Excitatory effects of ACTH on noradrenergic neurons of the locus coeruleus in the rat

Responses of presumed noradrenaline-containing neurons in locus coeruleus (LC) to iontophoretically applied ACTH were determined. The full sequence ACTH1-39 and the partial sequence ACTH1-24 were excitatory on the majority of neurons tested. The partial sequence ACTH27-39 was without effect on most neurons. The presence of ACTH-containing fibers in LC together with the present results may suggest a controlling influence of the peptide on the noradrenaline system.     

The action of piracetam on the electrical activity of the hippocampal slice preparation: A field potential analysis

The action of various doses of piracetam on the electrical responses of in vitro hippocampal slices from the rat was investigated. Piracetam increased dose dependently the amplitude of the population spike response of pyramidal neurons evoked by stimulation of the stratum radiatum. Piracetam began to affect the population spike at a dose of 100 μM and consistently increased it at a dose of 1 mM. The drug had a rapid onset of action and recovery was seen within a few minutes following its removal. The response of the pyramidal neurons to antidromic stimulation was not affected by piracetam at concentrations up to 50 mM. Also, neither the amplitude nor the slope of the dendritic response was changed by the drug. Piracetam also did not affect either posttetanic or long-term potentiation of synaptic potentials. These findings suggest that the drug does not act through depolarization of the pyramidal cells or potentiation of the synaptic processes located on their dendrites. The action of piracetam on the feedforward- and feedback-mediated inhibition of pyramidal cells by basket cells was investigated in several series of experiments. At concentrations of 1 and 10 mM, piracetam did not change either of the two types of inhibitory mechanisms. Several hypothetical sites of action of piracetam are discussed.     

The effects of baclofen and two GABAB-receptor antagonists on long-term potentiation

Summary The aim of the present study was to investigate whether activation or inhibition of GABA_B receptors in hippocampal slices of rats has an impact on the synaptic plasticity in the CA1 area. Long-term potentiation (LTP) was induced by tetanic stimulation of the Schaffer collateral/commissural fiber tract and the responses of CA1 pyramidal neurons were recorded extracellularly. The increase in population spike amplitude after tetanic stimulation was taken as a measure of LTP.The selective GABA_B receptor blockers phaclofen (1 mM) and CGP 35348 (100 M) facilitated the induction of LTP. Although baclofen (1 M) reduced the population spike amplitude, it did not affect LTP. If, however, the stimulation voltage was increased to compensate for the baclofen-induced decline in population spike amplitude, LTP was facilitated. Under these conditions the induction of LTP was accompanied by the appearance of additional population spikes.In conclusion, GABA_B receptors appear to exert a modulatory action on LTP.Send offprint requests to H. R. Olpe at the above address     

Kaposi's sarcoma and malignant lymphoma in AIDS

Summary A 48-year-old homosexual with contacts in different countries, including Haiti, presented with multiple pigmented or bluish nodules on both lower legs and upper arms. He had a history of secondary syphilis, hepatitis B and herpes zoster ophthalmicus. Biopsies of the skin tumors revealed a typical Kaposi's sarcoma of low grade malignancy. The endothelial origin of the tumor was indicated by the presence of specific endothelial organelles (Weibel-Palade bodies) in the cytoplasma of the tumor cells. Erythrocytophagocytosis was found in tumor cells within and without the vascular channels. Laboratory tests were compatible with the clinical diagnosis of an acquired immune deficiency syndrome (AIDS) with a helper: suppressor T-lymphocyte ratio of 0.28 and a cutaneous anergy. In the course of the illness tumors of the stomach and duodenum were detected. Histology showed a malignant non-Hodgkin lymphoma of high grade malignancy. Within weeks the patient died in a cachectic state. Autopsy revealed a Kaposi's sarcoma of the skin with metastases in the stomach and a wide-spread malignant lymphoma in the gastrointestinal tract, in several visceral organs and in many lymph nodes.     

Activation of the noradrenergic projection from locus coeruleus reduces the excitatory responses of anterior cingulate cortical neurones to substance P

The effects of activating the coeruleocortical pathway on responses of cingulate cortical cells to substance P was determined in the rat. The pathway was activated by means of small injections of glutamate, via a stereotaxically positioned cannula, directly into the locus coeruleus. Such injections greatly reduced the excitatory responses of cortical cells evoked by the iontophoretic application of substance P. Variation in the dorsal and lateral sites of injection suggested that the locus coeruleus was the important position for eliciting these effects. Depletion of cortical noradrenaline greatly reduced the ability of these injections to inhibit the substance P responses. Injections of glutamate into the locus coeruleus did not reduce cortical cell responses to acetylcholine. Parenteral administration of propranolol but not phenoxybenzamine blocked the effects of the glutamate injections on the substance P responses.These data support our previous suggestion that the central noradrenergic system may have a functional inhibitory effect on responsiveness to substance P in the cingulate cortex.     

A synthetic peptide encompassing the G5 antigenic region of the rabies virus induces high avidity but poorly neutralizing antibody in immunized animals

The immunization of goats with a synthetic peptide encompassing the G5 antigenic site of the rabies virus surface glycoprotein induces a strong humoral immune response in the absence of a carrier protein. The immunized animals mounted high antibody titers and showed a strong avidity maturation of the B cell immune response to both the G5-peptide and purified surface glycoprotein G. This antibody weakly neutralized rabies virus carrying the G5 epitope but failed to neutralize escape mutants carrying a single point mutation in this epitope. A putative T helper cell epitope, functional in the context of different caprine MHC haplotypes, was identified by structure analysis of the G5-peptide. This striking dichotomy between high titers and antibody of high avidity to the glycoprotein G and poor neutralizing activity strongly suggests that antibody binding assays such as ELISA cannot always reliably predict the neutralizing activity of sera as measured in functional assays.     

Repetitive TMS over the human oculomotor cortex: comparison of 1-Hz and theta burst stimulation

The aim of the study was to compare the effect duration of two different protocols of repetitive transcranial magnetic stimulation (rTMS) on saccade triggering. In four experiments, two regions (right frontal eye field (FEF) and vertex) were stimulated using a 1-Hz and a theta burst protocol (three 30Hz pulses repeated at intervals of 100ms). The same number of TMS pulses (600 pulses) was applied with stimulation strength of 80% of the resting motor threshold for hand muscles. Following stimulation the subjects repeatedly performed an oculomotor task using a modified overlap paradigm, and saccade latencies were measured over a period of 60min. The results show that both 1-Hz and theta burst stimulation had inhibitory effects on saccade triggering when applied over the FEF, but not over the vertex. One-hertz rTMS significantly increased saccade latencies over a period of about 8min. After theta burst rTMS, this effect lasted up to 30min. Furthermore, the decay of rTMS effects was protocol-specific: After 1-Hz stimulation, saccade latencies returned to a baseline level much faster than after theta burst stimulation. We speculate that these time course differences represent distinct physiological mechanisms of how TMS interacts with brain function.     

Orexin-A projections to the caudal medulla and orexin-induced c-Fos expression, food intake, and autonomic function

Orexin-expressing neurons in the hypothalamus project throughout the neuraxis and are involved in regulation of the sleep/wake cycle, food intake, and autonomic functions. Here we specifically analyze the anatomical organization of orexin projections to the dorsal vagal complex (DVC) and raphe pallidus and effects on ingestive behavior and autonomic functions of local orexin-A administration in nonanesthetized rats. Retrograde tracing experiments revealed that as many as 20% of hypothalamic orexin neurons project to the DVC, where they form straight varicose axon profiles, some of which are in close anatomical apposition with tyrosine hydroxylase (TH)-, glucagon-like peptide-1-, gamma-aminobutyric acid-, and nitric oxide synthase-immunoreactive neurons in a nonselective manner. Similar contacts were frequently observed with neurons of the nucleus of the solitary tract whose activation by gastrointestinal food stimuli was demonstrated by the expression of nuclear c-Fos immunoreactivity. Orexin-A administration to the fourth ventricle induced significant Fos-expression throughout the DVC compared with saline control injections, with about 20-25% of TH-ir neurons among the stimulated ones. Fourth ventricular orexin injections also significantly stimulated chow and water intake in nonfood-deprived rats. Direct bilateral injections of orexin into the DVC increased intake of palatable high-fat pellets. Orexin-ir fibers also innervated raphe pallidus. Fourth ventricular orexin-A (1 nmol) activated Fos expression in the raphe pallidus and C1/A1 catecholaminergic neurons in the ventral medulla and increased body temperature, heart rate, and locomotor activity. The results confirm that hypothalamomedullary orexin projections are involved in a variety of physiological functions, including ingestive behavior and sympathetic outflow.