensin system in fetal mice. Fetal weight was decreased significantly as a consequence of 50% maternal protein deprivation during second half of gestation. In fetal liver, angiotensinogen protein expression was reduced significantly despite a significant increase in messenger RNA (mRNA). In fetal kidneys, both mRNA and protein levels of renin were increased significantly. In the lungs, we observed a decrease in both angiotensin-converting enzyme I and II mRNA expression, whereas protein expression of both isoforms was increased significantly. The fetal heart showed significant increases in expression of angiotensin II type 1 (AT-1) and type 2 (AT-2) receptors mRNA. Protein expression of AT-1 receptors increased, while that of AT-2 receptors decreased. We conclude that maternal low-protein diet during gestation leads to significant changes in expression of the systemic renin-angiotensin system in fetal mice and may be important in the genesis of hypertension in the adult.

Prenatal programming of rat thick ascending limb chloride transport by low-protein diet and dexamethasone

Prenatal administration of dexamethasone and a low-protein diet has been shown to result in hypertension in the offspring when they are adults. The cause for the hypertension is unknown. The purpose of this study was to examine whether there was prenatal programming of thick ascending limb transport. Rats were administered either dexamethasone for 4 days (0.2 mg/kg body wt) by intraperitoneal injection daily between the 15th and 18th day of gestation, or they were fed a low-protein diet (6% protein) or an isocaloric normal protein diet (20% protein) from day 12 gestation until birth. The offspring were studied as adults. Prenatal dexamethasone and dietary protein deprivation resulted in an increase in blood pressure. Offspring of mothers fed a low-protein diet had an increase in medullary but not cortical bumetanide-sensitive Na-K-2Cl cotransporter (NKCC2) protein abundance (P < 0.01). There was not a statistically significant increase in medullary NKCC2 by prenatal dexamethasone (P = 0.07). Both prenatal administration of dexamethasone and a low-protein diet resulted in an increase in medullary thick ascending limb chloride transport compared with control (298 +/- 33 pmoles x mm(-1) x min(-1), 280 +/- 26 pmoles x mm(-1) x min(-1), and 191 +/- 21 pmoles x mm(-1) x min(-1), respectively P < 0.05). There was a higher lumen-positive transepithelial potential difference in the prenatal dexamethasone and low-protein group compared with control as well. Administration of furosemide for 24 h resulted in a decrease in blood pressure in the low-protein group but not the control group. This study demonstrates that insults administered to the fetus can program altered sodium transport. Increased tubular sodium transport is a likely cause for the hypertension by prenatal programming.

Intestinal development affected by prenatal protein deprivation.

Journal Article Intestinal Development Affected by Prenatal Protein Deprivation Get access Nutrition Reviews, Volume 36, Issue 6, June 1978, Pages 191–193, https://doi.org/10.1111/j.1753-4887.1978.tb03752.x Published: 01 June 1978

Immunobiochemical status of sheep exposed to periods of experimental protein deficit and realimentation

Immunobiochemical status of sheep exposed to periods of experimental protein deficit and realimentation was studied in 12 sheep (15 mo) randomly distributed into 2 equal groups and fed individually 2 different concentrate supplements along with wheat straw to provide 100% (normal protein, NP) or 50% (low protein, LP) of CP requirements. The study was comprised of 3 periods; during period 1 (0 to 13 wk) and 2 (14 to 26 wk) animals in the 2 groups were fed NP and LP diets, respectively; during period 3 (27 to 44 wk), animals in the LP group were switched over to NP diet to allow realimentation, whereas animals in the NP group remained on the same NP diet. Blood was collected from all groups at end of each period, and serum glucose, total protein, albumin (sAlb), globulin (sGlb), urea (sU), creatinine (sCr), cholesterol, triiodothyronine, and thyroxine concentrations were determined. During the same periods, the cell-mediated immune (CMI) response was measured by a delayed type hypersensitivity (DTH) assay and in vitro nitrite production by lymphocytes. At the end of periods 2 and 3, humoral immune response (HIR) was measured by sensitizing the sheep with Brucella abortus S99 antigen and measuring antibody titers on 0, 7, 14, 21, and 28 d postinoculation by ELISA. Feed intake decreased with prolonged protein deficit and showed recovery during period 3. Blood chemistry revealed reduced sAlb concentration in the LP group resulting in narrow sAlb:sGlb ratio, increased sCr concentrations (P = 0.008) accompanying a decreased (P = 0.004) sU:sCr ratio, and decreased glucose concentrations (P = 0.05). Other variables did not change significantly between the NP and LP groups. The DTH response at the end of period 1 and 2 showed marked (P = 0.008) effect of protein restriction on CMI. Nitrite production, basal and after lipopolysaccharide stimulation, was greater (P = 0.04) in the NP group. The HIR was less (P = 0.04) in the LP group during period 3. Realimentation of protein in the LP group during period 3 showed recovery in CMI and HIR. In conclusion, protein deprivation induced a decline in CMI and HIR in sheep accompanying alterations in related metabolic profile. However, a marked recovery was observed after realimentation.

Placental Gene Expression Responses to Maternal Protein Restriction in the Mouse

Objective Maternal protein restriction has been shown to have deleterious effects on placental development, and has long-term consequences for the progeny. We tested the hypothesis that, by the use of microarray technology, we could identify specific genes and cellular pathways in the developing placenta that are responsive to maternal protein deprivation, and propose a potential mechanism for observed gene expression changes. Methods We fed pregnant FVB/NJ mice from day post-coitum 10.5 (DPC10.5) to DPC17.5, an isocaloric diet containing 50% less protein than normal chow. We used the Affymetrix Mouse 430A_2.0 array to measure gene expression changes in the placenta. We functionally annotated the regulated genes, and examined over-represented functional categories and performed pathway analysis. For selected genes, we confirmed the microarray results by use of qPCR. Results We observed 244 probe sets, corresponding to 235 genes, regulated by protein restriction ( p < 0.001), with ninety-one genes being up-regulated, and 153 down-regulated. Up-regulated genes included those involved in the p53 pathway, apoptosis, negative regulators of cell growth, negative regulators of cell metabolism and genes related to epigenetic control. Down-regulated genes included those involved in nucleotide metabolism. Conclusions Microarray analysis has allowed us to describe the genetic response to maternal protein deprivation in the mouse placenta. We observed that negative regulators of cell growth and metabolism in conjunction with genes involved in epigenesis were up-regulated, suggesting that protein deprivation may contribute to growth restriction and long-term epigenetic changes in stressed tissues and organs. The challenge will be to understand the cellular and molecular mechanisms of these gene expression responses.

Impact of Pre and Postnatal Protein Energy Deprivation on Structure of the Trigeminal Ganglion of Weanling Rats

The effects of protein energy deprivation (PED) on trigeminal ganglion sectional area, neuronal density, num- ber of neurons/section, neuronal body area and neuronal nucleus area were evaluated. The protein deprivation prenatally and for 21 days postnatally leads to reduce body weights (40% of control weights) and an increase in the number of neu- rons/section (35% more than control). Most neuron perikarya were within 400-600 � m 2 (53,7%) in protein-deprived ani- mals and 600-900 � m 2 (48,2%) in the control group. Rows of neuronal bodies were separated by bundles of nerve and col- lagen fibers in both groups. Ganglionic neurons from both groups contained cytoplasmic Nissl's corpuscles and spherical nuclei with eccentric and large nucleoli. The elongated nuclei of the fibrocytes revealed the main axis oriented parallel to the bundles nerve fibers. By scanning electron microscopy, the structure of the ganglion from both groups was found to be similar.