PubMed Health⌕ Search

Biomedical subjects

S R Hansson

Publications and source records attributed to S R Hansson.

15 recordsLinked to original sources
PubMed2007

Increased cystatin C expression in the pre-eclamptic placenta.

Trophoblast invasion is regulated by proteinases and their inhibitors. Cystatin C inhibits cysteine proteinases. The serum concentration of cystatin C is increased in late pregnancy and pre-eclampsia. We aimed to investigate whether the expression of cystatin C is increased in the pre-eclamptic placenta and to investigate the expression pattern of cystatin C mRNA and protein in placental tissue. Tissue samples from the central part of the placenta from 13 normal and 22 pre-eclamptic pregnancies were included. We used real-time polymerase chain reaction (RT-PCR) and in situ hybridization for mRNA expression analysis and immunohistochemistry and Western blotting for protein expression analysis. RT-PCR showed a significantly higher expression of cystatin C mRNA in pre-eclampsia than in normal pregnancy, with the highest expression in cases with severe pre-eclampsia. In situ hybridization revealed a distinct pattern of high expression in the extravillous trophoblast cells of the basal plate and low expression in the syncytiotrophoblast covering villi. The cystatin C protein distribution matched the mRNA expression pattern. Western blot analysis revealed an increased protein expression in cases with severe pre-eclampsia and confirmed the presence of cystatin C in amniotic fluid samples. The high expression of cystatin C mRNA in the extravillous trophoblast cells of the basal plate suggests a role for cystatin C in the regulation of proteases in placentation. Placental expression and secretion of cystatin C could contribute to the elevated maternal plasma levels seen in pre-eclampsia.

Adult↗
PubMed2006

Gene expression profiling of human placentas from preeclamptic and normotensive pregnancies.

The aim of this study was to investigate patterns of gene expression in placental samples from patients with preeclampsia (PE), persistent bilateral uterine artery notching (without PE), and normal controls. This study included placental tissue from nine women with PE, seven with uncomplicated pregnancies and five with bilateral uterine artery notching in Doppler velocimetry tracings. Human cDNA microarrays with 6500 transcripts/genes were used and the results verified with real-time PCR and in-situ hybridization. Multidimensional scaling method and random permutation technique demonstrated significant differences among the three groups examined. Within the 6.5K arrays, 6198 elements were unique cDNA clones representing 5952 unique UniGenes and 5695 unique LocusLinks. Multidimensional scaling plots showed 5000 genes that met our quality criteria; among these, 366 genes were significantly different in at least one comparison. Differences in three genes of interest were confirmed with real-time PCR and in-situ hybridization; acid phosphatase 5 was shown to be overexpressed in PE samples and calmodulin 2 and v-rel reticuloendotheliosis viral oncogene homolog A (RELA) were downregulated in PE and uterine artery notch placentas. In conclusion downregulation of RELA and calmodulin 2 might represent an attempt by the placenta to compensate for elevations in intracellular calcium, possibly caused by hypoxia and/or apoptosis, in both pregnancies with uterine artery notching and preeclampsia.

Adult↗
PubMed2004

Differential localization and expression of urokinase plasminogen activator (uPA), its receptor (uPAR), and its inhibitor (PAI-1) mRNA and protein in endometrial tissue during the menstrual cycle.

Normal endometrium is a highly dynamic tissue, which responds to ovarian steroids with cyclic proliferation, differentiation (secretion), and degradation (menstruation). The urokinase plasminogen activator (uPA)-dependent proteolytic cascade as well as ligand activation of the uPA receptor (uPAR) is critically involved in physiological as well as pathophysiological aspects of tissue expansion and remodelling. Cyclic variation and distribution of uPA, uPAR and plasminogen activator inhibitor 1 (PAI-1) mRNA were examined by in situ hybridization, real-time PCR and northern blot in normal endometrium. Their corresponding proteins were localized with immunohistochemistry. uPA mRNA is exclusively expressed by stromal cells, whereas uPA protein is present in both epithelial and stromal cells. Immunostaining for uPA protein is reduced or undetectable at midcycle, thus coinciding with peak concentration of uPA in the uterine fluid. uPAR mRNA is expressed by epithelial cells in the proliferative phase and by stromal cells in the secretory phase. However, epithelial cells stain for uPAR protein throughout the cycle, suggesting that uPAR may detach from stromal cells and then bind to epithelial cells in the secretory phase. PAI-1 mRNA is located in vessel walls. The late secretory phase has greatly increased expression of all three mRNA and their proteins, mainly in pre-decidual cells in the superficial stroma. Discordant localization of the mRNA and proteins suggest that uPA is produced by stromal cells, released and bound to epithelial cells in both the proliferative and secretory phases, whereas uPAR is released from the stroma and bound to epithelial cells in the secretory phase. Also, the present data together with earlier reports suggest that uPA is released from the epithelial cells to the uterine fluid.

Endometrium↗
PubMed2004

Norepinephrine transporter (NET), serotonin transporter (SERT), vesicular monoamine transporter (VMAT2) and organic cation transporters (OCT1, 2 and EMT) in human placenta from pre-eclamptic and normotensive pregnancies.

Pre-eclampsia is one of the most common causes of perinatal and maternal morbidity and mortality. High blood pressure and proteinuria are important clinical signs of pre-eclampsia. Sympathetic overactivity and elevated level of circulating vaso active substances, such as monoamines has been shown. Extracellular concentrations of monoamines are normally kept low by specific transporter proteins of which many are expressed in the placenta. In this study we used in situ hybridization and real-time PCR to study the gene expression of monoamine transporters, such as NET, SERT, VMAT2, EMT and OCT1/2, in normal as well as in pre-eclamptic placentae. We demonstrated high expression of NET mRNA in the trophoblast cells of the anchoring villi and a lower expression intensity in the chorionic villi. SERT mRNA was mainly detected in chorionic villi. VMAT2 mRNA was not detected in the central part of the placenta but was present in the spiral arteries of placenta bed biopsies, in cytokeratin positive cells. EMT mRNA was mainly detected in the intra lobular septa and together with OCT1 and OCT2 mRNAs also expressed in scattered cells of placental vessel adventitias. Moreover, quantitative analysis showed a significant lower expression of NET and EMT mRNAs in pre-eclamptic placentae as compared to the control group. A defective gene expression or function of these monoamines transporters might explain the elevated concentrations of monoamines in pre-eclamptic patients. Monoamine transporters may serve as a protective mechanism preventing vasoconstriction in the placental vascular bed and thereby securing a stable blood flow to the fetus.

Adult↗
PubMed2001

Dedifferentiation of serous ovarian cancer from cystic to solid tumors is associated with increased expression of mRNA for urokinase plasminogen activator (uPA), its receptor (uPAR) and its inhibitor (PAI-1).

The plasminogen activating system is involved in tumor growth and metastasis by degradation of extracellular matrix, and modulation of cell adhesion and migration. Benign and well-differentiated malignant ovarian tumors present as cystic lesions with preserved glandular morphology, whereas poorly differentiated tumors and metastases are solid with characteristic absence of glandular morphology. We analyzed the mRNAs for urokinase plasminogen activator (uPA), its receptor (uPAR), and inhibitor (PAI-1) in serous ovarian tumors by in situ hybridization and by densitometric scanning of Northern blots prepared from tissue extracts. The mRNA expressing cells in the in situ hybridization sections were evaluated and counted by two different observers. The number of mRNA expressing cells for uPA, uPAR and PAI-1 were all significantly increased in solid as compared with cystic malignant tumors. The increased expression of all three mRNA species was mainly located in the stroma of poorly differentiated tumors and metastases. Apart from being expressed in the stroma of these tumors, uPAR mRNA was also expressed by tumor cells located along the stromal/epithelial boarder. In addition, the tumor tissue content of uPA, uPAR and PAI-1 mRNAs as measured by Northern blots were higher in the solid as compared with the cystic tumors. Increased expression of uPA, uPAR and PAI-1 genes in the solid tumors suggest a correlation with a more aggressive phenotype.

Blotting, Northern↗
PubMed2000

Transient expression of a functional serotonin transporter in Merkel cells during late gestation and early postnatal rat development.

We and others have previously identified serotonin transporter mRNA throughout the trigeminal system in the whisker region, trigeminal ganglion, trigeminal nucleus and thalamic relay stations. In order to further implicate a role for the serotonin transporter in this sensory system, we have now characterized serotonin transporter gene expression and function in primary cultures from the rat snout, at several stages of gestation. In this study, we have demonstrated a transient expression of serotonin transporter mRNA in quinacrine-positive Merkel cells between embryonic day 16 and postnatal day 5. Peak levels of mRNA occurred at embryonic day 20 and postnatal day 1. Merkel cells in culture exhibited a transient, antidepressant-sensitive [3H]-serotonin uptake, which was maximal at a time in culture corresponding to embryonic day 22 (day of birth). This transient uptake of serotonin suggests a role for this monoamine during a critical time period of the developing trigeminal sensory system. Regulation of extracellular serotonin levels by transporter activity may reflect the specific formation of the merkel cell-sensory neuron complex in an analogous mechanism by which serotonin modulates synaptogenesis in the central nervous system.

Aging↗
PubMed1999

Regulation of norepinephrine transporter and tyrosine hydroxylase mRNAs after kainic acid-induced seizures.

Noradrenergic locus coeruleus (LC) efferents to the forebrain suppress seizures in several models of epilepsy. Using in situ hybridization, we demonstrate that tyrosine hydroxylase (TH) and norepinephrine transporter (NET) but not vesicular monoamine transporter 2 (VMAT2) mRNA levels are transiently elevated in LC neurons following kainic acid-induced status epilepticus. These increases of TH and NET mRNAs and presumably of the proteins themselves might enhance synthesis and reuptake of NE postictally.

Animals↗
PubMed1999

Serotonin transporter messenger RNA expression in neural crest-derived structures and sensory pathways of the developing rat embryo.

A growing body of evidence suggests that serotonin plays an important role in the early development of both neural and non-neural tissues from vertebrate and invertebrate species. Serotonin is removed from the extracellular space by the cocaine- and antidepressant-sensitive serotonin transporter, thereby limiting its action on receptors. In situ hybridization histochemistry was used to delineate serotonin transporter messenger RNA expression during rat embryonic development. Serotonin transporter messenger RNA was widely expressed beginning prior to organogenesis and throughout the second half of gestation. Strikingly, serotonin transporter messenger RNA was detected in neural crest cells, some of which respond to serotonin in vitro, and neural crest-derived tissues, such as autonomic ganglia, tooth primordia, adrenal medulla, chondrocytes and neuroepithelial cells, in the skin, heart, intestine and lung. Within the peripheral sensory pathways, two major cells types were serotonin transporter messenger RNA-positive: (i) sensory ganglionic neurons and (ii) neuroepithelial cells which serve as targets for the outgrowing sensory neurons. Several sensory organs (cochlear and retinal ganglionic cells, taste buds, whisker and hair follicles) contained serotonin transporter messenger RNA by late gestation. The expression of serotonin transporter messenger RNA throughout the sensory pathways from central nervous system relay stations [Hansson S. R. et al. (1997) Neuroscience 83, 1185-1201; Lebrand C. et al. (1996) Neuron 17, 823-835] to sensory nerves and target organs as shown in this study suggests that serotonin may regulate peripheral synaptogenesis, and thereby influence later processing of sensory stimuli. If the early detection of serotonin transporter messenger RNA in skin and gastrointestinal and airway epithelia correlates with protein activity, it may permit establishment of a serotonin concentration gradient across epithelia, either from serotonin in the amniotic fluid or from neuronal enteric serotonin, as a developmental cue. Our results demonstrating serotonin transporter messenger RNA in the craniofacial and cardiac areas identify this gene product as the transporter most likely responsible for the previously identified accumulation of serotonin in skin and tooth germ [Lauder J. M. and Zimmerman E. F. (1988) J. craniofac. Genet. devl Biol. 8, 265-276], and the fluoxetine-sensitive effects on craniofacial [Lauder J. M. et al. (1988) Development 102, 709-720; Shuey D. L. et al. (1992) Teratology 46, 367-378; Shuey D. L. et al. (1993) Anat. Embryol., Berlin 187, 75-85] and cardiac [Kirby M. L. and Waldo K. L. (1995) Circulation Res. 77, 211-215; Yavarone M. S. et al. (1993) Teratology 47, 573-584] malformations. Serotonin transporter messenger RNA was detected in several neural crest cell lineages and may be useful as an early marker for the sensory lineage in particular. The distribution of serotonin transporter messenger RNA in early development supports the hypothesis that serotonin may play a role in neural crest cell migration and differentiation [Lauder J. M. (1993) Trends Neurosci. 16, 233-240], and that the morphogenetic actions of serotonin may be regulated by transport. The striking pattern of serotonin transporter messenger RNA throughout developing sensory pathways suggests that serotonin may play a role in establishing patterns of connectivity critical to processing sensory stimuli. As a target for drugs, such as cocaine, amphetamine derivatives and antidepressants, expression of serotonin transporter during development may reflect critical periods of vulnerability for fetal drug exposure. The widespread distribution of serotonin transporter messenger RNA during ontogeny suggests a previously unappreciated role of serotonin in diverse physiological systems during embryonic development.

Animals↗
PubMed1998

Infraorbital nerve transection alters serotonin transporter expression in sensory pathways in early postnatal rat development.

The serotonin transporter MRNA has been found throughout the trigeminal sensory system late in gestation and during early postnatal development, a period known to be critical for maturation of the sensory circuitry. The purpose of the present study was to determine whether sensory denervation in newborn rat pups would alter either the density or pattern of expression of the 5-HT transporter (5-HTT) within the trigeminal system. We combined autoradiographic localization of 5-HT transporters and in situ hybridization techniques to visualize both the transporter protein and mRNA in thalamic sensory neurons and in the somatosensory cortex following unilateral infraorbital nerve transection at postnatal day 1. For comparative purposes, similar measurements were conducted in thalamic visual neurons as well as in the visual cortex. Lesion of the infraorbital nerve decreased the [3H]citalopram labelling of 5-HT transporters in the ventral basal and ventral medial areas of the thalamus contralateral to the lesion, while labelling of 5-HT transporters was decreased in both contralateral and ipsilateral sides of the lateral genicuate (visual thalamus). Citalopram labelling of 5-HT transporters was not significantly altered in somatosensory or in cingulate cortex, however a significant decrease was observed in the visual cortex. In contrast, there were no obvious changes in the intensity of the 5-HT mRNA hybridization signal in sensory or visual thalamic areas. Given that the serotonin transporter regulates extracellular concentrations of 5-HT, the present data suggest that altered peripheral innervation and thereby altered sensory inputs to the thalamus during fetal development can potentially influence 5-HT transporter densities and thus, may influence extracellular levels of 5-HT in thalamus and cortex during a critical period of synapse formation. In turn, modulation of 5-HT transporter levels may influence extracellular concentrations of 5-HT in thalamus and cortex during a critical period of synapse formation.

Animals↗
PubMed1998

Ontogeny of vesicular monoamine transporter mRNAs VMAT1 and VMAT2. II. Expression in neural crest derivatives and their target sites in the rat.

We used in situ hybridization histochemistry to study the expression of the two vesicular monoamine transporters (VMAT1 and VMAT2) during embryonic development in the rat. In the adult rat VMAT2 is present exclusively in neuronal tissues and VMAT1 is present in the adrenal medulla and in certain intestinal endocrine cells. We found that both transporter molecules are more widely expressed during development. We demonstrate a complete overlap of the two VMAT mRNAs in the sympathetic nervous system between E13 and E21 days. In addition, VMAT2 (and to some extent VMAT1) mRNA is expressed in ganglionic cells of the parasympathetic nervous system and in cranial ganglia (trigeminal, vestibular and spiral ganglia) between E12 and E21. The sensory neurons of the dorsal root ganglia, which are also neural crest derivatives, express VMAT2 mRNA (E11-E21), exclusively. Both VMAT mRNAs are found in the developing GI system, but in different cells. VMAT1 mRNA was detected in organs of the endocrine system (pituitary gland, adrenal gland, testis, seminal vesicle), some connective tissue cells, and the thymus. We observed expression of both VMAT mRNAs in two separate cell groups in the placenta (E8-E10). Based on their distribution during development we suggest that monoamines, released in a controlled fashion, might affect migration and differentiation of neural crest derivatives.

Adrenal Medulla↗
PubMed1998

Ontogeny of vesicular monoamine transporter mRNAs VMAT1 and VMAT2. I. The developing rat central nervous system.

We used in situ hybridization histochemistry to study the expression of the mRNA of the two vesicular monoamine transporters (VMAT1 and VMAT2) during embryonic and postnatal development of the central nervous system (CNS) in the rat. In the adult rat, VMAT2 mRNA is present exclusively in monoaminergic cell groups of the CNS and VMAT1 mRNA was reported to be present in the adrenal medulla and certain intestinal epithelial cells. In contrast to the above, the expression of VMAT1 mRNA has previously never been detected in the central nervous system. This study shows the first evidence that both transporter molecules are expressed in CNS during ontogenesis. We here demonstrate four main expression patterns detected during development: 1. VMAT2 mRNA expression in monoaminergic neurons of the brainstem beginning as early as embryonic day E13. 2. Expression of VMAT2 mRNA in all major sensory relay nuclei of central nervous system. 3. Co-expression of VMAT1 and VMAT2 mRNA in most limbic structures, basal ganglia, as well as in some hypothalamic nuclei. 4. Exclusive expression of VMAT1 mRNA in the neocortical subventricular zone, in the amygdala at early (E15-18) and late (P1-P28) timepoints, the granular cell layer of cerebellum, and in several brainstem motor nuclei. Based on their distribution during development we suggest that monoamines, released in a controlled fashion, might affect wiring of sensory and also motor circuits. VMAT1 mRNA expression may reflect a specific effect of monoamines in glial differentiation and cerebellar granule cell migration and/or differentiation.

Aging↗
PubMed1998

Localization and dynamic regulation of biogenic amine transporters in the mammalian central nervous system.

The monoamines, serotonin, dopamine, norepinephrine, epinephrine and histamine, play a critical role in the function of the hypothalamic-pituitary-adrenal axis and in the integration of information in sensory, limbic, and motor systems. The primary mechanism for termination of monoaminergic neurotransmission is through reuptake of released neurotransmitter by Na+, CI-dependent plasma membrane transporters. A second family of transporters packages monoamines into synaptic and secretory vesicles by exchange of protons. Identification of those cells which express these two families of neurotransmitter transporters is an initial step in understanding what adaptive strategies cells expressing monoamine transporters use to establish the appropriate level of transport activity and thus attain the appropriate efficiency of monoamine storage and clearance. The most recent advances in this field have yielded several surprises about their function, cellular and subcellular localization, and regulation, suggesting that these molecules are not static and most likely are the most important determinants of extracellular levels of monoamines. Here, information on the localization of mRNAs for these transporters in rodent and human brain is summarized along with immunohistochemical information at the light and electron microscopic levels. Regulation of transporters at the mRNA level by manipulation in rodents and differences in transporter site densities by tomographic techniques as an index of regulation in human disease and addictive states are also reviewed. These studies have highlighted the presence of monoamine neurotransmitter transporters in neurons but not in glia in situ. The norepinephrine transporter is present in all cells which are both tyrosine hydroxylase (TH)- and dopamine beta-hydroxylase-positive but not in those cells which are TH- and phenyl-N-methyltransferase-positive, suggesting that epinephrine cells may have their own, unique transporter. In most dopaminergic cells, dopamine transporter mRNA completely overlaps with TH mRNA-positive neurons. However, there are areas in which there is a lack of one to one correspondence. The serotonin transporter (5-HTT) mRNA is found in all raphe nuclei and in the hypothalamic dorsomedial nucleus where the 5-HTT mRNA is dramatically reduced following immobilization stress. The vesicular monoamine transporter 2 (VMAT2) is present in all monoaminergic neurons including epinephrine- and histamine-synthesizing cells. Immunohistochemistry demonstrates that the plasma membrane transporters are present along axons, soma, and dendrites. Subcellular localization of DAT by electron microscopy suggests that these transporters are not at the synaptic density but are confined to perisynaptic areas, implying that dopamine diffuses away from the synapse and that contribution of diffusion to dopamine signalling may vary between brain regions. Interestingly, the presence of VMAT2 in vesicles underlying dendrites, axons, and soma suggests that monoamines may be released at these cellular domains. An understanding of the regulation of transporter function may have important therapeutic consequences for neuroendocrine function in stress and psychiatric disorders.

Amino Acid Sequence↗
PubMed1998

Serotonin transporter messenger RNA in the developing rat brain: early expression in serotonergic neurons and transient expression in non-serotonergic neurons.

Serotonin has been shown to affect the development of the mammalian nervous system. The serotonin transporter is a major factor in regulating extracellular serotonin levels. Using in situ hybridization histochemistry the rat serotonin transporter messenger RNA was localized during embryogenesis, the first four weeks postnatally and adulthood. Three general classes of serotonin transporter messenger RNA expression patterns were observed: (i) early detection with continued expression through adult age, (ii) transient expression colocalized with vesicular monoamine transporter 2 messenger RNA but with no detectable tryptophan hydroxylase immunoreactivity, and (iii) transient expression in the apparent absence of both vesicular monoamine transporter 2 messenger RNA and tryptophan hydroxylase immunoreactivity. For example, hybridization for serotonin transporter messenger RNA was strong in serotonin cell body-containing areas beginning early in gestation, and remained intense through adulthood. Immunoreactivity for tryptophan hydroxylase, the rate-limiting enzyme in serotonin synthesis, was completely overlapping with the presence of serotonin transporter messenger RNA in raphe nuclei postnatally. Sensory relay systems including the ventrobasal nucleus (somatosensory), lateral and medial geniculate nuclei (visual and auditory, respectively) as well as trigeminal, cochlear and solitary nuclei were representative of the second class of observations. In general, the limbic system expressed serotonin transporter messenger RNA in the third pattern with various limbic structures differing in the timing of expression. Septum, olfactory areas and the developing hippocampus contained serotonin transporter messenger RNA early in the developing brain. Other regions such as cingulate and frontopolar cortex exhibited hybridization peri- and postnatally, respectively. Several hypothalamic nuclei and pituitary transiently expressed serotonin transporter messenger RNA either postnatally or perinatally, respectively. If the observed patterns correlate with functional protein expression, distinct classes of serotonin transporter messenger RNA expression may reflect different functional roles for the serotonin transporter and serotonin, itself. Since the serotonin transporter is a target for a number of addictive substances including cocaine and amphetamine derivatives as well as antidepressants, transient expression of the serotonin transporter might suggest a window of vulnerability of associated cells to fetal drug exposure. Re-uptake, storage and re-release from non-serotonergic neurons might serve as a feedback mechanism from target neurons to serotonergic neurons. Alternatively, the transient expression of serotonin transporter messenger RNA may reflect critical periods important for tight regulation of extracellular serotonin in several brain regions, and may indicate previously unappreciated roles for serotonin as a developmental cue.

Aging↗
PubMedDate not supplied

Dopaminergic characteristics of isolated parietal cells from rats.

Recently we have identified a dopamine-producing system in the gastric mucosa of rats. All the available morphological data suggest that parietal cells synthesize dopamine. In the present study we investigated the dopaminergic characteristics of isolated parietal cells by different methods. Mixed gastric mucosal cells were isolated and size-fractionated by elutriation. The proportion of neurons, parietal and endocrine cells in the fractions were determined by immunocytochemistry (ICC) using antibodies to neurofilament, proton pump and chromogranin A, respectively. No neurons were found in any of the cell preparations, while 56% parietal cell and 0.0% endocrine cell were achieved in the parietally enriched fraction. By Western blot, a tyrosine hydroxylase (TH, the rate-limiting enzyme of the catecholamine synthesis) immunoreactive protein species was demonstrated in isolated mucosal cells, comigrating with the TH immunoreactivity from PC12 cells. The TH immunoreactivity was colocalized to parietal cells by ICC. Dopamine transporter (DAT), a regulator of extracellular/intracellular dopamine balance in the nervous system, was also demonstrated in parietal cells. A significant amount of dopamine and DOPA were measured by HPLC (13.4 and 9.57 pg/10(6) cell, respectively) in parietally enriched cell fraction. Since this enriched cell fraction was virtually clear of both neurons and endocrine cells, demonstration of TH enzyme, DAT and dopamine in this fraction confirms that the parietal cell population might be a major source of dopamine in the rat stomach, supporting our previous results achieved using whole tissue samples.

Animals↗