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E Hansson

Publications and source records attributed to E Hansson.

At least 19 recordsLinked to original sources
PubMed2006

Corticosterone inhibits expression of the microglial glutamate transporter GLT-1 in vitro.

The present study investigates the effect of the glucocorticoid corticosterone on microglial glutamate transporters in vitro. Microglial cultures obtained from rat cerebral cortex were found to express the excitatory amino acid transporter GLT-1, but not GLAST, and this expression was increased by 1 ng/ml lipopolysaccharide after 12 h of stimulation. This increase has previously been shown to be mediated by tumor necrosis factor-alpha, a cytokine released by microglia during pathological conditions. Furthermore, lipopolysaccharide increased the microglial release of tumor necrosis factor-alpha and 1 microM corticosterone inhibited this effect. Corticosterone also inhibited the lipopolysaccharide-induced increase of the GLT-1 expression as well as the expression in non-activated cells. The effect of corticosterone on the GLT-1 expression was dose dependent and accompanied by similar effects on the microglial glutamate uptake capacity. Additionally, exogenous tumor necrosis factor-alpha was found to counteract the effect of corticosterone on microglial GLT-1 expression. The effect of corticosterone appeared to be glucocorticoid receptor specific since 10 microM of the glucocorticoid receptor antagonist mifepristone inhibited the effect. Thus, corticosterone decreased the microglial uptake of glutamate by decreasing the expression of glutamate transporters, probably due to the inhibited microglial tumor necrosis factor-alpha release. These results provide insights into the mechanisms behind microglial glutamate transporter expression during pathological conditions, and contribute to the debate about the beneficial or harmful effects of glucocorticoids.

Analysis of Variance↗
PubMed2001

Alpha 1-adrenergic modulation of metabotropic glutamate receptor-induced calcium oscillations and glutamate release in astrocytes.

Astrocytic responses to activation of metabotropic glutamate receptors group I (mGluRs I) and alpha(1)-adrenoreceptors in cultured cells have been assessed using spectral analyzes and calcium imaging. Concentration-dependent changes were observed after stimulation with the mGluR I agonist (S)-3,5-dihydroxyphenylglycine (DHPG). These responses changed from a regular low frequency signal with sharp peaks at 1 microm to a pronounced stage of irregularity at 10 microm. After stimulation with 100 microm the signal was again homogenous in shape and regularity but occurred at a higher frequency. In contrast, the spectral properties after stimulation with the alpha(1)-adrenoreceptor agonist phenylephrine, exhibited considerable variation for all investigated concentrations. DHPG-induced increases in [Ca(2+)](i) were also associated with astroglial glutamate release, whereas no release was observed after noradrenergic stimulation. Both DHPG-mediated calcium signaling and glutamate release were inhibited by preincubation with 10 or 100 microm phenylephrine. Collectively, the present investigation provides new information about the spatial-temporal characteristics of astroglial intracellular calcium responses and demonstrates distinct differences between noradrenergic and glutamatergic receptors regarding intracellular calcium signaling and coupling to glutamate release. The noradrenergic modulation of DHPG-induced responses indicates that intracellular astroglial processes can be regulated in a bi-directional feedback loop between closely connected astrocytes and neurons in the central nervous system.

Animals↗
PubMed2001

Prognostic utility of human complement factor H related protein test (the BTA stat Test).

The purpose of the study was to determine, in addition to well-known prognostic factors, histological grade, stage, tumour size and multiplicity, the correlation of BTA stat Test on disease free interval (DFI) on primary superficial bladder cancer. A total of 116 patients with newly diagnosed bladder cancer were evaluated in a prospective multicentre study. A voided urine sample was obtained prior to TURB and split for culture, cytology and BTA stat testing. Follow-up data for the patients were collected until the first recurrence or the last visit and the DFI was analysed by Kaplan-Meier method and Cox analysis. Ninety-seven of the 116 (83.6%) patients were eligible for analysis. The BTA stat Test was positive in 73 (75.3%) patients, whereas cytology detected 20 (20.6%) cases. The DFI was found to be shorter among patients with a positive BTA stat Test, and also among those with intermediate or high-grade tumours. The BTA stat Test result divided patients with grade 2 tumours into two prognostic groups, in that those testing positive had 68.6% risk of recurrence during the first year compared to 42.9% risk of those with a negative test result (P = 0.041). Although the effect of tumour size on DFI was notable, the difference did not reach statistical significance (P = 0.064). Number of tumours was not related to DFI, nor was the difference between different stage of tumour of significance. BTA stat Test is not only sensitive in detection of primary bladder cancer, but also might have some independent prognostic significance.

Adult↗
PubMed2001

Virulent Newcastle disease in Australia: molecular epidemiological analysis of viruses isolated prior to and during the outbreaks of 1998-2000.

Gene sequence analysis of fusion (F) gene cleavage motifs and haemagglutinin-neuraminidase (HN) carboxyl-terminal extension sequences was used to analyse Newcastle disease viruses (NDV) associated with virulent outbreaks of the disease which occurred in New South Wales, Australia in 1998-2000. PCR fragments were amplified directly from diseased tissue or allantoic fluids and sequence analyses used for phylogenetic comparisons between these viruses and Australian reference NDV. F and HN gene sequence comparison showed a strong relationship to sequences derived from endemic Australian NDV rather than those of overseas viruses or wild bird isolates. Prior to notification of the 1998 outbreak, an NDV was isolated from chickens suffering respiratory disease that appeared to be the progenitor virus from which the virulent virus originated. In turn, these viruses are closely related to two previously isolated 'ancestor' viruses that have the same unique HN extension sequence.

Amino Acid Sequence↗
PubMed2001

Activation of beta-adrenoceptors opens calcium-activated potassium channels in astroglial cells.

In the present study, effects of the alpha(2)- and beta-adrenoceptor agonists clonidine and isoproterenol on astrocytes in astroglial/neuronal cocultures from rat cerebral cortex were evaluated. The calcium- and potassium-sensitive dyes fura-2 and potassium-binding benzofuran isophtalate (PBFI) were used to study alterations in intracellular concentrations of calcium ([Ca(2+)](i)) and potassium ([K(+)](i)), respectively, while the perforated patch clamp technique was used to analyze transmembrane currents. Exposure to isoproterenol or clonidine elicited an immediate increase in [Ca(2+)](i) that was totally abolished in calcium-free extracellular media. Isoproterenol also decreased [K(+)](i), but clonidine did not. The reduction in [K(+)](i) was inhibited in Ca(2+)-free media. As evaluated with the perforated patch technique, isoproterenol (10(-6)-10(-4) M) induced a slowly developing and long lasting outward current that also was totally abolished in calcium-free buffer. This current was blocked by external tetraethylammonium (TEA, 10 mM) and charybdotoxin (ChTX, 10 nM), but was not affected by apamin (50 nM). The current-to-voltage (I-V) relationships for the isoproterenol-induced currents showed a markedly negative reversal potential, -96 mV+/-7, (mean+/-S.D., n=5). These results suggest that the stimulation of astroglial beta-adrenoceptors by isoproterenol opens calcium-activated potassium channels (K((Ca))). Preincubation with forskolin significantly increased the isoproterenol-induced currents compared with controls, indicating that the opening of astroglial K((Ca)) channels after beta-adrenergic stimulation not only depends on [Ca(2+)](i) but also synergistically involves the cAMP transduction system to which beta-adrenoceptors are known to be positively coupled.

Adrenergic alpha-2 Receptor Agonists↗
PubMed2001

Signaling and gene expression in the neuron-glia unit during brain function and dysfunction: Holger Hydén in memoriam.

Holger Hydén demonstrated almost 40 years ago that learning changes the base composition of nuclear RNA, i.e. induces an alteration in gene expression. An equally revolutionary observation at that time was that a base change occurred in both neurons and glia. From these findings, Holger Hydén concluded that establishment of memory is correlated with protein synthesis, and he demonstrated de novo synthesis of several high-molecular protein species after learning. Moreover, the protein, S-100, which is mainly found in glial cells, was increased during learning, and antibodies towards this protein inhibited memory consolidation. S-100 belongs to a family of Ca(2+)-binding proteins, and Holger Hydén at an early point realized the huge importance of Ca(2+) in brain function. He established that glial cells show more marked and earlier changes in RNA composition in Parkinson's disease than neurons. Holger Hydén also had the vision and courage to suggest that "mental diseases could as well be thought to depend upon a disturbance of processes in glia cells as in the nerve cells", and he showed that antidepressant drugs cause profound changes in glial RNA. The importance of Holger Hydén's findings and visions can only now be fully appreciated. His visionary concepts of the involvement of glia in neurological and mental illness, of learning being associated with changes in gene expression, and of the functional importance of Ca(2+)-binding proteins and Ca(2+) are presently being confirmed and expanded by others. This review briefly summarizes highlights of Holger Hydén's work in these areas, followed by a discussion of recent research, confirming his findings and expanding his visions. This includes strong evidence that glial dysfunction is involved in the development of Parkinson's disease, that drugs effective in mood disorders alter gene expression and exert profound effects on astrocytes, and that neuronal-astrocytic interactions in glutamate signaling, NO synthesis, Ca(2+) signaling, beta-adrenergic activity, second messenger production, protein kinase activities, and transcription factor phosphorylation control the highly programmed events that carry the memory trace through the initial, signal-mediated short-term and intermediate memory stages to protein synthesis-dependent long-term memory.

Animals↗
PubMed2001

Acute ethanol exposure induces [Ca2+]i transients, cell swelling and transformation of actin cytoskeleton in astroglial primary cultures.

Acute exposure to 100 mM isotonic ethanol (EtOH) increased intracellular Ca2+ concentration ([Ca2+]i), induced cell swelling, and transformed actin cytoskeleton in astroglial primary cultures from rat cerebral cortex. Fluorometric recordings of fluo-3AM- or fura-2AM-incubated astroglial cells revealed that EtOH induced [Ca2+]i transients in a small population of the cells. Cell swelling was estimated using a new method based on three-dimensional fluorescence imaging in conjunction with image analysis and graphic visualization techniques. The method provides detailed results concerning the reformation of structural shape and specific volume alterations, as well as total proportions between the different states. Astroglial cell swelling was registered and quantified in 7 of 39 cells chosen from 12 different coverslips. EtOH also induced reversible conformational changes in filamentous actin, appearing as increases in ring formations and a more dispersed appearance of the filaments. Filamentous actin was stained with Alexa phalloidin after incubation with EtOH for varied periods. The results presented here suggest that EtOH affects astrocytes in a way that could be of physiological relevance.

Actins↗
PubMed2001

Endothelin-1 decreases glutamate uptake in primary cultured rat astrocytes.

Endothelin-1 (ET-1) is a potent vasoconstrictor peptide that is also known to induce a wide spectrum of biological responses in nonvascular tissue. In this study, we found that ET-1 (100 nM) inhibited the glutamate uptake in cultured astrocytes expressing the glutamate/aspartate transporter (GLAST); astrocytes did not express the glutamate transporter-1 (GLT-1). The V(max) and the K(m) of the glutamate uptake were reduced by 57% and 47%, respectively. Application of the ET(A) and ET(B) receptor antagonists BQ-123 and BQ-788 partly inhibited the ET-1-evoked decrease in the glutamate uptake, whereas the nonspecific ET receptor antagonist bosentan completely inhibited this decrease. Incubation of the cultures with pertussis toxin abolished the effect of ET-1 on the uptake. The ET-1-induced decrease in the glutamate uptake was independent of extracellular free Ca(2+) concentration, whereas the intracellular Ca(2+) antagonists thapsigargin and 3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester abolished the effect of ET-1 on the glutamate uptake. Incubation with the protein kinase C (PKC) antagonist staurosporine, but not with the fatty acid-binding protein bovine serum albumin, prevented the ET-1-induced decrease in the glutamate uptake. These results suggest that ET-1 impairs the high-affinity glutamate uptake in cultured astrocytes through a G protein-coupled mechanism, involving PKC and changes in intracellular Ca(2+).

Amino Acid Sequence↗
PubMed2000

[The star-shaped cells. Astrocytes are involved in the pathogenesis and progress of neurological diseases].

Recently, knowledge about the role of astrocytes in the brain has increased substantially. As a result we have had to rethink old views regarding how the brain works at the cellular level. Neurons can no longer be regarded as the only cell types of functional significance. The picture instead appears to be far more complex, with an ongoing exchange of information between different cell types, and this interaction is suggested to be particularly important between neurons and astrocytes. Astrocytes express receptors for different classes of neurotransmitters, and have both voltage and receptor operated ion channels. Through active uptake and release of ions, neurotransmitters and water they control the brain interstitium. Intercellular communication via transfer of neuroactive substances through gap junctions makes it possible to coordinate different activities in large areas of the brain. Dysfunction of astrocytic physiology is thought to contribute to the pathogenesis and progress of various neurological disorders such as epilepsy, stroke and cerebral edema.

Astrocytes↗
PubMed2000

Differential expression of delta opioid receptors and mRNA in proliferating astrocytes during the cell cycle.

Previous immunohistochemical and radioligand binding studies have shown a cell cycle-dependent regulation of the delta opioid receptor (DOR). The relationship between DOR expression and mitosis in primary astroglial cultures of rat cerebral cortex was investigated in this study. The cultures were arrested during the G(1)/S transition or during mitosis. The DOR protein level increased twofold (P = 0.009) during mitosis and DOR mRNA level increased threefold (P = 0.002) during the G(1)/S transition compared to nonsynchronized cultures. DOR mRNA was also elevated (1.6-fold, P = 0.008) during the G(1)/S transition compared with mitotic cells. A premitotic increase in DOR mRNA suggests that elevated DOR protein levels during mitosis might be regulated during transcription.

Animals↗
PubMed2000

Astrocyte beta1-adrenergic receptor immunoreactivity and agonist induced increases in [Ca2+]i: differential results indicative of a modified membrane receptor.

Antibodies against the C-terminus of the beta1-adrenergic receptor were used for staining cultured astrocytes from the rat cerebral cortex. Immunoreactivity was found to be localized exclusively to an intracellular organelle structure similar to the Golgi complex, with no staining of the plasma membrane. The astrocytes stained positive with BODIPY CGP 12177, a FITC-conjugated beta-adrenergic receptor agonist, and this staining was blocked by the beta1-adrenergic antagonist atenolol, indicating that these receptors are expressed on the surface of the astrocytes. The presence of functional plasma membrane beta1-adrenergic receptors was further verified using microspectrofluorometry for measurements of intracellular calcium changes upon beta-adrenergic agonist stimulation. Intracellular immunoreactivity confined to the organelles was also found in astrocytes from mixed astroglial-neuronal cultures. In contrast, the neurons in these cultures showed a strong labeling of the cell bodies by the beta1-adrenergic receptor antibodies. Thus, the beta1-adrenergic receptor antibody, which stains the cell bodies of the neurons, recognizes the astroglial receptors only intracellularly, although functional beta1-adrenergic receptors are present on the astroglial surface. Taken together, these data suggest that the beta1-adrenergic receptors observed intracellularly might be processed on their passage to the surface to a modified form of the final plasma membrane receptor, which is not recognized by the antibodies.

Adrenergic alpha-Agonists↗
PubMed2000

[Astrocytes--anonymous cells in the brain, participating in neurasthenic symptoms].

During rehabilitation after brain damage due to stroke or trauma, or after meningitis, patients often suffer from mental fatigue and decreased capacity for concentration and learning. We hypothesize that one pathogenic cause of these symptoms could be a failure on the part of astroglia to remove glutamate and K+ from synaptic regions during glutamatergic transmission. As astroglial support of neuronal glutamate transmission has been shown to be of utmost importance, such an astroglial failing might lead to a decreased signal-to-noise ratio in glutamatergic neurotransmission, especially when the transmission is intense for a considerable time period. Three aspects of astroglial failing are focused upon: decreased capacity of the astroglial glutamate transporters, depolarization of the astroglial network, and uncoupling of the gap junction coupled astroglial network. It has been shown that several neuroactive substances, present within the nervous system even long after damage or infection, influence upon these three astroglial properties.

Animals↗
PubMed2000

5-Hydroxytryptamine2B receptors stimulate Ca2+ increases in cultured astrocytes from three different brain regions.

The expression of 5-hydroxytryptamine-2B (5-HT2B) receptor mRNA has recently been shown in cultured astrocytes. Here the expression of functional 5-HT2B receptors has been studied in cultured astrocytes from rat cerebral cortex, hippocampus, and brain stem. Fluo-3- and fura-2-based microspectrofluorometry was used for measuring changes in intracellular free calcium concentrations ([Ca2+]i). The 5-HT2B agonist alpha-methyl 5-HT (40 nM) produced rapid transient increases in [Ca2+]i in astrocytes from all three brain regions studied, and these responses were blocked by the selective 5-HT2B antagonist rauwolscine (1 microM). The specificity of the responses to alpha-methyl 5-HT was further demonstrated by the failure of 4-(4-fluorobenzoyl)-1-(4-phenylbutyl)-piperidine oxalate (1 microM), a specific 5-HT2A/5-HT2C antagonist, to block these responses. The 5-HT2B-induced increases in [Ca2+]i persisted in Ca2+-free buffer, indicating that the increase in [Ca2+]i results from mobilization of intracellular Ca2+ stores. The expression of 5-HT2B receptors on astroglial cells was further verified immunohistochemically and by Western blot analysis. These results provide evidence of the existence of 5-HT2B receptors on astrocytes in primary culture.

Animals↗
PubMed2000

The exceptionally large genome of Hendra virus: support for creation of a new genus within the family Paramyxoviridae.

An outbreak of acute respiratory disease in Hendra, a suburb of Brisbane, Australia, in September 1994 resulted in the deaths of 14 racing horses and a horse trainer. The causative agent was a new member of the family Paramyxoviridae. The virus was originally called Equine morbillivirus but was renamed Hendra virus (HeV) when molecular characterization highlighted differences between it and members of the genus Morbillivirus. Less than 5 years later, the closely related Nipah virus (NiV) emerged in Malaysia, spread rapidly through the pig population, and caused the deaths of over 100 people. We report the characterization of the HeV L gene and protein, the genome termini, and gene boundary sequences, thus completing the HeV genome sequence. In the highly conserved region of the L protein, the HeV sequence GDNE differs from the GDNQ found in almost all other nonsegmented negative-strand (NNS) RNA viruses. HeV has an absolutely conserved intergenic trinucleotide sequence, 3'-GAA-5', and highly conserved transcription initiation and termination sequences similar to those of respiroviruses and morbilliviruses. The large genome size (18,234 nucleotides), the unique complementary genome terminal sequences of HeV, and the limited homology with other members of the Paramyxoviridae suggest that HeV, together with NiV, should be classified in a new genus in this family. The large genome of HeV also fills a gap in the spectrum of genome sizes observed with NNS RNA virus genomes. As such, it provides a further piece in the puzzle of NNS RNA virus evolution.

Amino Acid Sequence↗
PubMed1999

Single-cell volume estimation by three-dimensional wide-field microscopy applied to astroglial primary cultures.

Astrocytes, which constitute a prominent part of the number and volume of brain cells, have a high capacity for controlling their volume, and astrocytic swelling is associated with a number of pathological states affecting the CNS. In order to understand the mechanisms for regulating cell volume in astrocytes better, it is of utmost importance to develop technical instrumentation and analysis methods capable of detecting and characterizing dynamic cell shape changes in a quantitative and robust way. For this purpose, a new method was developed to quantify changes in cell volume at the single-cell level. This method is based on three-dimensional (3D) fluorescence imaging obtained by optical sectioning. An automated image acquisition system was developed for the collection of two-dimensional (2D) microscopic images. A deblurring algorithm was implemented in order to restore the originally unfocused image content. Advanced image analysis techniques were applied for accurate and automated determination of cell volume. The sensitivity and reproducibility of the method was evaluated by using fluorescent beads. The techniques were applied to fura-2-labeled astroglial cells in primary culture exposed to hypo- or hyperosmotic stress. The results show that this method is valuable for determining volume changes in cells or parts thereof.

Animals↗
PubMed1999

Delta-opioid receptor immunoreactivity on astrocytes is upregulated during mitosis.

Endogenous opioid peptides and opioid receptors are expressed by brain cells early during normal development, and exogenous opiate exposure in this period is known to affect brain cell proliferation and maturation. Despite the abundant evidence that opioids affect brain development, little is known about the mechanisms involved. In this study cortical astrocytes in primary culture were examined immunohistochemically by using antibodies against the opioid receptors. The immunoreactivity for delta-opioid receptors was strongly upregulated during mitosis with an increase in immunostaining that started in early prophase and lasted through the M-phase to cytokinesis. Similar effects could not be observed when antibodies against the mu- or kappa-opioid receptor subtypes were used. Cultured neurons and microglia presented a strong and homogenous immunostaining for the delta-opioid receptor and no further upregulation of immunoreactivity could be detected in these cells. The presence of functional delta-opioid receptors on the mitotic astrocytes was verified by using microspectrofluorometry for detection of delta-opioid agonist induced changes in intracellular free calcium concentrations ([Ca2+]i). In these experiments fluo-3/AM incubated cells showed a rapidly induced delta-opioid agonist (DPDPE, 10(-6) M) evoked increase in [Ca2+]i. These results suggest an upregulation of the delta-opioid receptors that could represent a mechanism involved in the response to opioids in the developing brain.

Animals↗
PubMed1999

5-Hydroxytryptamine and glutamate modulate velocity and extent of intercellular calcium signalling in hippocampal astroglial cells in primary cultures.

The effects of 5-hydroxytryptamine or glutamate treatment on mechanically induced intercellular calcium waves were studied in gap junction-coupled astroglial cells using rat astroglial-neuronal primary cultures from hippocampus. Imaging software was developed to study amplitude, velocity and extent of wave propagation. Velocity software was designed to find the cell contours automatically and to calculate travelled distance and time-delay of the calcium wave as it propagates from the stimulated cell to all other cells. Propagation analyses were performed to calculate the area of wave propagation. Mechanical stimulation of a single astroglial cell induced an intercellular calcium wave spreading from cell to cell in the astroglial syncytium. When registering the appearances of calcium signals in individual cells along the wave path upon re-stimulation of the same cell, 44.7% of the cells responded with similar calcium signal appearances the second time as the first time. A second wave from the opposite direction resulted in similar calcium signal appearances in 27.3% of the studied cells. Both amplitude and velocity of the calcium signal decreased most prominently in the first part and showed a later flattening out. Treatment with 5-hydroxytryptamine or glutamate for 20-30 s before mechanical stimulation increased the velocity of the calcium waves. 5-Hydroxytryptamine treatment for varying times decreased the propagation area of the calcium waves. In contrast, glutamate treatment increased the propagation area.

Animals↗