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P Gass

Publications and source records attributed to P Gass.

At least 55 records · Page 3Linked to original sources
PubMed1997

Expression of activating transcription factor-2, serum response factor and cAMP/Ca response element binding protein in the adult rat brain following generalized seizures, nerve fibre lesion and ultraviolet irradiation.

The expression of the constitutive transcription factors activating transcription factor-2 (ATF-2), serum response factor (SRF) and cAMP/Ca response element binding factor (CREB), and the phosphorylation of SRF and CREB were studied in the untreated adult rat nervous system and following seizure activities and neurodegenerative stimuli. In the untreated rat, intense nuclear SRF immunoreactivity was present in the vast majority of neurons in the forebrain, cortex, striatum, amygdala and hippocampus, and in some scattered neurons in the medulla and spinal cord. In contrast, SRF immunoreactivity was absent in the midline areas of the forebrain, e.g., the globus pallidum and septum, and in the hypothalamus, thalamus, mesencephalon and motoneurons. Nuclear ATF-2 was expressed at high levels in apparently all neurons, but not glial cells, throughout the neuraxis except for those neuronal populations which exhibit a high basal level of c-Jun, i.e. dentate gyrus and the motoneurons of cranial and somatosensory neurons. CREB immunoreactivity was present at a rather uniform intensity in all neuronal and glial cells throughout the neuraxis. Two hours, but not 5 h or 24 h, following systemic application of kainic acid, an increase in SRF was detectable by western blot analysis in hippocampal and cortical homogenates whereas the expression of ATF-2 and CREB did not change. Phosphorylation of CREB at serine 133 and of SRF at serine 103 were studied with specific antisera. In untreated rats, intense phosphoCREB and phosphoSRF immunoreactivities labelled many glial cells and/or neurons with the highest levels in the dentate gyrus, the entorhinal cortex and the retrosplenial cortex. Following kainate-induced seizures, phosphoSRF-IR but not phosphoCREB-IR transiently increased between 0.5 h and 2 h. Following transection of peripheral or central nerve fibres such as optic nerve, medial forebrain bundle, vagal and facial nerve fibres, ATF-2 rapidly decreased in the axotomized neurons during that period when c-Jun was rapidly expressed. SRF remained unchanged and CREB disappeared in some axotomized subpopulations. Similar to axotomy, c-Jun increased and ATF-2 decreased in cultured adult dorsal root ganglion neurons following ultraviolet irradiation. The distribution of SRF and ATF-2 suggests that their putative target genes c-fos, junB, krox-24 and c-jun can be independently regulated from SRF and ATF-2. The suppression of ATF-2 and the expression of c-Jun following axotomy and ultraviolet irradiation might be part of a novel neuronal stress response in the brain that strongly resembles the stress response characterized in non-neuronal cells.

Activating Transcription Factor 2↗
PubMed1997

Effect of global system for mobile communication microwave exposure on the genomic response of the rat brain.

The acute effect of global system for mobile communication (GSM) microwave exposure on the genomic response of the central nervous system was studied in rats by measuring changes in the messenger RNAs of hsp70, the transcription factor genes c-fos and c-jun and the glial structural gene GFAP using in situ hybridization histochemistry. Protein products of transcription factors, stress proteins and marker proteins of astroglial and microglial activation were assessed by immunocytochemistry. Cell proliferation was evaluated by bromodeoxyuridine incorporation. A special GSM radiofrequency test set, connected to a commercial cellular phone operating in the discontinuous transmission mode, was used to simulate GSM exposure. The study was conducted at time averaged and brain averaged specific absorption rates of 0.3 W/kg (GSM exposure), 1.5 W/kg (GSM exposure) and 7.5 W/kg (continuous wave exposure), respectively. Immediately after exposure, in situ hybridization revealed slight induction of hsp70 messenger RNA in the cerebellum and hippocampus after 7.5 W/kg exposure, but not at lower intensities. A slightly increased expression of c-fos messenger RNA was observed in the cerebellum, neocortex and piriform cortex of all groups subjected to immobilization, but no differences were found amongst different exposure conditions. C-jun and GFAP messenger RNAs did not increase in any of the experimental groups. 24 h after exposure, immunocytochemical analysis of FOS and JUN proteins (c-FOS, FOS B, c-JUN JUN B, JUN D), of HSP70 or of KROX-20 and -24 did not reveal any alterations. Seven days after exposure, neither increased cell proliferation nor altered expression of astroglial and microglial marker proteins were observed. In conclusion, acute high intensity microwave exposure of immobilized rats may induce some minor stress response but does not result in lasting adaptive or reactive changes of the brain.

Animals↗
PubMed1997

SHARPs: mammalian enhancer-of-split- and hairy-related proteins coupled to neuronal stimulation.

In the mammalian central nervous system, a diverse group of basic helix-loop-helix (bHLH) proteins is involved in the determination of progenitor cells and, subsequently, in regulating neuronal differentiation. Here we report the identification of a novel subfamily of bHLH proteins, defined by two mammalian enhancer-of-split- and hairy-related proteins, termed SHARP-1 and SHARP-2. In contrast to known bHLH genes, detectable transcription of SHARP genes begins at the end of embryonic development marking differentiated neurons that have reached a final position, and increases as postnatal development proceeds. In the adult, SHARP genes are expressed in subregions of the CNS that have been associated with adult plasticity. In PC12 cells, a model system to study neurite outgrowth, SHARP genes can be induced by NGF with the kinetics of an immediate-early gene. Similarly, within 1 h after the administration of kalnic acid in vivo, SHARP-2 is induced in neurons throughout the rat cerebral cortex. This suggests that neuronal bHLH proteins are also involved in the "adaptive" changes of mature CNS neurons which are coupled to glutamatergic stimulation.

Amino Acid Sequence↗
PubMed1996

Transient expression of the mitogen-activated protein kinase phosphatase MKP-1 (3CH134/ERP1) in the rat brain after limbic epilepsy.

The immediate early gene-encoded enzyme, MAP kinase phosphatase 1 (MKP-1), is thought to be a key element in controlling cellular signalling pathways activated by MAP kinases. Since MAP kinase have been demonstrated to participate in neuronal stimulus-transcription coupling following seizure activity, the present study investigated the induction of MKP-1 in the rat brain after limbic epilepsy. MKP-1 expression was studied with a polyclonal antiserum by Western blots, immunocytochemistry and immuno-electron microscopy at different time periods between 1 and 24 h after kainic acid-induced limbic seizures. MKP-1 induction was identified in dentate granule cells of the hippocampus but not in pyramidal neurons, furthermore in neurons of the outer layers of the neocortex, as well as in neurons of the lateral nucleus of the bed of the stria terminalis. Immuno-electron microscopy demonstrated that MKP-1 was localized in the neuronal nucleus, where the substrate of MKP-1, activated MAP kinases, are also found. In view of the restricted areas of MKP-1 expression and the widespread areas of altered MAP kinases activity it can be concluded that in the majority of CNS populations other mechanisms than MKP-1 induction are responsible for the shut-off of MAP kinases following seizure activity. MKP-1 may contribute in the specific subpopulations where it is induced to the post-translational control of inducible transcription factors of the fos, jun and myc family.

Animals↗
PubMed1996

Reduction of morphine abstinence in mice with a mutation in the gene encoding CREB.

Chronic morphine administration induces an up-regulation of several components of the cyclic adenosine 5'-monophosphate (cAMP) signal transduction cascade. The behavioral and biochemical consequences of opiate withdrawal were investigated in mice with a genetic disruption of the alpha and Delta isoforms of the cAMP-responsive element-binding protein (CREB). In CREBalphadelta mutant mice the main symptoms of morphine withdrawal were strongly attenuated. No change in opioid binding sites or in morphine-induced analgesia was observed in these mutant mice, and the increase of adenylyl cyclase activity and immediate early gene expression after morphine withdrawal was normal. Thus, CREB-dependent gene transcription is a factor in the onset of behavioral manifestations of opiate dependence.

Adenylyl Cyclases↗
PubMed1996

Targeting of the CREB gene leads to up-regulation of a novel CREB mRNA isoform.

To define the role of cAMP signaling in gene control, we have generated mice with a mutation in the cAMP response element binding protein (CREB) gene. Mice carrying this mutation are viable but show an impairment in memory consolidation. In further analysis of these mice, we have found an up-regulation of a CREB isoform that has not been described previously . The new isoform, termed CREB beta, has nearly the same transactivation potential as the other CREB isoforms and is expressed ubiquitously. The up-regulation appears to be due to an increase in alternative splicing or mRNA stability, but not to an increase in transcriptional rate. Due to the relatively low levels of expression in all tissues, the role of this isoform is likely to be minor in the wild-type mouse. However, its dramatic up-regulation in the mutant mouse, together with the specific deficiencies recently observed in these mice, suggest that it has a very specific role in compensating for CREB alpha and delta in some, but not all, areas where CREB function has been implicated. Together with the up-regulation of the cAMP response element modulator protein (CREM) mRNA and protein levels demonstrated previously in CREB mutant mice, we suggest that the up-regulation of CREB beta may also contribute to compensation within the CREB/ATF family of transcription factors, when CREB delta and CREB alpha are absent.

Alternative Splicing↗
PubMed1996

[Magnetic resonance tomography of vasogenic brain edema in animal experiments].

PURPOSE: To systematically evaluate modern magnetic resonance imaging (MRI) techniques of studying brain oedema, an animal model of vasogenic oedema is needed. MATERIAL AND METHODS: We developed such a model by stereotactically cannulating the caudate nucleus in 11 Wistar-rats and infusing a solution of albumin. The way the oedema developed was imaged by MRI and then correlated histologically (three animals) and macroscopically after infusion of Evans' blue (two animals). RESULTS: The extension of the infusion oedema was the same in both MRI and histology as well as at direct inspection of the specimen after infusion of Evans blue. With continuous acquisition of T1-weighted images after infusion of a 1% solution of Gd-DTPA we were able to demonstrate the dynamics of oedema evolution and bulk flow. CONCLUSION: We believe that this infusion oedema is a suitable model for systematically investigating both signal behaviour and pathogenesis of vasogenic brain oedema by MRI.

Animals↗
PubMed1996

Editing of GluR2 RNA in the gerbil hippocampus after global cerebral ischemia.

Postischemic delayed neuronal death (DND) in CA1 of the gerbil hippocampus is thought to be caused by an abnormal increase of Ca2+ influx into the cell, mediated by excessive activation of glutamate receptors. One subtype of glutamate receptors, the AMPA receptor, is not permeable to calcium ions as long as an edited form of its GluR2 subunit is present. It is possible that global ischemia interferes with the posttranscriptional editing of the GluR2 mRNA and thus leads to calcium influx via the AMPA receptor. In order to test this hypothesis, we examined the extent of GluR2 RNA editing in CA1 and CA3 microdissected from gerbil hippocampus after 5 min of global ischemia and various recirculation intervals. At each interval tested, quality and quantity of mRNA editing in the vulnerable CA1 region were the same as in CA3. Furthermore, postischemic mRNA editing in both hippocampal regions was indistinguishable from editing in untreated control animals. Our results clearly demonstrate that global ischemia does not cause impairment of GluR2 RNA editing, which is thus not responsible for the abnormal calcium permeability of the postischemic cell membrane.

Animals↗
PubMed1995

Embryonic cortical neurons differentiate into various types of interneurons when heterotopically transplanted into the adult rat brain.

The adult cortex represents a heterogeneous mixture of different classes of pyramidal neurons and non-pyramidal interneurons. After grafting embryonic cortical anlage into the adult striatum, the present study investigated whether the development of different populations of interneurons in heterotopic cortical grafts is similar to the adult cortex. The presence of specific subpopulations of interneurons in grafts was assessed by immunocytochemistry using various antibodies against marker molecules for interneurons such as neuropeptides and calcium-binding proteins. These molecules are expressed to a different extent in specific subpopulations of cortical interneurons. Cortical primordia obtained on embryonic day 14 (E14) were stereotactically grafted into the center of the left striatum of adult recipient rats. After an 8-week differentiation period, host rats were perfusion fixed and immunocytochemistry was performed using antibodies against neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), somatostatin, parvalbumin and calbindin D-28k. Within the grafts, the number of immunopositive interneurons as well as the intensity of immunostaining for different marker molecules corresponded well with those of the adult cortex. In contrast, the expression pattern in the graft demonstrated clear differences when compared with the surrounding host striatum. The present study demonstrates, that at E14 at least some cells of the cortical anlage are primed to develop into different classes of interneurons independent of their normal environment and their regular synaptic connections. Thus, different interneuron progenitor cells survive transplantation and develop cell-specific morphological and cytochemical characteristics. Differentiation into various subpopulations of neurons may be a prerequisite for potential therapeutic approaches in humans.

Age Factors↗
PubMed1995

Early-onset epilepsy and postnatal lethality associated with an editing-deficient GluR-B allele in mice.

The arginine residue at position 586 of the GluR-B subunit renders heteromeric alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)-sensitive glutamate receptor channels impermeable to calcium. The codon for this arginine is introduced at the precursor messenger RNA (pre-mRNA) stage by site-selective adenosine editing of a glutamine codon. Heterozygous mice engineered by gene targeting to harbor an editing-incompetent GluR-B allele synthesized unedited GluR-B subunits and, in principal neurons and interneurons, expressed AMPA receptors with increased calcium permeability. These mice developed seizures and died by 3 weeks of age, showing that GluR-B pre-mRNA editing is essential for brain function.

Alleles↗
PubMed1995

Manganese and chronic hepatic encephalopathy.

Clinical observations and animal studies have raised the hypothesis that increased concentrations of manganese (Mn) in whole blood might lead to accumulation of this metal within the basal ganglia in patients with end-stage liver disease. We studied ten patients with liver failure (and ten controls) by magnetic resonance imaging (MRI) and measurement of Mn in brain tissue of three patients who died of progressive liver failure (and three controls) was also done. Whole blood Mn concentrations in patients with liver cirrhosis were significantly increased (median 34.4 micrograms/L vs 10.3 micrograms/L in controls; p = 0.0004) and pallidal signal intensity indices correlated with blood Mn (Rs = 0.8, p = 0.0058). Brain tissue samples reveal highest Mn concentrations in the caudate nucleus, followed by the quadrigeminal plate and globus pallidus. Mn accumulates within the basal ganglia in liver cirrhosis. Similarities between Mn neurotoxicity and chronic hepatic encephalopathy suggest that this metal may have a role in the pathogenesis of chronic hepatic encephalopathy. Further studies are warranted because the use of chelating agents could prove to be a new therapeutic option to prevent or reverse this neuropsychiatric syndrome.

Adult↗
PubMed1995

Comparison of frequency-specific c-Fos expression and fluoro-2-deoxyglucose uptake in auditory cortex of gerbils (Meriones unguiculatus).

Induction of c-Fos in the auditory cortex of gerbils was investigated immunocytochemically 1 h after single, triple or 1 h continuous stimulation with a series of narrow band frequency-modulated tone bursts. With single stimulation c-Fos immunoreactive neurons were chiefly found in the primary auditory field (AI), where they formed a narrow frequency-specific column across layers II-VI. Side-band-like patterns adjacent to this column appeared characteristically with triple stimulation. Immunoreactive cell density in the anterior auditory field and the caudal fields was sparse and location not frequency specific with single or triple stimulation. Spatial comparisons of c-Fos immunoreactive neuron density with 2-deoxy-2-fluoro-D-glucose (FDG) autoradiography in the same animals after 1 h of stimulation revealed spreading of c-Fos expression in neurons across the tonotopic maps of the AI and in the rostral and caudal fields of the auditory cortex. The pattern of the highest density of c-Fos labelled cells in the AI still matched the peak labelling of FDG autoradiographs. The results show that the postsynaptic marker c-Fos reflects the frequency representation in the AI with single or triple stimulation yet with a higher spatial resolution than the deoxyglucose technique. Longer stimulation causes nontonotopic intracortical spreading of the c-Fos-inducing message, a phenomenon potentially reflecting the effects of cooperativity in the maps.

Animals↗
PubMed1995

Effects of kainic acid induced seizures on immediate early gene expression in mice with a targeted mutation of the CREB gene.

The present study examined the response of immediate early genes following kainic acid induced seizures in mice lacking the alpha and delta isoforms of CREB. mRNA levels for c-fos, c-jun, and Krox-24 were measured following limbic seizure activity and were found to be induced in wild type as well as CREB mutant mice. This effect was also seen for these three mRNAs at the protein level as well as for FOS-B. Furthermore the time course of expression of FOS, JUN, KROX-24, and FOS-B proteins were essentially the same in CREB mutant mice as compared to wild-type controls. These data suggest that CREB alpha and delta are not required for the induction of immediate early genes following pharmacologically induced seizures.

Activating Transcription Factor 2↗
PubMed1995

Developmental expression of GAP-43 and SNAP-25 in heterotopic rat cortical grafts.

In situ hybridization techniques were used to assess (i) whether the temporal developmental profiles of the nervous system specific growth associated phosphoprotein (GAP-43) and the 25-kDa synaptosomal-associated protein (SNAP-25) are maintained in heterotopic cortical transplants, and (ii) whether the hybridization intensity in morphologically differentiated heterotopic transplants is comparable to that in the cortex of host animals. Cortical primordia at embryonic day 14 were stereotactically grafted into the striatum of adult recipient rats. Grafts at days 4, 7, 14, 35 and 56 after transplantation demonstrated developmental changes with a progressive decline of GAP-43 and a continuous up-regulation of SNAP-25 expression. Our data provide evidence of distinct molecular alterations during the differentiation process of cortical grafts, which are strikingly similar to previous studies investigating the temporal profile and intensity of GAP-43 and SNAP-25 gene expression in normal developing cortex of the rat.

Animals↗
PubMed1995

Basal expression of the inducible transcription factors c-Jun, JunB, JunD, c-Fos, FosB, and Krox-24 in the adult rat brain.

Jun, Fos, and Krox proteins are inducible transcription factors contributing to the control of gene expression. The elucidation of their individual expression patterns in the nervous system provides new insights into the ability of neurons to react with changes of gene expression to external stimulation under physiological or pathological conditions. The expression of c-Jun, JunB, JunD, c-Fos, FosB, and Krox-24 was investigated in the brain of untreated male Sprague-Dawley and female BDIX rats by immunocytochemistry using specific antibodies. JunD immunoreactivity (IR) labeled the highest number of neurons, being present in almost all neurons of the brain. JunD was expressed at high levels in those areas that also exhibit c-Jun, JunB, c-Fos, and FosB-IR, such as locus coeruleus, periolivary nuclei (ncl.), pontine and central gray, lateral lemniscal ncl., inferior and superior colliculi, leaflet of geniculate ncl., midline nuclei of thalamus, dorsomedial and paraventricular ncl. of hypothalamus, ncl. supraopticus, dorsolateral part of caudate putamen and lateral septal ncl. In contrast to the high number of JunD-positive neurons, c-Jun, JunB, c-Fos, and FosB proteins were detected in rather low numbers of neurons in these brain areas; the rank of the number of immunopositive neurons was c-Fos > JunB > c-Jun > FosB. Particularly high levels of expression were observed for c-Jun in medullary motoneurons, medial geniculate ncl., arcuate ncl., and dentate gyrus, and for JunB in the CA-1 area of the hippocampus and islands of Calleja. The zinc finger protein Krox-24 was expressed in many neurons of these brain areas, with only discrete Jun- and Fos-IR; additionally, many intensely labeled nuclei were present in spinal ncl. of the trigeminal ventromedial ncl. of the hypothalamus and the CA-1 area of the hippocampus. In the cerebellum, nuclear labeling was detected only for c-Jun, JunD, and Krox-24 in granule cells. JunD-IR was also found in glial cells of gray matter and fiber tracts, whereas glial c-Jun-IR was observed only in fiber tracts. Apart from a weak JunD-IR, some areas did not express Jun, Fos, and Krox proteins such as cuneate and gracile ncl., venterobasal complex of thalamus, globus pallidum, and Purkinje cells of the cerebellum. Our data indicate that inducible transcription factors of the fos, jun, and krox gene families show patterns of individual expression in untreated animals, thereby reflecting different mechanisms and/or thresholds for induction under physiological conditions.

Animals↗
PubMed1995

Quantitation of human cytomegalovirus genomes in the brain of AIDS patients.

Human cytomegalovirus (HCMV) is one of the major pathogens causing neurologic disease in the immunocompromised host. A competitive nested polymerase chain reaction (PCR) was used to determine DNA load, distribution, and sequence variability of HCMV genomes in the brain of AIDS patients with and without HCMV encephalitis confirmed by histology and immunocytochemistry. By quantitative PCR, HCMV genomes were found to be distributed diffusely in the central nervous system (CNS) of all five patients with histologically proven HCMV encephalitis, but also in the brain of five of eight AIDS patients without neuropathological evidence of HCMV encephalitis. The viral DNA load in cases with HCMV encephalitis was increased 10- to 1,000-fold as compared to patients without evidence of encephalitis. A viral load above 6,000 copies HCMV/10(6) copies beta-globin was found to be highly suggestive for HCMV encephalitis. Characterization of PCR products by temperature gradient gel electrophoresis (TGGE) and direct sequencing allowed us to detect a sequence variability of the amplified fragment of HCMV glycoprotein B (gB) among different patients, but also among different HCMV foci within the same patient. Furthermore, two of five AIDS patients with HCMV encephalitis most likely experienced double infections with different HCMV strains. The experimental procedure described in this study should also be applicable to the detection of significant HCMV DNA levels in biopsy samples.

AIDS-Related Opportunistic Infections↗
PubMed1995

c-JUN, KROX-24, and c-FOS expression in hippocampal grafts placed in excitotoxic hippocampal lesions of the rat.

Hippocampal transplants were examined for the expression of three specific immediate early gene encoded proteins in order to establish if grafted immature tissue maintains the basic molecular program necessary for gene transcription after grafting to excitotoxic (ibotenic acid-induced) lesions in adult host rat brains. The transplants were derived from newborn donor rats and were analyzed immunocytochemically for the presence of c-JUN, KROX-24, and c-FOS transcription factors 5 months after grafting. The expression and distribution patterns of these genes in the host hippocampus were identical to those in hippocampal neurons of normal untreated animals. c-JUN-, KROX-24-, and c-FOS-labeled neurons were also present in the transplants, where KROX-24 and c-FOS exhibited a distribution similar to host hippocampus. In contrast, c-JUN was more extensively expressed in the transplants, suggesting a molecular response to the grafting conditions and the actual graft-host brain interactions.

Animals↗