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Biomedical subjects

H Hallman

Publications and source records attributed to H Hallman.

48 records · Page 3Linked to original sources
PubMed1979

Developmental plasticity of central noradrenaline neurons after neonatal damage--changes in transmitter functions.

The effects of neonatal 6-hydroxydopamine (6-OH-DA) treatment (systemic administration) on noradrenaline (NA) metabolism, turn over, and receptor characteristics have been investigated in rat brain in the adult stage. This treatment is known to preferentially affect the locus coeruleus (LC) NA system leading to a marked NA denervation in the central cortex and hyperinnervation of NA nerve terminals in the pons and medulla oblongata without influencing the LC perikarya. The main NA metabolite, 3-methoxy-4-hydroxy-phenylglycol (MOPEG) was reduced by about 70% in the cerebral cortex after 6-OH-DA treatment at birth while the endogenous NA was almost completely depleted (-92%). The MOPEG levels were not significantly changed in the pons medulla after 6-OH-DA treatment in contrast to the 60% increase of the endogenous NA concentration. The relative reduction of NA in the cerebral cortex of 6-OH-DA treated rats increased in the cerebral cortex following administration of the tyrosine hydroxylase inhibitor alpha-methyl-p-tyrosine (H44/68) compared to the control, while the H44/68 induced depletion of NA was reduced in the pons medulla after 6-OH-DA. The steady-state level of endogenous NA and the effect of H44/68 were unchanged in the LC perikarya after 6-OH-DA treatment. These results indicate that the NA turn over in remaining NA nerve terminals in the cerebral cortex is increased after 6-OH-DA, while decreased in the pons-medulla, possible related to changes in the activation of presynaptic alpha-adrenoreceptors in both regions. NA-induced formation of cAMP in vitro was found to be markedly increased in the cerebral cortex after 6-OH-DA, whereas no consistent change was observed in the pons medulla. Measurements of alpha- and beta-receptor binding in vitro using radioligand techniques showed an increase of binding sites (20%--50%) for both receptors in the neocortex aster 6-OH-DA, whereas no changes were observed in the pons medulla. The 6-OH-DA induced changes in NA turnover, cAMP generating systems, and receptor density may all represent compensatory processes following the altered development of the NA neurons induced by 6-OH-DA.

Aging↗
PubMed1979

Catecholamine turnover changes in hypothalamus and dorsal midline area of the caudal medulla oblongata of spontaneously hypertensive rats.

The central noradrenaline (NA) and adrenaline (A) turnover in 15--16-week-old stroke prone, spontaneously hypertensive (sp-SH) female rats in an advanced stage of hypertension was found to differ from that of normotensive Wistar-Kyoto (WKy) control rats. The catecholamine (CA) levels were measured after inhibition of dopamine-beta-hydroxylase (DBH) or phenylethanolamine-N-methyltransferase (PNMT). in the hypertensive rats the dopamine (DA) and NA levels and the NA turnover were reduced in the hypothalamus, while in the dorsal part of the caudal medulla oblongata NA levels and A turnover were reduced. Changes in hypothalamic DA and NA mechanisms and in A mechanisms in medulla oblongata may therefore be of importance in the blood pressure regulation of sp-SH rats.

Animals↗
PubMed1979

Catecholamines and hemorrhagic shock in awake and anesthetized rats.

Catecholamines in plasma and tissue were determined during hemorrhagic shock in the rat. Two groups of rats were compared. 1. Awake rats bled to 70 mm Hg for 4 hours. 2. Anesthetized rats (pentobarbital sodium 60 mg/kg) bled to 35 mm Hg for 4 hours. The mortality rate was similar in both groups. The bled volume was also similar. The awake rats responded with tachycardia upon bleeding while the anesthetized rats responded with bradycardia. The basal plasma levels of noradrenaline (NA), adrenaline (A) and dopamine (DA) in the awake rats were 2.87, 4.09, and 0.51 nmol/l respectively and in the anesthetized rats 0.97, 0.54, and 0.56 nmol/l respectively. At the onset of bleeding there was a more rapid increase of plasma A and NA in the awake rats than in the anesthetized rats. In the awake rats plasma A reached its peak value (70 nmol/l) at 1 hour and then decreased, while NA showed a slow continuous rise to 17 nmol/l at 4 hours. In the anesthetized rats plasma A remained at a high level (about 60 nmol/l) between 1 and 4 hours, while there was a continuous rise of NA to 17 nmol/l at 4 hours. In these rats a very high DA level (17 nmol/l) was also found at 4 hours. The tissue content of NA was not significantly decreased in the heart while a significant decrease was seen in the skeletal muscle after bleeding for 4 hours. In the heart there was a substantial increase of A after bleeding. The A content of the adrenals decreased to about 25% of the initial value in the awake animals. The results show that barbiturate anesthesia considerably depresses the initial sympatho-adrenal response to bleeding.

Adrenal Glands↗
PubMed1978

Developmental plasticity of central serotonin neurons after 5,7-dihydroxytryptamine treatment.

Systemic administration of 5,7-HT to newborn rats produces an altered development of the 5-HT neurons in the central nervous system, with marked regional differences. 5,7-Hydroxytryptamine can enter the brain and elicit its neurotoxic actions after systemic administration in the neonatal stage due to an incompletely developed blood-brain barrier, which for 5,7-HT is elaborated between postnatal Days 5 and 7. Treatment with 5,7-HT at birth produces marked and permanent 5-HT denervation in the cerebral cortex and spinal cord, whereas hyperinnervation occurs in the 5-HT cell body-near regions (mesencephalon-pons-medulla). The latter effect is seen within the first week postnatally. Treatment with 5,7-HT also affects NA neurons in a similar manner, although the action is exerted preferentially on 5-HT neurons. A selective effect on 5-HT neurons can be achieved by DMI pretreatment, after which both NA and DA neurons develop normally. No signs of any interaction among growing 5-HT, NA, and DA neurons can be observed. Studies of the postsynaptic 5-HT receptor in vitro with [3H]-5-HT and [3H]LSD binding indicate that this receptor develops independently of presynaptic 5-HT nerve terminals. Neither 5-HT denervation nor 5-HT hyperinnervation was accompanied by any change in receptor-binding characteristics or receptor density. The results available are compatible with the view that the consequences for 5-HT neurons that occur after neonatal 5,7-HT administration are mainly due to a "pruning effect." The developing 5-HT neurons seem to be programmed to produce a certain quantity of nerve terminal arborizations, which they try to conserve after 5-HT-induced injury, leading to the observed rearrangement of 5-HT nerve terminals.

5,7-Dihydroxytryptamine↗
PubMed1975

Microspectrofluorimetric analysis of the formaldehyde induced fluorescence in midbrain raphe neurons.

The formaldehyde induced fluorescence in perikarya localized in the midbrain rephe nuclei was investigated using the Falck-Hillarp technique in combination with qualitative (spectral analysis) and quantitative microspectorfluorimetry. The spectral evidence obtained after various pharmacological and lesion experiments with the neurotoxic compounds 5,6-dihydroxytryptamine and 5,7-dihydroxytryptamine, strongly favours the view that the vast majority of the perikarya in the cell groups B-7, B-8 and B-9 (according to Dahlström and Fuxe) are 5-hydroxytryptamine neurons, defined as structures capable of synthesizing, metabolizing, and storing 5-hydroxytryptamine. The spectral data indicate that the 5-hydroxytryptamine neurons might contain in addition to 5-hydroxytryptamine another indolealkylamine, possibly tryptamine, in low concentrations. The perikarya were shown to be able to take up and accumulate exogenously administered 6-hydroxytryptamine provided that monoamine oxidase was inhibited. Quantitative microfluorimetric analysis disclosed that the tryptophan hydroxylase inhibitor p-chlorophenylalanine was unable to block effectively this enzyme in the 5-hydroxytryptamine perikarya, although acutely a partial blockade was observed. The 5-hydroxytryptamineerogenously to the action of p-chlorophenylalanine and this might be associated with different states of neuronal activity. The difference in potency of p-chlorophenylalanine as regards tryptophan hydroxylase inhibition in perikarya and in nerve terminals may be related to different properties of tryptophan hydroxylase in various parts of the neuron and/or to a high turnover of the enzyme in the perikarya.

5-Hydroxytryptophan↗
PubMed1975

Quantitative microfluorimetry of formaldehyde induced fluorescence of dopamine in the caudate nucleus.

Quantitative microfluorimetric studies were carried out on the formaldehyde induced fluorescence of dopamine in nerve terminals of the nuc. caudatus putamen using the technique of Falck and Hillarp. After tyrosine hydroxylase inhibition produced by alpha-methyl-p-tyrosine (H 44/68) a time-dependent disappearance of the dopamine fluorescence occurred in an exponential manner, T1/22.6 hr. Apomorphine treatment resulted in a considerable counteraction of the H 44/68 induced reduction of the fluorescence, whereas treatment with haloperidol potentiated it. Administration of gamma-hydroxybutyrolactone led to a marked increase of the dopamine fluorescene. The present microfluorimetric results were in perfect agreement with chemical-analytical determinations of dopamine carried out under identical experimental conditions, and with those reported previously. The fluorescence intensities obtained in the nuc. caudatus putamen were found to be in the linear part of the dopamine fluorescence concentration relationship as observed in protein models. It may be concluded that by using microfluorimetric quantitation of the formaldehyde induced fluorescence in the nuc. caudatus putamen it is possible to obtain a reliable quantitation of the relative amount of dopamine in the dopamine nerve terminals.

Animals↗
PubMedDate not supplied

Immunohistochemical analysis of the effects of cysteamine on somatostatin-like immunoreactivity in the rat central nervous system.

The brain and spinal cord of untreated and cysteamine-treated rats were analyzed with immunohistochemistry using antisera raised against somatostatin (SOM)-28(1-14) and SOM-28(15-28). Sections incubated with increasing dilutions of antiserum were evaluated subjectively on coded slides and with computer-assisted image analysis. For control experiments, antisera raised against methionine-enkephalin, neuropeptide Y (NPY) and dynorphin (DYN)(1-13) were used. The latter antiserum does not visualize the conventional DYN systems in the brain, but reacts with an unknown epitope, which here could be shown to be present in SOM neurons. In cysteamine-treated rats a marked decrease in SOM-28(15-28)-like immunoreactivity (1.1) could be recorded subjectively at all antibody concentrations in fibers in several brain areas, including nucleus accumbens, tuberculum olfactorium and the hypothalamic ventromedial and arcuate nuclei. In these areas SOM-LI is fairly weak in untreated rats. In SOM-rich regions such as the median eminence and the dorsal horn of the spinal cord, the depleting effect of cysteamine could be recorded subjectively only when diluted antisera were used. Image analysis confirmed the subjective analysis, and, in addition, differences between controls and cysteamine-treated rats could be shown also at high antiserum concentrations. SOM-28(15-28)-immunoreactive cell bodies could be seen in the brains of either control or drug-treated rats. No effect of cysteamine could be observed when antiserum raised to SOM-28(1-14) was used. Cysteamine did not seem to affect enkephalin-LI, NPY-LI or an epitope in SOM neurons reacting with DYN(1-13) antiserum. After preabsorption of SOM-28(15-28) antiserum with SOM-28(15-28) peptide, the staining patterns described above disappeared completely. However, if the SOM-28(15-28) peptide was pretreated with a high concentration (1 M) of cysteamine before being used for absorption with SOM antiserum, no blocking effect could be observed. The present results demonstrate with immunohistochemistry that cysteamine causes depletion of SOM-28(15-28) in fibers but apparently not in cell bodies. No effects on SOM-28(1-14)-LI were observed. This supports earlier evidence that cysteamine interacts with the disulphide bond in the SOM-28(15-28) molecule. The present results also emphasize that when analyzing drug effects on peptide neurons with immunohistochemical techniques, it is important to use dilution series of antibodies and preferably to carry out the analysis with objective image analysis methods.

Animals↗
PubMedDate not supplied

Modulation of 6-hydroxydopamine induced alteration of the postnatal development of central noradrenaline neurons.

The effect of substance P and morphine on the 6-hydroxydopamine (6-OHDA) induced alteration of the postnatal development of central noradrenaline (NA) neurons in the rat has been investigated using neurochemical techniques. Neonatal administration of 6-OHDA systemically leads to permanent NA denervations of distant NA projections, while the projections close to the NA cell bodies are increased, leading to NA hyperinnervation. Intracisternal injection of substance P was found to counteract both the NA denervation and hyperinnervation induced by 6-OHDA. The effect of substance P disclosed a clear dose-dependent relationship. Morphine, on the other hand, was observed to potentiate the alterations induced by 6-OHDA, both the NA denervation and hyperinnervation. The effect of morphine was dose-dependent and could be blocked by the morphine antagonist naloxone. The present results give further support for the view that the 6-OHDA induced alteration of the postnatal development of central NA neurons is related to a "pruning effect." The data furthermore imply that the end-result from a 6-OHDA induced degeneration of central NA neurons during ontogeny may be modulated by the functional state of the neurons.

Animals↗
PubMedDate not supplied

Autoradiographic mapping of galanin receptors in the monkey brain.

The distribution of specific binding sites for the peptide galanin was studied in the monkey brain by using 125I-galanin and the method of quantitative in vitro autoradiography. The binding to tissue sections was found to be rapid, reversible and saturable with a calculated Bmax of around 13 fmol mg-1 tissue in cortical regions and a KD ranging between 0.39 and 0.22 nM in different brain regions. Specifically bound 125I-galanin was detected in a number of brain regions throughout the rostrocaudal axis of the monkey brain. More specifically, the majority of the 125I-galanin binding sites were present in the basal forebrain (e.g. olfactory tubercle, lateral septal nuclei, nucleus accumbens, substantia innominata and the basal nucleus of Meynert), the amygdala (e.g. the lateral, medial accessory and central nuclei), the amygdala-hippocampal area, hypothalamus (e.g. the anterior hypothalamic area, the ventro-medial hypothalamus and the zona incerta), as well as in certain brain stem cell groups such as the substantia nigra (pars compacta), locus coeruleus, central grey substance, parabrachial nucleus, sensory and motor nuclei of the trigeminal nerve and the dorsal vagal complex. In the neocortex, highest binding density occurred in layer 4 of all neocortical fields, except in the visual cortex where the highest densities occurred in layers 4cb, 5a and 6. Major fibre tracts such as the fimbria and the stria terminalis also contained high densities of 125I-galanin binding sites. Areas poor in, or lacking, specific 125I-galanin binding sites included the basal ganglia, the thalamus, the mammillary bodies, the cerebellum, and the reticular formation of the brain stem. The pattern of galanin receptor distribution in the monkey brain reported here closely resembles that observed for galanin receptors and galanin-immunoreactive preterminal processes described previously in the rat brain. An exception, however, was neocortex, where in the rat neither 125I-galanin binding nor galanin-positive fibres have been observed. The present findings may indicate a close association between galanin receptors and nerve terminals containing galanin immunoreactivity in the monkey brain and implies important role(s) for galanin in neurotransmission in the monkey central nervous system.

Animals↗