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K D Beck

Publications and source records attributed to K D Beck.

At least 19 recordsLinked to original sources
PubMed2004

Blockage of glucocorticoid, but not mineralocorticoid receptors prevents the persistent increase in circulating basal corticosterone concentrations following stress in the rat.

Exposure to a single session of intense inescapable stressors results in elevations of plasma corticosterone levels selective to the trough of the circadian rhythm that last for several days after stressor cessation. In the present study, we examined whether this stress-induced alteration in the regulation of the circadian trough is dependent upon glucocorticoid and/or mineralocorticoid receptor activation during stress. Pre-treatment with the mineralocorticoid receptor (MR) antagonist, spironolactone (RU-28318; 50 mg/kg, s.c.), and/or the glucocorticoid receptor (GR) antagonist, mifepristone (RU-38486; 50 mg/kg, s.c.) 1 h before inescapable stress (40, 2.0-mA tail-shocks delivered over a 1 h period) had no effect on the acute plasma corticosterone response to inescapable stress. Treatment with the MR antagonist alone did not affect the appearance of basal corticosterone elevations in stressed rats. However, the elevated trough plasma corticosterone levels were no longer evident in rats treated previously with the GR antagonist either alone or in combination with the MR antagonist. GR activation during stressor exposure appears to be necessary for the development of subsequent basal corticosterone elevations.

Adaptation, Physiological↗
PubMed2001

[Respiratory filters and pneumonia: many unresolved questions].

BACKGROUND AND OBJECTIVE: The use of heat and moisture exchanging filters (HMEF) instead of conventional heated humidifiers is a cost-effective method in intensive care medicine. It was the objective of this paper to investigate the evidence for HMEF from the viewpoint of prevention of pneumonia and to investigate the appropriate changing intervals as well as filter materials. METHOD: Randomised controlled trials published in recent years and focusing on prevention of pneumonia as well as other prospective controlled studies were reviewed systematically. RESULTS: The studies demonstrate neither a clear advantage nor disadvantage of HMEF. No final statement is possible concerning changing intervals and the most appropriate filter materials. However, the data give some evidence for a possible extension of changing intervals to 72 hours without harm to the patients and probably show very little influence of filter materials. CONCLUSION: Because of the economic advantages of HMEF instead of an active humidification, the use of filters--with the exception of contraindications for individual patients--should be preferred.

Filtration↗
PubMed2000

Progesterone and cocaine administration affect serotonin in the medial prefrontal cortex of ovariectomized rats.

Due to the hypothetical role of ovarian hormones, estrogen and progesterone, in cocaine-induced behavioral activity and self-administration, this study investigated the effects of cocaine, estrogen, and progesterone administration on monoamine levels in the medial prefrontal cortex of ovariectomized hormone-treated rats. Rats were given either 'binge' cocaine or saline, and one of four hormone treatments: vehicle, estrogen, progesterone, or estrogen+progesterone. The co-administration of progesterone and cocaine resulted in increased levels of serotonin when compared to saline-treated controls and cocaine-treated animals in the other hormone-treatment groups. Further, progesterone-treated rats had higher levels of 5-HIAA than vehicle or estrogen-treated rats. Although levels of dopamine, DOPAC, and homovanillic acid were decreased after cocaine, these alterations failed to reach significance. These results show an interaction between the endocrine environment and cocaine-induced alterations in serotonin system in the medial prefrontal cortex. Thus, these changes may contribute to previously reported gender and estrous cycle differences in behavioral responses to cocaine.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1999

Food deprivation modulates chronic stress effects on object recognition in male rats: role of monoamines and amino acids.

An object recognition task was used to determine if chronic restraint stress (6 h/day for 21 days) impairs non-spatial memory, since chronic restraint is known to impair spatial memory. In addition, food deprivation was tested as a possible modulating factor of any stress effect in this non-reward-dependent task. Following 3 weeks of daily restraint, subjects were tested for open field activity and object recognition (over different delay intervals) during one week in two separate experiments. Experiment 1 involved testing under low demand conditions (small arena) while experiment 2 involved testing under higher-demand conditions (large arena). Basal monoamine and amino acid levels (home cage) were assessed in experiment one and monoamine arousal levels (following a sample trial) were assessed in experiment two. We observed that chronic stress impaired object recognition when the delay was extended beyond 1 h, and that food deprivation could attenuate the degree of impairment. In addition, chronic stress was associated with increased norepinephrine levels in both the amygdala and hippocampus, and dopamine (HVA/DA, DOPAC/DA) in prefrontal cortex. These changes were not observed in stress subjects that were subsequently food deprived. Food deprived subjects had higher basal serotonin activity in prefrontal cortex and hippocampus as well as higher serum CORT levels. Results suggest that food deprivation may act as a novel stress, thereby increasing subjects' arousal and attention toward the objects, which aids stressed subjects, especially in low-demand conditions. Both restraint and food deprivation affected select limbic areas associated with memory functioning.

Amino Acids↗
PubMed1999

The gene encoding proline dehydrogenase modulates sensorimotor gating in mice.

Hemizygous cryptic deletions of the q11 band of human chromosome 22 have been associated with a number of psychiatric and behavioural phenotypes, including schizophrenia. Here we report the isolation and characterization of PRODH, a human homologue of Drosophila melanogaster sluggish-A (slgA), which encodes proline dehydrogenase responsible for the behavioural phenotype of the slgA mutant. PRODH is localized at chromosome 22q11 in a region deleted in some psychiatric patients. We also isolated the mouse homologue of slgA (Prodh), identified a mutation in this gene in the Pro/Re hyperprolinaemic mouse strain and found that these mice have a deficit in sensorimotor gating accompanied by regional neurochemical alterations in the brain. Sensorimotor gating is a neural filtering process that allows attention to be focused on a given stimulus, and is affected in patients with neuropsychiatric disorders. Furthermore, several lines of evidence suggest that proline may serve as a modulator of synaptic transmission in the mammalian brain. Our observations, in conjunction with the chromosomal location of PRODH, suggest a potential involvement of this gene in the 22q11-associated psychiatric and behavioural phenotypes.

Acoustic Stimulation↗
PubMed1998

Expression of the proto-oncogene Ret, a component of the GDNF receptor complex, persists in human substantia nigra neurons in Parkinson's disease.

The proto-oncogene Ret, a membrane-associated receptor protein tyrosine kinase, has recently been shown to be a component of the glial cell line-derived neurotrophic factor (GDNF) receptor complex. GDNF has potent dopaminergic neurotrophic properties and has been suggested as a treatment for Parkinson's disease (PD). In this study, tissue sections of human substantia nigra (SN) from normal and PD cases were examined to determine the pattern of Ret expression in this region, and whether there was continued Ret expression in surviving dopaminergic neurons in PD cases. Using a polyclonal antibody to the amino terminal of Ret, immunoreactivity was localized in the SN to dopaminergic neurons. The antibody predominantly identified punctate deposits within cells. A similar pattern of immunoreactivity was observed in rat and monkey SN neurons. In neurologically normal cases, immunoreactivity was detected in many of the SN neurons. In all the PD cases studied, continued expression of Ret was observed in many of the surviving dopaminergic neurons. In certain cases, it was also detected on cells with the morphology of microglia. Ret expression by microglia was confirmed by immunoblot analysis on the human THP-1 macrophage type cell line. However, these cells did not express the mRNA for GDNFRalpha, the other component of the GDNF receptor complex.

Adult↗
PubMed1998

Estradiol enhances learning and memory in a spatial memory task and effects levels of monoaminergic neurotransmitters.

The effects of chronic estrogen treatment on radial arm maze performance and on levels of central monoaminergic and amino acid neurotransmitters were examined in ovariectomized (Ovx) rats. In an eight arms baited paradigm, choice accuracy was enhanced following 12 days but not 3 days of treatment. In addition, performance during acquisition of the eight arms baited maze task was better in estrogen-treated Ovx rats than in Ovx rats. Performance of treated rats was also enhanced in win-shift trials conducted 12 days postestrogen treatment. Working, reference, and working-reference memory was examined when four of the eight arms were baited, and only working memory was improved by estrogen and only after long-term treatment. Activity of Ovx rats on an open field, crossings and rearings, was increased at 5 but not at 35 days following estrogen treatment. In medial prefrontal cortex, levels of NE, DA, and 5-HT were decreased but glutamate and GABA levels were not affected following chronic estrogen treatment. Basal forebrain nuclei also showed changes in monoamines following estrogen. Hippocampal subfields showed no effects of estrogen treatment on monoaminergic or amino acid transmitters. Levels of GABA were increased in the vertical diagonal bands following chronic estrogen. Results show that estrogen enhances learning/memory on a task utilizing spatial memory. Effects in Ovx rats appear to require the chronic (several days) presence of estrogen. Changes in activity of both monoaminergic and amino acid transmitters in the frontal cortex and basal forebrain may contribute to enhancing effects of estrogen on learning/memory.

Animals↗
PubMed1998

Characterization of two distinct monoclonal antibodies specific for glial cell line-derived neurotrophic factor.

Here we report the generation and characterization of two distinct monoclonal antibodies, G-90 and B-1531, specific to glial cell line-derived neurotrophic factor (GDNF). ELISA results confirmed that G-90 and B-1531 both recognize GDNF. Western blots showed that G-90 recognized only the GDNF dimer, whereas B-1531 recognized both the monomer and dimer. Peptide competition ELISA (PCE) and BIAcore data suggested that G-90 and B-1531 recognize different epitopes: PCE confirmed that B-1531 binds to NH2-terminal peptides between amino acids 18 and 37, whereas G-90 does not; BIAcore data showed that B-1531 binds to the NH2 terminus of GDNF, whereas G-90 does not. G-90, in a concentration-dependent manner, completely neutralized the GDNF-induced increases of choline acetyltransferase in cultured motoneuron and of dopamine uptake and morphological differentiation in dopaminergic neuron cultures. B-1531 had no neutralizing effects. GDNF-induced Ret autophosphorylation in NGR-38 cells was completely neutralized by G-90, whereas B-1531 had a moderate effect. These data show that G-90 and B-1531 are specific antibodies to GDNF. The data also suggest that the NH2 terminus of GDNF is not critical for activity. Partial inhibition of Ret phosphorylation is insufficient to down-regulate GDNF-induced biological activity.

Animals↗
PubMed1998

Inhibition of phosphatidylinositol 3-kinase activity blocks cellular differentiation mediated by glial cell line-derived neurotrophic factor in dopaminergic neurons.

Glial cell line-derived neurotrophic factor (GDNF) is a potent survival factor for midbrain dopaminergic neurons. To begin to understand the intracellular signaling pathways used by GDNF, we investigated the role of phosphatidylinositol 3-kinase activity in GDNF-stimulated cellular function and differentiation of dopaminergic neurons. We found that treatment of dopaminergic neuron cultures with 10 ng/ml GDNF induced maximal levels of Ret phosphorylation and produced a profound increase in phosphatidylinositol 3-kinase activity, as measured by western blot analysis and lipid kinase assays. Treatment with 1 microM 2-(4-morpholinyl)-8-phenylchromone (LY294002) or 100 nM wortmannin, two distinct and potent inhibitors of phosphatidylinositol 3-kinase activity, completely inhibited GDNF-induced phosphatidylinositol 3-kinase activation, but did not affect Ret phosphorylation. Furthermore, we examined specific biological functions of dopaminergic neurons: dopamine uptake activity and morphological differentiation of tyrosine hydroxylase-immunoreactive neurons. GDNF significantly increased dopamine uptake activity and promoted robust morphological differentiation. Treatment with LY294002 completely abolished the GDNF-induced increases of dopamine uptake and morphological differentiation of tyrosine hydroxylase-immunoreactive neurons. Our findings show that GDNF-induced differentiation of dopaminergic neurons requires phosphatidylinositol 3-kinase activation.

Androstadienes↗
PubMed1997

Inhibition of glial cell line-derived neurotrophic factor induced intracellular activity by K-252b on dopaminergic neurons.

The c-ret protooncogene encodes Ret, the functional tyrosine kinase receptor for glial cell line-derived neurotrophic factor (GDNF). K-252b, a known protein tyrosine kinase inhibitor, has been shown earlier to inhibit the trophic activity of brain-derived neurotrophic factor on dopaminergic (DAergic) neurons and nerve growth factor on basal forebrain cholinergic neurons while potentiating neurotrophin-3 activity on central cholinergic and peripheral sensory neurons and PC12 cells. We tested whether K-252b would modulate GDNF-induced differentiation in DAergic neuron cultures. Exposure to 1 ng/ml GDNF increased dopamine (DA) uptake 80% above control, whereas treatment with 5 microM K-252b decreased the efficacy of GDNF by 60%. Concentrations of GDNF of <100 pg/ml were completely inhibited, whereas concentrations of >100 pg/ml were moderately active, between 10 and 20% above control. In addition, K-252b shifted the ED50 from 20 to 200 pg/ml. GDNF treatment increased soma size and neurite outgrowth in tyrosine hydroxylase-immunoreactive neurons. K-252b inhibited differentiation of these morphological parameters induced by GDNF. Furthermore, GDNF stimulated Ret autophosphorylation at maximal levels, whereas the inhibition of DA uptake and morphological differentiation by K-252b correlated with a significantly decreased level of Ret autophosphorylation. Therefore, K-252b is able to inhibit intracellular activities induced by GDNF on mesencephalic DAergic neurons.

Animals↗
PubMed1996

GDNF induces a dystonia-like state in neonatal rats and stimulates dopamine and serotonin synthesis.

To test whether glial cell line-derived neurotrophic factor (GDNF) regulates the development of nigral dopaminergic neurons in vivo, neonatal rats received bilateral injections of GDNF into the striatum. Injections at postnatal day 2 induced a unique transient behavioral pattern characterized by forelimb hyperflexure, clawed toes of all limbs, and a kinked tail. Parallel to the behavioral changes, the levels of striatal and ventral mesencephalic dopamine and serotonin were increased from 60% to 100% with a proportional increase of principal metabolite levels. GDNF increased tyrosine hydroxylase activity in the ventral mesencephalon, but did not affect striatal activity of choline acetyltransferase and GABA uptake. GDNF failed to induce sprouting of dopaminergic neurites. Our findings suggest that during development striatal GDNF regulates the capacity of dopaminergic and of serotonergic neurons for neurotransmitter production and release.

Animals↗
PubMed1995

Mesencephalic dopaminergic neurons protected by GDNF from axotomy-induced degeneration in the adult brain.

Glial-cell-line-derived neurotrophic factor (GDNF) promotes survival of embryonic dopaminergic neurons in culture, and its expression pattern suggests a role as a transient target-derived trophic factor for dopaminergic neurons of the substantia nigra. These neurons participate in the control of motor activity, emotional status and cognition, and they degenerate in Parkinson's disease for unknown reasons. To test whether GDNF has a trophic effect on dopaminergic neurons in the adult brain, we used a rat model in which these neurons are induced to degenerate by transecting their axons within the medial forebrain bundle. We report here that axotomy resulted in loss of half the tyrosine hydroxylase-expressing neurons in the substantia nigra. This loss was largely prevented by repeated injections of GDNF adjacent to the substantia nigra. Our findings suggest that GDNF or related molecules may be useful for the treatment of Parkinson's disease.

Animals↗
PubMed1995

Retrograde transport of nerve growth factor from hippocampus and amygdala to trkA messenger RNA expressing neurons in paraventricular and reuniens nuclei of the thalamus.

We previously reported the presence of trkA messenger RNA expressing non-cholinergic neurons in the paraventricular anterior and reuniens nuclei, which are located in the thalamic midline. In the present study, retrograde labeling with iodinated (125I) nerve growth factor was used to identify the innervation target of these cells. Neurons in the paraventricular anterior and reuniens nuclei were labeled following injection of iodinated nerve growth factor into amygdala and hippocampus, but not into nucleus accumbens and entorhinal cortex, the two other main areas receiving strong innervation from the thalamic midline. Target ablation of hippocampus or amygdala failed to down-regulate trkA messenger RNA expression in the two thalamic nuclei, thus suggesting a role for nerve growth factor different from a critical survival factor. The thalamic paraventricular anterior and reuniens nuclei are part of the reticular formation which plays a role in general cortical activation, behavioral arousal and control of awareness. Retrograde transport of nerve growth factor by trkA messenger RNA expressing neurons in these nuclei suggests a physiological role of this trophic factor in the function of these cells.

Amygdala↗
PubMed1995

Differential regulation of catalytic and non-catalytic trkB messenger RNAs in the rat hippocampus following seizures induced by systemic administration of kainate.

Ribonuclease protection analysis and quantitative in situ hybridization histochemistry were used to investigate the coordination and regional expression of catalytic and non-catalytic trkB messenger RNAs in the adult rat hippocampus following systemic kainate-induced seizures. Changes in trkB expression were compared with the messenger RNA expression of its neurotrophic ligands, brain-derived neurotrophic factor and neurotrophin-3. TrkB messenger RNA expression was increased in the dentate granule cells at 1-4 h following the onset of seizures, and returned to control levels 16-24 h thereafter. In addition, seizures also induced expression of trkB messenger RNA in putative non-neuronal cells at four to seven days in the molecular layer of the dentate gyrus and the stratum lacunosum moleculare of the CA1 region. Hybridization with probes specific for the non-catalytic trkB receptor and the catalytic trkB receptor revealed that the increases at four and seven days in the molecular layers of the hippocampus reflected an up-regulation of only the non-catalytic form of the receptor. Furthermore, the neuronal increases observed 1-4 h were due to an up-regulation of both trkB TK- and trkB TK+ messenger RNAs. It was established that systemic administration of kainate increased brain-derived neurotrophic factor messenger RNA levels in the pyramidal and granule cell regions of the hippocampus 1-4 h following the onset of behaviorally manifested seizure activity. Early changes in neuronal expression of trkB TK- and trkB TK+ messenger RNA paralleled changes in brain-derived neurotrophic factor messenger RNA in the dentate granule cell and CA1 pyramidal cell layers, but not in the CA3 subregion. These data suggest that concomitant regulation of brain-derived neurotrophic factor and its cognate receptor may play a role in the selective vulnerability of hippocampal subregions to kainate-induced neuropathology. Furthermore, these data suggest a dual function for trkB receptor expression in the hippocampus following kainate-induced seizures, possibly related to both the plastic and degenerative consequences of seizure induction by kainate.

Animals↗