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PubMed2002

Differential effects of 19-nor-1,25-dihydroxyvitamin D(2) and 1,25-dihydroxyvitamin D(3) on intestinal calcium and phosphate transport.

19-Nor-1,25-dihydroxyvitamin D(2) (19-norD(2)) a less calcemic and phosphatemic analog of 1,25-dihydroxyvitamin D (1,25[OH](2)D(3)), is approved for the treatment of secondary hyperparathyroidism in patients with kidney failure. We have previously demonstrated that 19-norD(2) is less active than 1,25(OH)(2)D(3) in stimulating bone resorption. In this study, we compared the potencies of 19-norD(2) and 1,25(OH)(2)D(3) in stimulating net calcium and phosphate absorption in the intestine. Mineral balance was assessed in normal rats during the last 4 days of a 14-day treatment with various daily doses of 19-norD(2) or 1,25(OH)(2)D(3). Calcium absorption increased from 16.5% +/- 7.8% in vehicle-treated rats to 27.5% +/- 7.2% in rats given 10 ng/day 1,25(OH)(2)D(3) and to 21.6% +/- 3.9%, 26.2% +/- 5.5%, and 27.4% +/- 5.1% in rats treated with 10, 50, and 100 ng/day 19-norD(2), respectively. Thus comparable stimulation of calcium transport was attained with 10 ng 1,25(OH)(2)D(3) and 100 ng 19-norD(2). Similar results were obtained for phosphate absorption, with an increase from 28.2% +/- 5.5% in vehicle-treated rats to 40.2% +/- 4.7% in rats given 10 ng/day 1,25(OH)(2)D(3) and to 32.9% +/- 2.2%, 36.2% +/- 4.5%, and 36.8% +/- 3.8% in rats given 10, 50, and 100 ng/day 19-norD(2), respectively. Vitamin D compounds are believed to increase calcium absorption by inducing a calcium channel (epithelial calcium transporter or calcium transporter-1 [CaT1]) on the luminal membrane, a calcium-binding protein (Calbindin D9k) in the cytosol, and a calcium pump (plasma membrane calcium adenosine triphosphatase-1 [PMCA1]) on the basolateral membrane. Northern-blot analysis of intestinal ribonucleic acid of vitamin D-deficient rats given seven daily injections of vehicle or 100 ng 1,25(OH)(2)D(3) or 19-norD(2) revealed that 19-norD(2) was less potent than 1,25(OH)(2)D(3) in stimulating expression of CaT1, Calbindin D9k and PMCA1. In summary, the reduced calcemic and phosphatemic activities of 19-norD(2) can be attributed to lower potency in stimulating intestinal calcium and phosphate absorption.

Animals↗
PubMed1989

Parvalbumin increases in the caudate putamen of rats with vitamin D hypervitaminosis.

The influence of chronic vitamin D3 application on the concentration of the four calcium-binding proteins parvalbumin, the 28-kDa calbindin-D, calmodulin, and S-100 was studied in various brain regions and in the kidney. Young rats were administered daily 20,000 international units of vitamin D3 per kg (body weight) over a period of 4 months. This chronic treatment resulted in a clinically mild hypervitaminosis that did not affect the content of calmodulin, the 28-kDa calbindin-D, and S-100. Also the concentration of parvalbumin in the cerebral cortex, hippocampus, and kidney remained unchanged. On the other hand, parvalbumin was increased about 50% in the caudate putamen of hypervitaminotic animals as compared to controls. Our results indicate that the metabolism of parvalbumin in the caudate putamen can be influenced by variations of the blood level of this steroid hormone.

Animals↗
PubMed1992

Chronic deafferentation in monkeys differentially affects nociceptive and nonnociceptive pathways distinguished by specific calcium-binding proteins and down-regulates gamma-aminobutyric acid type A receptors at thalamic levels.

Chronic deafferentation of skin and peripheral tissues is associated with plasticity of representational maps in cerebral cortex and with perturbations of sensory experience that include severe "central" pain. This study shows that in normal monkeys the nonnociceptive, lemniscal component of the somatosensory pathways at spinal, brainstem, and thalamic levels is distinguished by cells and fibers immunoreactive for the calcium-binding protein parvalbumin, whereas cells of the nociceptive component at these levels are distinguished by immunoreactivity for 28-kDa calbindin. Long-term dorsal rhizotomies in monkeys lead to transneuronal degeneration of parvalbumin cells at brainstem and thalamic sites accompanied in the thalamus by a down-regulation of gamma-aminobutyric acid type A receptors and an apparent increase in activity of calbindin cells preferentially innervated by central pain pathways. Release from inhibition and imbalance in patterns of somatosensory inputs from thalamus to cerebral cortex may constitute subcortical mechanisms for inducing changes in representational maps and perturbations of sensory perception, including central pain.

Afferent Pathways↗
PubMed1995

The effect of protein concentration on ion binding.

The concentration of protein in a solution has been found to have a significant effect on ion binding affinity. It is well known that an increase in ionic strength of the solvent medium by addition of salt modulates the ion-binding affinity of a charged protein due to electrostatic screening. In recent Monte Carlo simulations, a similar screening has been detected to arise from an increase in the concentration of the protein itself. Experimental results are presented here that verify the theoretical predictions; high concentrations of the negatively charged proteins calbindin D9k and calmodulin are found to reduce their affinity for divalent cations. The Ca(2+)-binding constant of the C-terminal site in the Asn-56 --> Ala mutant of calbindin D9k has been measured at seven different protein concentrations ranging from 27 microM to 7.35 mM by using 1H NMR. A 94% reduction in affinity is observed when going from the lowest to the highest protein concentration. For calmodulin, we have measured the average Mg(2+)-binding constant of sites I and II at 0.325, 1.08, and 3.25 mM protein and find a 13-fold difference between the two extremes. Monte Carlo calculations have been performed for the two cases described above to provide a direct comparison of the experimental and simulated effects of protein concentration on metal ion affinities. The overall agreement between theory and experiment is good. The results have important implications for all biological systems involving interactions between charged species.

Alanine↗
PubMed1996

Suppression of trkB expression by antisense oligonucleotides alters a neuronal phenotype in the rod pathway of the developing rat retina.

trkB is the high-affinity receptor for brain-derived neurotrophic factor (BDNF), a trophic molecule with demonstrated effects on the survival and differentiation of a wide variety of neuronal populations. In the mammalian retina, trkB is localized to both ganglion cells and numerous cells in the inner nuclear layer. Much information on the role of BDNF in neuronal development has been derived from the study of trkB- and BDNF-deficient mutant mice. This includes an attenuation of the numbers of cortical neurons immunopositive for the calcium-binding proteins, parvalbumin, and calbindin. Unfortunately, these mutant animals typically fail to survive for > 24-48 hr after birth. Since most retinal neuronal differentiation occurs postnatally, we have devised an alternative scheme to suppress the expression of trkB in the retina to examine the role of BDNF on the postnatal development of neurons of the inner retina. Neonatal rats were treated with intraocular injection of an antisense oligonucleotide (1-2 microliters of 10-100 microM solution) targeted to the trkB mRNA. Immunohistochemistry with a polyclonal antibody to trkB showed that the expression of trkB in retinal neurons was suppressed 48-72 hr following a single injection. Northern blot analysis demonstrated that antisense treatment had no effect on the level of trkB mRNA, even after multiple injections. This suggests an effect of trkB antisense treatment on protein translation, but not on RNA transcription. No alterations were observed in the thickness of retinal cellular or plexiform layers, suggesting that BDNF is not the sole survival factor for these neurons. There were, however, alterations in the patterns of immunostaining for parvalbumin, a marker for the narrow-field, bistratified AII amacrine cell-a central element of the rod (scotopic) pathway. This was evidenced by a decrease in both the number of immunostained somata (> 50%) and in the intensity of immunolabeling. However, the immunostaining pattern of calbindin was not affected. These studies suggest that the ligands for trkB have specific effects on the neurochemical phenotypic expression of inner retinal neurons and in the development of a well-defined retinal circuit.

Animals↗
PubMed2003

Metabolism and requirements for calcium and phosphorus in the fast-growing chicken as affected by age.

Three series of experiments were conducted with fast-growing chickens in order: to evaluate the effects of dietary Ca and P on cholecalciferol metabolism and expression; to determine dietary Ca requirements; to determine dietary P requirements. The results of the first series confirmed previous results on the effects of dietary Ca and P on some variables of vitamin D metabolism and expression, Ca homeostasis and P metabolism in the young chicken (1- to 21-d-old), and extended them to older birds (22- to 43-d-old). The bone formation rate and the duodenal calbindin content were maintained at high levels until the age of 43 d. Dietary Ca or P restriction increased duodenal calbindin and decreased bone ash in both 22- and 43-d-old chickens, but the effect on bone ash was less pronounced in the 43-d-old birds than in the younger ones. These results suggest that: (a) the capabilities for adaptation to dietary Ca and P restriction remain high during the whole growing period; (b) the growing broilers express a high adaptive capability even when the diet contains the recommended Ca and P contents. The results of the second and third series of experiments suggest that: (c) unlike the Ca requirements of the 1- to 22-d-old chick, P requirements for growth and bone ash are similar, and are as high in the older chicks as in the younger ones (7.4-8.3 g P/kg or 4.8-5.7 g non-phytate P/kg diet); (d) although growth and bone ash in the 29- to 43-d-old chickens appear to be less sensitive to dietary Ca content, within a range close to the calculated P requirement, 10 g Ca/kg diet appears to be required for best tibia mineralization, and to a lesser extent for better growth at this age.

Aging↗
PubMed1989

Preliminary biochemical characterization of the stereocilia and cuticular plate of hair cells of the chick cochlea.

The sensory epithelium of the chick cochlea contains only two cell types, hair cells and supporting cells. We developed methods to rapidly dissect out the sensory epithelium and to prepare a detergent-extracted cytoskeleton. High salt treatment of the cytoskeleton leaves a "hair border", containing actin filament bundles of the stereocilia still attached to the cuticular plate. On SDS-PAGE stained with silver the intact epithelium is seen to contain a large number of bands, the most prominent of which are calbindin and actin. Detergent extraction solubilizes most of the proteins including calbindin. On immunoblots antibodies prepared against fimbrin from chicken intestinal epithelial cells cross react with the 57- and 65-kD bands present in the sensory epithelium and the cytoskeleton. It is probable that the 57-kD is a proteolytic fragment of the 65-kD protein. Preparations of stereocilia attached to the overlying tectorial membrane contain the 57- and 65-kD bands. A 400-kD band is present in the cuticular plate. By immunofluorescence, fimbrin is detected in stereocilia but not in the hair borders after salt extraction. The prominent 125 A transverse stripping pattern characteristic of the actin cross-bridges in a bundle is also absent in hair borders suggesting fimbrin as the component that gives rise to the transverse stripes. Because the actin filaments in the stereocilia of hair borders still remain as compact bundles, albeit very disordered, there must be an additional uncharacterized protein besides fimbrin that cross-links the actin filaments together.

Animals↗
PubMed2005

Relationship of prefrontal connections to inhibitory systems in superior temporal areas in the rhesus monkey.

The prefrontal cortex selects relevant signals and suppresses irrelevant signals in behavior, as exemplified by its functional interaction with superior temporal cortices. We addressed the structural basis of this process by investigating quantitatively the relationship of prefrontal pathways to inhibitory interneurons in superior temporal cortices. Pathways were labeled with neural tracers, and two neurochemical classes of inhibitory interneurons were labeled with parvalbumin (PV) and calbindin (CB), which differ in mode of inhibitory control. Both markers varied significantly and systematically across superior temporal areas. Calbindin neurons were more prevalent than PV neurons, with the highest densities found in posterior high-order auditory association cortices. Axons from anterior lateral, medial prefrontal and orbitofrontal areas terminated in the anterior half of the superior temporal gyrus, targeting mostly the superficial layers (I to upper III), where CB neurons predominated. Reciprocal projection neurons were intermingled with PV neurons, and emanated mostly from the deep part of layer III and to a lesser extent from layers V-VI, in proportions matching the laminar density of inhibitory interneurons. In marked contrast, prefrontal connections in temporal polar cortex were found mostly in the deep layers, showing mismatch with the predominant upper laminar distribution of interneurons. Differences in the relationship of connections to inhibitory neurons probably affect the dynamics in distinct superior temporal cortices. These findings may help explain the reduced efficacy of inhibitory control in superior temporal areas after prefrontal cortical damage.

Animals↗
PubMed1995

Dietary calcium levels and treatment interval determine the effects of lead ingestion on plasma 1,25-dihydroxyvitamin D concentration in chicks.

The combined effects of dietary calcium level and lead level on several indices of vitamin D endocrine function were examined in young, growing chicks. Day-old animals fed a nutritionally adequate diet for 2 wk were fed diets either adequate (1.2%) or low (0.1%) in calcium, and containing 0, 0.2 or 0.8% lead for an additional 1 or 2 wk. In the calcium-adequate group, lead ingestion significantly elevated intestinal calbindin-D28k protein and mRNA levels as well as plasma 1,25-dihydroxyvitamin D concentration compared with the control animals fed a lead-free diet. The effect was apparent after 1 wk of treatment and continued through wk 2. In the calcium-deficient group, the early (1 wk) increases in plasma 1,25-dihydroxyvitamin D and calbindin-D28k protein and mRNA were significantly reversed by lead ingestion over the 2-wk trial period in a dose-dependent fashion. In these circumstances, vitamin D endocrine function is severely compromised. Therefore, lead ingestion may result in either enhanced or diminished circulating 1,25-dihydroxyvitamin D concentrations and ensuing intestinal responses, depending of dietary calcium level and the duration of lead intake. These results provide possible explanations for several apparently conflicting sets of observations regarding lead-calcium interactions.

Animals↗
PubMed1994

CaBP9K levels during the luteal and follicular phases of the estrous cycle in the bovine uterus.

The expression of calbindin-D9K (CaBP9K) and calbindin-D28K (CaBP28K) genes in the reproductive system is well established for rodent and avian species, but not for domestic livestock. This investigation expanded the study of these proteins to include the bovine uterus and examined the levels of CaBP9K and CaBP9K mRNA in the nonpregnant bovine uterus during the estrous cycle. Immunohistochemical studies revealed that CaBP9K was present in all uterine glandular and luminal epithelial cells. In contrast, the closely related calcium binding protein CaBP28K was present in only one to two glandular cells in the samples examined. Neither protein was localized in the myometrium or in the stromal cells of the endometrium. RIA and dot blot hybridization were used to quantify the amount of CaBP9K and CaBP9K mRNA. The levels of both the protein and its mRNA were threefold higher during the luteal phase than during the follicular phase. RIA was also used to determine bovine uterine levels of 17 beta-estradiol and progesterone. Progesterone levels were higher during the luteal phase than during the follicular phase, while 17 beta-estradiol levels were higher during the follicular phase. This investigation represents the first characterization of CaBP9K gene expression in the bovine uterus. It demonstrated that the expression of CaBP9K and CaBP9K mRNA was greatest during the progesterone-dominated luteal phase of the bovine estrous cycle. These results indicated that CaBP9K may be involved in uterine glandular function during the luteal phase.

Animals↗
PubMed2002

Tolerance of horizontal cells to excitotoxicity in the developing FVB/N mouse retina.

We investigated the effect of L-glutamate on horizontal cell growth after postnatal photoreceptor degeneration in the developing FVB/N mouse retina, using immunocytochemistry with antisera against calbindin D-28 K (calbindin) or neurofilament 200 NE14. The numbers of horizontal cells and amount of axonal arborization in the outer plexiform layer were unchanged in FVB/N mice injected with L-glutamate. Instead, more numerous processes emerging from horizontal cells descended into the inner plexiform layer (IPL) and formed a loose network in stratum 1. Our results clearly demonstrate that horizontal cells are resistant to excitotoxicity by excessive glutamate, and that sprouting of horizontal cell axons into the IPL is potentiated by excessive glutamate in FVB/N mice as they mature.

Animals↗
PubMed1993

Neuronal changes in the cerebral cortex of the rat following alcohol treatment and thiamin deficiency.

The contribution of thiamin deficiency to the pathology of alcohol-related brain damage is still unclear. This study used a model of prolonged alcohol abuse in which animals were subjected to a brief period of mild thiamin deficiency. The episode of thiamin deficiency was early (after 4 weeks), in the middle (after 15 weeks) or late (after 26 weeks) in their 28 week alcohol treatment period. A control group of animals fed no alcohol and maintained on a thiamin-replete diet was used for comparison. The brains were removed and sectioned in the coronal plane at 50 microns intervals. Successive serial sections were stained with cresyl violet for Niss1 substance and immunohistochemically with antibodies to the calcium-binding proteins parvalbumin and calbindin. These calcium-binding proteins identify the majority of GABA-containing neurons in the cerebral cortex. The number of cells in the Fr1 region of the cerebral cortex was quantitated. A significant loss of Niss1-stained neurons was identified from the early group, while a loss of parvalbumin-immunoreactive neurons was seen in the early and middle groups. No loss of neurons was identified from the late group. In addition, no loss of calbindin-immunoreactive neurons was seen. This study represents the first report of cortical neuronal loss in an animal model of alcohol abuse and thiamin deficiency. Moreover, the results imply that thiamin deficiency is integrally involved in the pathogenesis of alcohol-related cortical neuronal loss.

Alcoholism↗
PubMed2004

A united residue force-field for calcium-protein interactions.

United-residue potentials are derived for interactions of the calcium cation with polypeptide chains in energy-based prediction of protein structure with a united-residue (UNRES) force-field. Specific potentials were derived for the interaction of the calcium cation with the Asp, Glu, Asn, and Gln side chains and the peptide group. The analytical expressions for the interaction energies for each of these amino acids were obtained by averaging the electrostatic interaction energy, expressed by a multipole series over the dihedral angles not considered in the united-residue model, that is, the side-chain dihedral angles chi and the dihedral angles lambda for the rotation of peptide groups about the C(alpha)...C(alpha) virtual-bond axes. For the side-chains that do not interact favorably with calcium, simple excluded-volume potentials were introduced. The parameters of the potentials were obtained from ab initio quantum mechanical calculations of model systems at the Restricted Hartree-Fock (RHF) level with the 6-31G(d,p) basis set. The energy surfaces of pairs consisting of Ca(2+)-acetate, Ca(2+)-propionate, Ca(2+)-acetamide, Ca(2+)-propionamide, and Ca(2+)-N-methylacetamide systems (modeling the Ca(2+)-Asp(-), Ca(2+)-Glu(-), Ca(2+)-Asn, Ca(2+)-Gln, and Ca(2+)-peptide group interactions) at different distances and orientations were calculated. For each pair, the restricted free energy (RFE) surfaces were calculated by numerical integration over the degrees of freedom lost when switching from the all-atom model to the united-residue model. Finally, the analytical expressions for each pair were fitted to the RFE surfaces. This force-field was able to distinguish the EF-hand motif from all potential binding sites in the crystal structures of bovine alpha-lactalbumin, whiting parvalbumin, calbindin D9K, and apo-calbindin D9K.

Animals↗
PubMed2002

The EF-hand domain: a globally cooperative structural unit.

EF-hand Ca(2+)-binding proteins participate in both modulation of Ca(2+) signals and direct transduction of the ionic signal into downstream biochemical events. The range of biochemical functions of these proteins is correlated with differences in the way in which they respond to the binding of Ca(2+). The EF-hand domains of calbindin D(9k) and calmodulin are homologous, yet they respond to the binding of calcium ions in a drastically different manner. A series of comparative analyses of their structures enabled the development of hypotheses about which residues in these proteins control the calcium-induced changes in conformation. To test our understanding of the relationship between protein sequence and structure, we specifically designed the F36G mutation of the EF-hand protein calbindin D(9k) to alter the packing of helices I and II in the apoprotein. The three-dimensional structure of apo F36G was determined in solution by nuclear magnetic resonance spectroscopy and showed that the design was successful. Surprisingly, significant structural perturbations also were found to extend far from the site of mutation. The observation of such long-range effects provides clear evidence that four-helix EF-hand domains should be treated as a single globally cooperative unit. A hypothetical mechanism for how the long-range effects are transmitted is described. Our results support the concept of energetic and structural coupling of the key residues that are crucial for a protein's fold and function.

Binding Sites↗
PubMed2004

Characterization of subpopulations of neurons producing melanin-concentrating hormone in the rat ventral diencephalon.

Neurons producing melanin-concentrating hormone (MCH) are involved in a large array of functions. Some of these functions may be mediated by specific subpopulations. One such subpopulation was characterized by the expression of the neurokinin 3 receptor and the 'cocaine- and amphetamine-regulated transcript' (CART) peptide, while another expresses neither one of these two molecules. MCH+/CART+ axons were traced throughout the brain and showed a strikingly different pattern of distribution than that of MCH+/CART- axons. Particularly, many MCH+/CART+ axons are observed in the telencephalon, while MCH+/CART- projections are mostly directed toward the brainstem. Calbindin, a protein involved in calcium homeostasis, has been largely used in many structures of the brain for the identification of neuronal phenotypes. However, few MCH neurons were labeled for this protein. On the other hand, neurons producing the peptides hypocretins (Hcrt), and codistributed with the MCH neurons, were all labeled for calbindin. Thus, at least two subpopulations of MCH neurons can be distinguished on the basis of neuronal phenotypes and connections. These neurons may be involved in distinct circuitry and in distinct functions.

Animals↗
PubMed2005

Coordinated control of renal Ca(2+) transport proteins by parathyroid hormone.

BACKGROUND: The kidney is one of the affected organs involved in the clinical symptoms of parathyroid hormone (PTH)-related disorders, like primary hyperparathyroidism and familial hypocalciuric hypercalcemia. The molecular mechanism(s) underlying alterations in renal Ca(2+) handling in these disorders is poorly understood. METHODS: Parathyroidectomized and PTH-supplemented rats and mice infused with the calcimimetic compound NPS R-467 were used to study the in vivo effect of PTH on the expression of renal transcellular Ca(2+) transport proteins, including the epithelial Ca(2+) channel transient receptor potential, vanilloid, member 5 (TRPV5), calbindins, and the Na(+)/Ca(2+)-exchanger (NCX1). In addition, the effect of PTH on transepithelial Ca(2+) transport in rabbit connecting tubule/cortical collecting duct (CNT/CCD) primary cultures was determined. RESULTS: Decreased PTH levels in parathyroidectomized rats or NPS R-467-infused mice, resulted in reduced expression of these proteins, which is consistent with diminished Ca(2+) reabsorption, causing the development of the observed hypocalcemia. PTH supplementation of parathyroidectomized rats restored the expression of the renal Ca(2+) transport machinery and serum Ca(2+) levels, independent of serum 1,25-dihydroxyvitamin D(3) levels and renal vitamin D or Ca(2+)-sensing receptor mRNA abundance. Inhibition of the PTH-stimulated transepithelial Ca(2+) transport by the TRPV5-specific inhibitor ruthenium red reduced the PTH-stimulated expression of calbindin-D(28K) and NCX1 in rabbit CNT/CCD primary cultures. CONCLUSION: PTH stimulates renal Ca(2+) reabsorption through the coordinated expression of renal transcellular Ca(2+) transport proteins. Moreover, the PTH-induced stimulation is enhanced by the magnitude of the Ca(2+) influx through the gatekeeper TRPV5, which in turn facilitates the expression of the downstream Ca(2+) transport proteins. Therefore, the renal transcellular Ca(2+) transport proteins, including TRPV5, could contribute to the pathogenesis of PTH-related disorders.

Aniline Compounds↗
PubMed2005

Quantitative neuropathologic correlates of changes in ratio of N-acetylaspartate to creatine in macaque brain.

PURPOSE: To elucidate the neuropathologic basis of transient changes in the ratio of N-acetylaspartate (NAA) to creatine (Cr) in the primate brain by using a simian immunodeficiency virus (SIV)-infected macaque model of the neurologic manifestation of acquired immune deficiency syndrome. MATERIALS AND METHODS: This study was approved by the Massachusetts General Hospital Subcommittee on Research and Animal Care and the Institutional Animal Care and Use Committee of Harvard University. Rhesus macaques infected with SIV were evaluated during the 1st month of infection. A total of 11 animals were studied, including four control animals, three animals sacrificed 12 days after infection, three animals sacrificed 14 days after infection, and one animal sacrificed 28 days after infection. All animals underwent in vivo proton ((1)H) magnetic resonance (MR) spectroscopy, and postmortem frontal lobe tissue was investigated by using high-spectral-resolution (1)H MR spectroscopy of brain extracts. In addition, quantitative neuropathologic analyses were performed. Stereologic analysis was performed to determine neuronal counts, and immunohistochemical analysis was performed to analyze three neuronal markers: synaptophysin, microtubule-associated protein 2 (MAP2), and calbindin. Analysis of variance (ANOVA) was used to determine substantial changes in neuropathologic and MR spectroscopic markers. Spearman rank correlations were calculated between plasma viral load and neuropathologic and spectroscopic markers. RESULTS: During acute infection with SIV, the macaque brain exhibited significant changes in NAA/Cr (P < .02, ANOVA) and synaptophysin (P < .013, ANOVA). There was no significant change in the concentration of Cr. No significant changes were found in neuronal counts or other immunohistochemical neuronal markers. With the Spearman rank test, a significant direct correlation was detected between synaptophysin and ex vivo NAA/Cr (r(s) = 0.72, P < .013). No correlation between NAA/Cr and neuronal counts, calbindin, or MAP2 was found. CONCLUSION: NAA/Cr is a sensitive marker of neuronal injury, not necessarily neuronal loss, and best correlates with synaptophysin, a marker of synaptodendritic dysfunction.

Animals↗
PubMed2002

Calcitropic gene expression suggests a role for the intraplacental yolk sac in maternal-fetal calcium exchange.

The expression of calcitropic genes and proteins was localized within murine placenta during late gestation (the time frame of active calcium transfer) with an analysis of several gene-deletion mouse models by immunohistochemistry and in situ hybridization. Parathyroid hormone-related protein (PTHrP), the PTH/PTHrP receptor, calcium receptor, calbindin-D(9k), Ca(2+)-ATPase, and vitamin D receptor were all highly expressed in a localized structure of the murine placenta, the intraplacental yolk sac, compared with trophoblasts. In the PTHrP gene-deleted or Pthrp-null placenta in which placental calcium transfer is decreased, calbindin-D(9k) expression was downregulated in the intraplacental yolk sac but not in the trophoblasts. These observations indicated that the intraplacental yolk sac contains calcium transfer and calcium-sensing capability and that it is a probable route of maternal-fetal calcium exchange in the mouse.

Animals↗