Expression of Hemoglobin in Rodent Neurons

Schelshorn, Dominik W.; Schneider, Armin; Kuschinsky, Wolfgang; Weber, Daniela; Krüger, Carola; Dittgen, Tanjew; Bürgers, Heinrich F.; Sabouri, Fatemeh; Gaßler, Nikolaus; Bach, A.; Maurer, Martin H.

doi:10.1038/jcbfm.2008.152

Cited by 132 publications

(136 citation statements)

References 39 publications

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“…Conversely, the highest upregulated transcripts in the DEX-IUGR hippocampus were the iron-containing oxygen-transport metalloproteins (Hba-a2 and Hbb). This "ectopic" expression, out of red blood cells, corroborates recent neuronal hemoglobin detection with an oxygen capacitator activity (38). It was also interesting to note that some transcripts of interest were upregulated in control pups born to bLf-supplemented dams, such as Ttr (a transport protein for retinol-binding protein/thyroxine, widely used as a clinical nutritional marker), Plp1 (a protein associated with myelin biogenesis/ compaction), Metrn (a neurotrophic factor), Ptma (a necrosis inhibitor) and Clu (a glycoprotein chaperone molecule).…”

Section: Maternal Lactoferrin For Iugr Ratssupporting

confidence: 53%

Protective effects of maternal nutritional supplementation with lactoferrin on growth and brain metabolism

et al. 2013

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Background: Intrauterine growth restriction (IUGR) is a major risk factor for both perinatal and long-term morbidity. Bovine lactoferrin (bLf ) is a major milk glycoprotein considered as a pleiotropic functional nutrient. The impact of maternal supplementation with bLf on IUGR-induced sequelae, including inadequate growth and altered cerebral development, remains unknown. Methods: IUGR was induced through maternal dexamethasone infusion (100 μg/kg during last gestational week) in rats. Maternal supplementation with bLf (0.85% in food pellet) was provided during both gestation and lactation. Pups growth was monitored, and pup brain metabolism and gene expression were studied using in vivo 1 H NMR spectroscopy, quantitative PCR, and microarray in the hippocampus at postnatal day (PND)7. results: Maternal bLf supplementation did not change gestational weight but increased the birth body weight of control pup (4%) with no effect on the IUGR pups. Maternal bLf supplementation allowed IUGR pups to recover a normalized weight at PND21 (weaning) improving catch-up growth. Significantly altered levels of brain metabolites (γ-aminobutyric acid, glutamate, N-acetylaspartate, and N-acetylaspartylglutamate) and transcripts (brain-derived neurotrophic factor (BDNF), divalent metal transporter 1 (DMT-1), and glutamate receptors) in IUGR pups were normalized with maternal bLf supplementation. conclusion: Our data suggest that maternal bLf supplementation is a beneficial nutritional intervention able to revert some of the IUGR-induced sequelae, including brain hippocampal changes.

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Section: Maternal Lactoferrin For Iugr Ratssupporting

confidence: 53%

Protective effects of maternal nutritional supplementation with lactoferrin on growth and brain metabolism

et al. 2013

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“…In contrast to the allelic differences in cysteine content that distinguish products of Hbb d and Hbb s in M. domesticus and M. musculus, amino acid differences between the d minor and p minor isoHbs of M. castaneus have no effect on the metabolism of thiol reactants or intraerythrocytic redox balance (which can affect aspects of the host immune response to pathogenic infection). Nonetheless, we cannot rule out the possibility that the b-globin polymorphism in M. castaneus affects some unknown biochemical function, especially in light of recent discoveries concerning the expression of globin chain monomers in nonerythroid cells (e.g., Liu et al 1999;Mansergh et al 2008;Nishi et al 2008;Biagioli et al 2009;Richter et al 2009;Schelshorn et al 2009). In light of our experimental results, we conclude that amino acid differences between products of the d minor and p minor alleles are functionally inconsequential with regard to the respiratory physiology of house mice.…”

Section: Discussionmentioning

confidence: 99%

Evolutionary and Functional Properties of a Two-Locus β-Globin Polymorphism in Indian House Mice

et al. 2010

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The main objectives of this study were (i) to characterize patterns of nucleotide polymorphism and linkage disequilibrium in the duplicated b-globin genes of M. castaneus, (ii) to test the hypothesis that the Hbb d and Hbb p haplotypes are maintained as a balanced polymorphism, and (iii) to assess whether allelic differences in the alternative minor Hb isoforms (d minor and p minor ) are associated with different O 2 -binding properties. A multilocus analysis of polymorphism and divergence revealed that levels of diversity at the HBB-T2 gene exceeded neutral expectations, and reconstructed haplotype networks for both b-globin paralogs revealed extensive allele sharing with several other closely related species of Mus. However, despite this suggestive evidence for balancing selection, O 2 -equilibrium curves revealed no discernible functional differences between red cell lysates containing the d minor and p minor Hb isoforms. If the d minor and p minor alleles are maintained as a balanced polymorphism, our results indicate that the associated fitness variance is not directly related to respiratory functions of Hb.B ALANCING selection at a particular locus is expected to produce elevated levels of nucleotide diversity and linkage disequilibrium (LD) due to the partitioning of sequence variation between unusually long-lived allele classes (Hudson and Kaplan 1988;Charlesworth et al. 2003;Charlesworth 2006). Although elevated levels of nucleotide polymorphism at a particular gene may provide suggestive evidence for a history of balancing selection, conclusive inferences regarding the selective maintenance of allelic polymorphism ultimately require experimental evidence that the alternative alleles are functionally distinct. The well-characterized b-globin polymorphism in house mice (genus Mus) represents a system where it is possible to integrate evolutionary and functional approaches to evaluate the role of balancing selection in maintaining protein polymorphism.The two tandemly duplicated b-globin genes of house mice, HBB-T1 and HBB-T2, encode the b-chain subunits of adult hemoglobin (Hb) (Petras 1967; Selander et al. 1969a,b;Selander and Yang 1969;Berry and Murphy 1970;Wheeler and Selander 1972;Myers 1974;Berry and Jakobson 1975;Berry and Peters 1975, 1977Berry et al. 1978;Sage 1981;Petras and Topping 1983;Sage et al. 1986). This striking uniformity of two-locus haplotype frequencies has led a number of authors to conclude that the polymorphism may be maintained by some form of balancing selection Sequence data from this article have been deposited in GenBank under accession nos. GU057161-GU057256. (Hutton et al. 1962;Gilman 1972Gilman , 1974Whitney 1977 /Hbbp polymorphism we conducted a population genetic analysis of the HBB-T1 and HBB-T2 genes in a natural population of M. castaneus from northern India. In conjunction with this evolutionary analysis of sequence variation, we also conducted an experimental study of Hb function in inbred strains of mice that carry each of the alternative two-locus b-globin h...

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“…84,85 In addition, EPO reduces cerebral hypoxia by up-regulating neuronal hemoglobin expression. 53 In addition to these actions, EPO is also anti-inflammatory. 34,35 These pleiotropic effects of EPO likely contribute to the improved survival in complex ways.…”

Section: Hypoxia and Cerebralmentioning

confidence: 99%

“…Optical sectioning (Video S1) demonstrated an example of one such area in which hypoxic cells in the brain parenchyma are adjacent to plugged vessels. The extent of cerebral hypoxia detected in CM mice likely causes impaired neuronal communication, 53 which in turn leads to cerebral debilitation and altered behavior. 55 A low degree of hypoxia could also be demonstrated as scattered, single, hypoxic cells in non-CM models without clinically obvious neurologic impairment, which suggests that even in the absence of cerebral signs, malaria may affect neural tissue.…”

Section: Hypoxia and Cerebralmentioning

confidence: 99%

CNS Hypoxia Is More Pronounced in Murine Cerebral than Noncerebral Malaria and Is Reversed by Erythropoietin

Hempel

Combes

Hunt

et al. 2011

The American Journal of Pathology

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Cerebral malaria (CM) is associated with high mortality and risk of sequelae, and development of adjunct therapies is hampered by limited knowledge of its pathogenesis. To assess the role of cerebral hypoxia, we used two experimental models of CM, Plasmodium berghei ANKA in CBA and C57BL/6 mice, and two models of malaria without neurologic signs, P. berghei K173 in CBA mice and P. berghei ANKA in BALB/c mice. Hypoxia was demonstrated in brain sections using intravenous pimonidazole and staining with hypoxia-inducible factor-1␣-specific antibody. Cytopathic hypoxia was studied using poly (ADP-ribose) polymerase-1 (PARP-1) gene knockout mice. The effect of erythropoietin, an oxygen-sensitive cytokine that mediates protection against CM, on cerebral hypoxia was studied in C57BL/6 mice. Numerous hypoxic foci of neurons and glial cells were observed in mice with CM. Substantially fewer and smaller foci were observed in mice without CM, and hypoxia seemed to be confined to neuronal cell somas. PARP-1-deficient mice were not protected against CM, which argues against a role for cytopathic hypoxia. Erythropoietin therapy reversed the development of CM and substantially reduced the degree of neural hypoxia. These findings demonstrate cerebral hypoxia in malaria, strongly associated with cerebral dysfunction and a possible target for adjunctive therapy.

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Expression of Hemoglobin in Rodent Neurons

Cited by 132 publications

References 39 publications

Protective effects of maternal nutritional supplementation with lactoferrin on growth and brain metabolism

Protective effects of maternal nutritional supplementation with lactoferrin on growth and brain metabolism

Evolutionary and Functional Properties of a Two-Locus β-Globin Polymorphism in Indian House Mice

CNS Hypoxia Is More Pronounced in Murine Cerebral than Noncerebral Malaria and Is Reversed by Erythropoietin

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