ABSTRACT
Maternal malnutrition results in learning deficits and predisposition to anxiety and depression in the offspring that extend into adulthood. At the cellular level, learning and memory rely on the production of new neurons in the dentate gyrus (DG) of the hippocampus, and hippocampal neurogenesis has been associated with the etiology and treatment of depression, but whether adult neurogenesis is affected by malnutrition during early life is not known. To investigate the effects of perinatal undernutrition on neurogenesis at adulthood, pregnant Sprague-Dawley rats were fed either ad libitum (C) or were undernourished by reducing their daily food intake by 50% in relation to the C group during gestation and lactation (FR/FR). At birth, one subset of control pups was cross-fostered to food-restricted dams to constitute a third group of animals that were undernourished during the lactation period only (AdLib/FR). At 90 days of age, pups were injected with bromodeoxyuridine (BrdU) and sacrificed 2 h, 1 week, or 3 weeks later. The number of BrdU-labeled cells in the DG was significantly reduced in the offspring of FR/FR dams in relation to controls at all the time points examined. However, the proportion of new cells exhibiting a neuronal phenotype was higher in FR/FR rats than in controls as revealed by the colabeling at 3 weeks of the BrdU-labeled cells with neuron-specific nuclear protein (NeuN). AdLib/FR animals exhibited also reduced BrdU labeling at 2 h and 1 week. Nevertheless, we found no significant differences at 3 weeks in either the number of BrdU-labeled cells or in the proportion of new neurons between controls and AdLib/FR rats. These results indicate that the decreased number of hippocampal neurons in perinatally undernourished rats is due to the deleterious effects of early nutrient restriction on cell proliferation but not on the neuronal differentiation process of the new generated cells.
Subject(s)
Cell Differentiation/physiology , Cell Proliferation , Fetal Nutrition Disorders/physiopathology , Hippocampus/cytology , Neurogenesis/physiology , Neurons/cytology , Prenatal Exposure Delayed Effects/physiopathology , Animals , Animals, Newborn , Body Weight/physiology , Disease Models, Animal , Eating/physiology , Female , Hippocampus/physiopathology , Humans , Male , Molecular Imaging/methods , Neurons/physiology , Pregnancy , Rats , Rats, Sprague-DawleyABSTRACT
OBJECTIVE: Several lines of evidence indicate that nutrient restriction during perinatal development sensitizes the offspring to the development of obesity, insulin resistance and cardiovascular disease in adulthood via the programming of hyperphagia and reduced energy expenditure. Given the link between the circadian clock and energy metabolism, and the resetting action of food on the circadian clock, in this study, we have investigated whether perinatal undernutrition affects the circadian expression rhythms of genes regulating food intake in the hypothalamus and energy metabolism in the liver. DESIGN: Pregnant Sprague-Dawley rats were fed ad libitum either a control (20% protein) or a low-protein (8% protein) diet throughout pregnancy and lactation. At weaning, pups received a standard diet and at 17 and 35 days of age, their daily patterns of gene expression were analyzed by real-time quantitative PCR experiments. RESULTS: 17-day-old pups exposed to perinatal undernutrition exhibited significant alterations in the circadian expression profile of the transcripts encoding diverse genes regulating food intake, the metabolic enzymes fatty acid synthase and glucokinase as well as the clock genes BMAL1 and Period1. These effects persisted after weaning, were associated with hyperphagia and mirrored the results of the behavioral analysis of feeding. Thus, perinatally undernourished rats exhibited an increased hypothalamic expression of the orexigenic peptides agouti-related protein and neuropeptide Y. Conversely, the mRNA levels of the anorexigenic peptides pro-opiomelanocortin and cocaine and amphetamine-related transcripts were decreased. CONCLUSION: These observations indicate that the circadian clock undergoes nutritional programming. The programming of the circadian clock may contribute to the alterations in feeding and energy metabolism associated with malnutrition in early life, which might promote the development of metabolic disorders in adulthood.
Subject(s)
Circadian Clocks/genetics , Diet, Protein-Restricted/adverse effects , Eating/genetics , Genes, Regulator/genetics , Prenatal Exposure Delayed Effects/genetics , Adaptation, Physiological , Analysis of Variance , Animals , Body Weight , Female , Gene Expression Regulation/physiology , Pregnancy , Prenatal Exposure Delayed Effects/physiopathology , Rats , Rats, Sprague-Dawley , Reverse Transcriptase Polymerase Chain Reaction , WeaningABSTRACT
PURPOSE: To determine the overall diagnostic accuracy of mononuclear leukocyte- 99mTc scintigraphy in the routine detection of infectious lesions and fever of unknown origin (FUO) in inpatients. MATERIAL AND METHODS: The use of mononuclear leukocyte 99mTc scintigraphy is presented in 87 patients who fulfilled the Durack and Street diagnostic criteria of nosocomial FUO; 66 patients were suspected of having infectious lesions (myocarditis, endocarditis, infected catheters, diabetic foot, and osteomyelitis) and 21 patients presented with unknown causes of FUO. Scans were carried out 1, 3, and 24 h after injection of labeled leukocytes. RESULTS: In three cases (3/27) where scintigraphs were negative, biopsies were positive. There were two (2/87) false-positive scintigrams. We found a 95.8% sensitivity and 92.3% specificity. PPV was 93.8%, PPN 94.7%, and accuracy 94.2%. CONCLUSION: Mononuclear leukocyte 99mTc scintigraphy showed high sensitivity, specificity, positive and negative predictive values in patients with nosocomial FUO. These results suggest an important role for nuclear medicine in the management of patients with infection/inflammation.
Subject(s)
Cross Infection/diagnostic imaging , Fever of Unknown Origin/diagnostic imaging , Leukocytes, Mononuclear/diagnostic imaging , Technetium , Adult , Aged , Aged, 80 and over , Chi-Square Distribution , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Radionuclide Imaging , Radiopharmaceuticals , Sensitivity and SpecificityABSTRACT
One hundred kidney transplant recipients were evaluated on the first and fifth days after transplantation by Tc-99m mononuclear cell scintigraphy. We have developed a quantitative method to diagnose rejection and acute tubular necrosis (ATN) by comparing regions of interest drawn on allograft scintigraphs at different times after endovenous administration of the labeled cells. We suggest that the use of Tc-99m-WBC may be useful for the early diagnosis of rejection and the differential diagnosis of ATN.