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W Gottschalk

Publications and source records attributed to W Gottschalk.

18 recordsLinked to original sources
PubMed2000

The role of brain-derived neurotrophic factor receptors in the mature hippocampus: modulation of long-term potentiation through a presynaptic mechanism involving TrkB.

The neurotrophin BDNF has been shown to modulate long-term potentiation (LTP) at Schaffer collateral-CA1 hippocampal synapses. Mutants in the BDNF receptor gene trkB and antibodies to its second receptor p75NTR have been used to determine the receptors and cells involved in this response. Inhibition of p75NTR does not detectably reduce LTP or affect presynaptic function, but analyses of newly generated trkB mutants implicate TrkB. One mutant has reduced expression in a normal pattern of TrkB throughout the brain. The second mutant was created by cre-loxP-mediated removal of TrkB in CA1 pyramidal neurons of this mouse. Neither mutant detectably impacts survival or morphology of hippocampal neurons. TrkB reduction, however, affects presynaptic function and reduces the ability of tetanic stimulation to induce LTP. Postsynaptic glutamate receptors are not affected by TrkB reduction, indicating that BDNF does not modulate plasticity through postsynaptic TrkB. Consistent with this, elimination of TrkB in postsynaptic neurons does not affect LTP. Moreover, normal LTP is generated in the mutant with reduced TrkB by a depolarization-low-frequency stimulation pairing protocol that puts minimal demands on presynaptic terminal function. Thus, BDNF appears to act through TrkB presynaptically, but not postsynaptically, to modulate LTP.

Animals↗
PubMed1999

Impairments in high-frequency transmission, synaptic vesicle docking, and synaptic protein distribution in the hippocampus of BDNF knockout mice.

Brain-derived neurotrophic factor (BDNF) promotes long-term potentiation (LTP) at hippocampal CA1 synapses by a presynaptic enhancement of synaptic transmission during high-frequency stimulation (HFS). Here we have investigated the mechanisms of BDNF action using two lines of BDNF knockout mice. Among other presynaptic impairments, the mutant mice exhibited more pronounced synaptic fatigue at CA1 synapses during high-frequency stimulation, compared with wild-type animals. Quantitative analysis of CA1 synapses revealed a significant reduction in the number of vesicles docked at presynaptic active zones in the mutant mice. Synaptosomes prepared from the mutant hippocampus exhibited a marked decrease in the levels of synaptophysin as well as synaptobrevin [vesicle-associated membrane protein (VAMP-2)], a protein known to be involved in vesicle docking and fusion. Treatment of the mutant slices with BDNF reversed the electrophysiological and biochemical deficits in the hippocampal synapses. Taken together, these results suggest a novel role for BDNF in the mobilization and/or docking of synaptic vesicles to presynaptic active zones.

Animals↗
PubMed1999

High-voltage-activated calcium channel messenger RNA expression in the 140-3 neuroblastoma-glioma cell line.

Expression of calcium channel alpha1 subunits in oocytes or cell lines has proven to be a powerful method in the analysis of structure-function relations, but these experimental systems are of limited value in the examination of neuron-specific functions such as transmitter release. Cell lines derived from neurons are often capable of these functions, but their intrinsic calcium channel alpha1 subunits are complicating factors in experimental design. We have examined the biophysical and molecular properties of calcium channels in a little studied neuroblastoma-glioma hybrid cell line, 140-3, a close relative of the NG108-15 cell line, to test whether this cell line might serve a role as an expression system for neural mechanisms. This cell was selected as it contains an intact transmitter release mechanism yet secretes little in response to depolarization. Patch-clamp recording revealed only a prominent low-threshold, rapidly inactivating calcium current with a single-channel conductance of approximately 7 pS that was identified as T type. A search for calcium channel alpha1 subunit messenger RNA in the 140-3 cells with three different tests only revealed alpha1C, whereas alpha1A-alpha1C were present in the parent NG108-15 line. We made a particular effort to search for alpha1E, since this subunit has been associated with a low-voltage-activated current. Our findings suggest that, since the principal nerve terminal-associated calcium channels (alpha1A, alpha1B, alpha1E) are absent in the 140-3 cell, this cell line may prove a particularly useful model for the analysis of the role of high-voltage-activated calcium channels in complex functions of neuronal cells.

Animals↗
PubMed1998

Presynaptic modulation of synaptic transmission and plasticity by brain-derived neurotrophic factor in the developing hippocampus.

In addition to the regulation of neuronal survival and differentiation, neurotrophins may play a role in synapse development and plasticity. Application of brain-derived neurotrophic factor (BDNF) promotes long-term potentiation (LTP) in CA1 synapses of neonatal hippocampus, which otherwise exhibit only short-term potentiation. This is attributable, at least in part, to an attenuation of the synaptic fatigue induced by high-frequency stimulation (HFS). However, the prevention of synaptic fatigue by BDNF could be mediated by an attenuation of synaptic vesicle depletion from presynaptic terminals and/or a reduction of the desensitization of postsynaptic receptors. Here we provide evidence supporting a presynaptic effect of BDNF. The effect of BDNF on synaptic fatigue depended on the stimulation frequency, not on the stimulus duration nor on the number of stimulation pulses. BDNF was only effective when the synapses were stimulated at frequencies >50 Hz. Treatment with BDNF also potentiated paired-pulse facilitation (PPF), a parameter reflecting changes in the properties of presynaptic terminals. This effect of BDNF was restricted only to PPF elicited with interpulse intervals </=20 msec. Changes in the extracellular calcium concentration altered the magnitude of the BDNF effect on PPF and synaptic responses to HFS, suggesting that BDNF regulates neurotransmitter release. When the desensitization of glutamate receptors was blocked by cyclothiazide or aniracetam, the BDNF potentiation of the synaptic responses to HFS was unaltered. Taken together, these results suggest that BDNF acts presynaptically. When two pathways in the same slice were monitored simultaneously, BDNF treatment potentiated the tetanized pathway without affecting the synaptic efficacy of the untetanized pathway. The selective potentiation of high-frequency transmission by BDNF appears to contribute directly to the effect of BDNF on LTP rather than indirectly by inducing the release of additional diffusible factors. The preferential potentiation of highly active synapses by BDNF may have implications in the Hebbian mechanism of synaptic plasticity.

Animals↗
PubMed1994

[Atypical symptoms in patients with germinal testicular tumors].

The cardinal syndrome of a testicular germ cell tumour is typically scrotal enlargement. The present paper compares the group of patients with typical scrotal presentation and those who present with atypical symptoms caused by metastases. Among 284 retrospectively studied patients, 34 (12%) presented with extrascrotal symptoms. The most important were abdominal pain (n = 16) and pulmonary symptoms (n = 10). The group of patients with extrascrotal symptoms was characterized by the following parameters: percentage of pure seminoma in 35% (versus 56% in the patients with typical presentation), elevation of alpha-feto-protein in 47% (versus 27%), and elevation of beta-HCG in 61% (versus 29%). The outcome was lethal in 35% of the patients with atypical presentation, as opposed to 6% of those with typical presentation. In 22 patients with extrascrotal presenting signs a palpable testicular mass was found on clinical examination. Occult testicular tumour proved to be present in 9 patients, and burned-out tumours in 3. Unawareness of testicular cancer is a significant factor in diagnostic delay. Scrotal palpation should be part of every clinical examination in younger male patients with cancer from an unknown primary.

Adult↗
PubMed1984

Cancer pain relief using chronic morphine infusion. Early experience with a programmable implanted drug pump.

Fourteen patients were implanted with drug pumps to provide chronic epidural or intrathecal morphine to relieve pain due to cancer. A new programmable pump was used in seven of the patients and a constant infusion device was used in the other seven patients. Results, judged by subjective pain reports (on a 0 to 10 scale), decrease in oral narcotics, and change in activity level, were excellent in eight patients, good in five patients, and poor in one patient. The programmable device has the obvious advantage of being able to vary dose according to patient need and requires less frequent refilling. Four programmable pump failures occurred, two requiring replacement.

Adult↗
PubMed1978

Effects of monitoring high-risk pregnancies and intrapartum FHR monitoring on perinates.

A protocol of chronic antepartum surveillance was initiated at the University of Illinois hospitals in 1973 to assess the impact on perinatal mortality. At the same time, a policy of unselected fetal heart rate (FHR) monitoring was initiated to judge the effect on the intrapartum stillbirth rate. The impact of both programs played a significant role in the decline of perinatal mortality rates for infants weighing more than 1 500 g, from 21.1/1 000 births in 1970--1971 to 14.4/1 000 births in the monitored years 1973 and 1974 (p less than 0.02).

Amniotic Fluid↗
PubMed1976

Interactions between carotid sinus mechanoreceptor and chemoreceptor reflex loops.

Our experiments were designed to evaluate the combined influence of the mechanoreceptor and chemoreceptor control loops on the cardiovascular and respiratory systems. Both carotid sinus areas were isolated by a complete blind sac preparation in chloralose anesthetized dogs in which a flow probe had been implanted previously on the ascending aorta. The following variables were continuously monitored: central aortic pressure, heart rate, cardiac output, vascular resistance of a hind limb, tidal volume, respiratory rate, and oxygen consumption. While one sinus was submitted to step changes of pressure, the opposite sinus was kept at constant mean pressure. In addition, one sinus was perfused with either oxygenated of deoxygenated blood at constant flow rate. These studies show a definite interaction between the control loops initiated by the carotid sinus mechanoreceptors and those initiated by the chemoreceptors. The influence of the chemoreceptors is most marked in the peripheral beds, where it shifts the whole response curve of the mechanoreceptor control loop upward. This response accounts for most of the upward shift of the pressure response curve. On the other hand, the mechanoreceptor loop affects the ventilation, but this effect is range dependent, being most marked for the low pressure perfusion of the carotid sinus.

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