Search PubMed⌕ Search

Biomedical subjects

G Jonsson

Publications and source records attributed to G Jonsson.

At least 91 records · Page 5Linked to original sources
PubMed1985

Complete blockade and attenuation of 5-hydroxytryptamine induced analgesia following NA depletion in rats and mice.

The effect of pretreatment with the noradrenaline neurotoxin, N-2-chloroethyl-N-ethyl-2-bromobenzylamine (DSP4), upon the analgesia induced by various doses of 5-hydroxytryptamine (5-HT) was examined in rats and mice. DSP4 treatment (2 X 50 mg/kg, intraperitoneally) of rats caused a complete blockade of 5-HT induced analgesia in the tail-flick, hot-plate and shock titration tests. DSP4 treatment (1 X 50 mg/kg, intraperitoneally) of mice caused a partial blockade of 5-HT induced analgesia in the hot-plate test, but no significant blockade in the tail-flick test. These results are discussed with regard to serotonergic-noradrenergic interactions and the species discrepancy in nociceptive testing.

Analgesics↗
PubMed1985

Flexor tenosynovitis (FTS): a risk indicator of abnormal glucose tolerance.

Diabetes mellitus (DM), particularly of long duration and insulin dependent, can be accompanied by a variety of locomotor system disorders. However, musculo-skeletal syndromes can also appear in patients with mild glucose homeostasis disturbances. Sometimes these locomotor complaints may precede the diagnosis of the deranged glucose metabolism and hence give a clue to the underlying glucose homeostasis abnormality. In the present work, glucose metabolism was studied in 39 patients presenting with palmar flexor tenosynovitis (FTS) but without any other rheumatic manifestations. For comparison, glucose homeostasis was also studied in 44 patients with FTS accompanying rheumatoid arthritis (RA). In the first group, 23% had an abnormal oral glucose tolerance test (OGTT), a significantly increased frequency vis-à-vis the 4.5% found in the RA group and vis-à-vis the 5.4% reported for the general population. It is concluded that in the absence of any other rheumatic disease, FTS is a risk indicator of disturbed glucose metabolism and that a simple screening procedure for the purpose of disclosing glucose homeostasis abnormalities is warranted in patients presenting with FTS.

Adult↗
PubMed1985

Dopaminergic neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the mouse: an in vivo electrochemical study.

The long-term (i.e., 4-5 months) effects of large doses (3 X 50 mg/kg) of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on striatal dopamine-containing afferents were studied in the NMRI strain of mice. Recently improved in vivo electrochemical methods were first used to examine the magnitude, spatial distribution and temporal dynamics of monoamine release initiated via local application of potassium in various regions of the mouse striatum. Immunohistochemical localization of tyrosine hydroxylase and computer-based image analysis were also used to quantitate regional catecholamine-containing nerve fiber densities in the caudate nucleus. The in vivo electrochemical studies showed a statistically significant decrease in the average potassium-evoked release of electroactive species from the MPTP-treated mouse caudate nucleus vs. control. Greater decreases in release were seen in dorsal than in ventral striatum (55% vs. 33%). The average rise time of potassium-evoked release was also significantly prolonged (greater than 50%) after MPTP pretreatment. Histochemical studies showed an overall reduction in the density of dopamine-containing terminals in the drug-treated mice, with a greater loss observed in the more dorsal regions of the caudate nucleus. The experimental data thus support a long-term selective destruction of dorsal vs. ventral dopamine-containing afferents to the striatum by the neurotoxin MPTP in mice.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1984

Pharmacological modifications of the neurotoxic action of the noradrenaline neurotoxin DSP4 on central noradrenaline neurons.

Systemic treatment with the noradrenaline neurotoxin DSP4 (N-[2-chloroethyl]-N-ethyl-2-bromobenzylamine; 7 days) led to a marked and quantitatively similar reduction (-80%) of endogenous noradrenaline, [3H]noradrenaline uptake in vitro and [3H]desipramine binding in the frontal cortex of adult rats. Inhibition of monoamine oxidase, and/or 1-dopa administration 1 week after DSP4 produced very small changes in brain noradrenaline and dopamine levels. These results are all consistent with the view that DSP4 produces an acute and selective degeneration of central noradrenaline nerve terminals. Pretreatment with the noradrenaline uptake blocker desipramine prevented the action of DSP4 almost completely, while treatment after DSP4 had minute effects on DSP4-induced reduction of endogenous noradrenaline and [3H]noradrenaline uptake. The data suggest that the irreversible neurotoxic actions of DSP4 are very rapid and largely complete within 0.5 h after DSP4 administration. Measurement of catecholamine turnover using monoamine oxidase inhibition by pargyline indicated an increased noradrenaline turnover in the remaining nerve terminals innervating cerebral cortex and hippocampus after DSP4, while dopamine turnover appeared to be decreased. Pretreatment with d-amphetamine and clonidine or subsequent treatment with oxotremorine were without effect on the DSP4-induced reductions of the regional brain noradrenaline levels. Morphine pretreatment was also ineffective, while repeated morphine administration after DSP4 produced a significant potentiation of the DSP4-induced noradrenaline depletion in the frontal cortex, cerebellum and the spinal cord. Pretreatment with the monoamine oxidase inhibitor pargyline led to a very pronounced counteraction of the DSP4-induced noradrenaline depletion in all brain regions analysed, in particular in the occipital cortex. The data suggest that morphine can potentiate the neurotoxic action of DSP4 while pargyline can counteract it.

Amines↗
PubMed1984

Neurotoxicity of the meperidine analogue N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine on brain catecholamine neurons in the mouse.

The effect of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (NMPTP) on central monoamine neurons in mice was investigated using histo- and biochemical techniques. NMPTP (2 X 10 mg/kg i.v.) produced a rapid and long-lasting reduction (-30%) of striatal dopamine, while the dopamine levels were only transiently reduced in mesencephalon and frontal cortex. HVA and DOPAC were initially markedly reduced (-50 to -70%) in striatum while a marked recovery was found in the chronic stage. NMPTP also induced a long-term reduction of noradrenaline in striatum and frontal cortex while 5-hydroxytryptamine and 5-HIAA levels were essentially unaltered. The data indicate a neurotoxic action of NMPTP on both dopamine and noradrenaline nerve terminals in mouse brain.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1984

Effects of GM1 ganglioside on developing and mature serotonin and noradrenaline neurons lesioned by selective neurotoxins.

The effect of exogenous GM1 ganglioside on selective neurotoxin-induced lesions of serotonin (5-HT) and noradrenaline (NA) neurons in both the central and peripheral nervous systems has been investigated in developing and adult rats and mice by employing neuro- and histochemical techniques. 5,7-Dihydroxytryptamine (5,7-HT) was used to lesion 5-HT neurons, and 6-hydroxydopamine (6-OH-DA) was used to lesion NA neurons. In most lesion models investigated the neurotoxin causes primarily an axonal nerve terminal damage without notably affecting the perikarya. There was no evidence indicating that GM1 interferes with the primary and direct neurodegenerative actions of 5,7-HT or 6-OH-DA on 5-HT and NA nerve terminals, respectively. In all lesion models GM1 had in the chronic stage a counteracting effect on the neurotoxin-induced nerve terminal lesion or enhanced regrowth. The present results are compatible with the view that GM1 has a regrowth-stimulating effect and/or protective actions against secondary retrograde degeneration following the initial nerve terminal lesion induced by the neurotoxin.

5,7-Dihydroxytryptamine↗
PubMed1984

Effects of the noradrenaline neurotoxin DSP 4 on monoamine neurons and their transmitter turnover in rat CNS.

Regional effects of DSP 4 on monoamine neurons have been analyzed by chemical assay of endogenous monoamines and their metabolites in rat CNS. The results confirmed that the neurotoxic action of DSP 4 is predominantly on noradrenaline nerve terminal projections originating from locus coeruleus, with the most marked effects on terminal fields localized most distant from the noradrenaline perikarya. DSP 4 treatment (10 days) caused no alteration of the regional DA levels, except in cingulate cortex, where a moderate increase (+40%) was observed, possibly at least partially related to a sprouting of dopamine nerve terminals following the noradrenaline denervation. 5-hydroxytryptamine levels were generally unaltered after DSP 4, except for an about 10-25% reduction in cerebral cortex and hippocampus. There was with time a certain noradrenaline recovery, most likely related to regeneration of noradrenaline nerve terminals, although this process was relatively slow (months). Analysis of catecholamine decline after tyrosine hydroxylase inhibition and metabolite/monoamine ratios, as indices for transmitter utilization rate, indicated an increased noradrenaline turnover in terminals spared by DSP 4, while dopamine turnover appeared to be reduced in many regions (i.a. cerebral cortex, striatum, accumbens, olfactory tubercle and spinal cord), most pronounced in cingulate cortex. The results indicate that noradrenaline neurons have a facilitatory action on dopamine neurons. The DSP 4 treatment did not cause any significant effect on 5-hydroxytryptamine turnover in any of the individual regions analyzed.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1984

Measurement of 5-hydroxytryptophol and 5-hydroxyindoleacetic acid in human and rat brain and plasma.

The levels of 5-hydroxyindoleacetic acid (5-HIAA) and free and total 5-hydroxytryptophol (5-HTOL) in human and rat brain regions and plasma were determined by a specific capillary column gas chromatographic--mass spectrometric method. The human brains were obtained 2-3 hours post mortem, and the levels of 5-HIAA were in the range of 0.48-31.3 nmoles/g in the regions investigated. The levels of free and total 5-HTOL were 10.9-387 pmoles/g and 14.5-821 pmoles/g, respectively. The ratio of total 5-HTOL to 5-HIAA was in the range of 0.6-5.5%. In human plasma the levels of free and total 5-HTOL were 0.9 +/- 0.3 and 2.9 +/- 0.8 pmoles/ml +/- S.E.M., respectively. In regions of rat brain, the 5-HIAA levels ranged from 0.37-2.84 nmoles/g. Free and total 5-HTOL were in the range of 11.4-56.1 and 16.2-77.1 pmoles/g, respectively. The ratio of total 5-HTOL and 5-HIAA ranged from 2.3-5.1%. Higher levels of 5-HIAA and 5-HTOL occurred in the rat pineal gland. In rat plasma the levels of free and total 5-HTOL were 1.34 +/- 0.06 and 21.6 +/- 1.6 pmoles/ml +/- S.E.M., respectively.

Aged↗
PubMed1984

Effect of GM1 ganglioside on neonatally neurotoxin induced degeneration of serotonin neurons in the rat brain.

The effect of exogenous GM1 ganglioside on the 5,7-dihydroxytryptamine (5,7-HT; a selective serotonin neurotoxin) induced alteration of the postnatal development of central 5-hydroxytryptamine (5-HT; serotonin) neurons has been investigated using neuro-chemical and immunocytochemical techniques. Neonatal 5,7-HT (50 mg/kg s.c.) treatment is known to lead to a marked and a permanent degeneration of distant 5-HT nerve terminal projections (e.g. in cerebral cortex, hippocampus and spinal cord), while projections close to the 5-HT perikarya in the mesencephalon and pons-medulla increase their nerve density. These regional alterations are reflected by decreases and increases, respectively, of endogenous 5-HT, [3H]5-HT uptake in vitro and number of 5-HT nerve terminals demonstrated by immunocytochemistry. Treatment of newborn rats with GM1 (4 X 30 mg/kg s.c.; 24 h interval) had no significant effect on the postnatal development of 5-HT neurons. GM1 administration had furthermore no effect on the 5,7-HT induced alteration of the regional 5-HT levels and [3H]5-HT uptake in the cerebral cortex acutely, indicating that GM1 did not significantly interfere with the primary neurodegenerative actions of 5,7-HT. At the age of 1 month a clear counteracting effect of GM1 was observed, in particular of the 5,7-HT induced 5-HT denervations. The 5-HT levels in the frontal and occipital cortex were reduced to 25 and 20% of control after 5,7-HT alone, while these values were 70 and 40%, respectively, after 5,7-HT and GM1 treatment. A similar antagonizing effect of GM1 was found in the frontal cortex when measuring [3H]5-HT uptake. GM1 treatment also caused a minor reduction of the 5,7-HT induced increase of the 5-HT levels in striatum and mesencephalon. Quantitation of 5-HT nerve terminal density in sections processed for 5-HT immunocytochemistry using an automatic image analysis system showed markedly more nerve terminals in the frontal and occipital cortex after 5,7-HT + GM1 compared to 5,7-HT treatment alone. Minor counteracting effects of GM1 were noted in the hippocampus and spinal cord (thoracic-lumbar) as evaluated by chemical 5-HT assay, although substantial counteracting effects were observed locally in these areas by quantitative immunocytochemistry.(ABSTRACT TRUNCATED AT 400 WORDS)

5,7-Dihydroxytryptamine↗
PubMed1984

GM1 ganglioside enhances regrowth of noradrenaline nerve terminals in rat cerebral cortex lesioned by the neurotoxin 6-hydroxydopamine.

The effect of exogenous GM1 ganglioside on selectively noradrenaline-denervated rat cerebral cortex was investigated by measuring the spatial distribution of endogenous noradrenaline levels and by fluorescence histochemical analysis. A local noradrenaline denervation was produced by intracortical infusion of the selective catecholamine neurotoxin 6-hydroxydopamine for 3 or 7 days. The neurotoxin infusion caused an almost complete noradrenaline denervation in a restricted area around the infusion point as reflected by an almost complete long-term disappearance of noradrenaline nerve terminals and reduction of noradrenaline levels. There was with time a slow recovery of the levels, most likely related to a spontaneous noradrenaline nerve terminal regeneration. Post-treatment for 1 week with GM1 had very small effects on the 6-hydroxydopamine-induced reduction of the noradrenaline levels, while pretreatment with GM1 for 3 days before the neurotoxin infusion and continuing the GM1 administration for another 7-14 days significantly enhanced noradrenaline recovery, as observed both bio- and histochemically. GM1 had no effect on the 6-hydroxydopamine-induced noradrenaline depletion acutely, indicating that GM1 does not interfere with the direct neurotoxic actions of 6-hydroxydopamine. The present results thus indicate that exogenous GM1 enhances regrowth of noradrenaline nerve terminals which may be due to a regrowth stimulatory effect (regeneration/collateral sprouting) and/or related to protective actions of GM1 against retrograde degeneration of noradrenaline axons following the neurotoxin-induced lesion.

Adrenergic Fibers↗
PubMed1984

Monoamine neurotransmitter metabolism in microencephalic rat brain after prenatal methylazoxymethanol treatment.

Administration of methylazoxymethanol (MAM) in the fetal stage leads to forebrain microencephaly with a severe atrophy in cerebral cortex, striatum, and hippocampus. The concentration of endogenous monoamines was markedly increased in the atrophic regions while total amount was largely unchanged. Striatal dopamine and cortical noradrenaline nerve terminals from MAM treated animals showed unaltered sedimentation properties in a sucrose density gradient and were estimated to have normal transmitter levels. gamma-Butyrolactone induced increase in dopamine levels and its counteraction by apomorphine was essentially unaltered after MAM. These data give further support for the view that the monoamine nerve terminal fields develop to their normal size in the atrophic regions leading to a hyperinnervation. Analysis of monoamine metabolite levels, increase of monoamines after monoamine oxidase inhibition, and disappearance of catecholamines after tyrosine hydroxylase inhibition were conducted to obtain information on monoamine turnover. The results indicated an essentially unaltered, or a small reduction of, monoamine turnover in the atrophic regions when calculated per monoamine nerve terminal, while increased when calculated per unit weight of the tissue.

Abnormalities, Drug-Induced↗
PubMed1984

Role of olfactory bulbectomy and DSP4 treatment in avoidance learning in the rat.

Olfactory bulbectomized rats and DSP4-treated rats were studied on a two-way active avoidance task as well as on step-down passive avoidance and fear conditioning and retention tasks in three experiments. The DSP4-treated, but not olfactory bulbectomized, rats were impaired in acquiring two-way avoidance; bulbectomized, but not DSP4-treated, rats were found to show notable passive avoidance and fear retention deficits. Bulbectomized rats treated with DSP4 did not show passive avoidance and fear retention deficits, nor did these animals evidence the two-way avoidance impairment of the DSP4-treated rats. No alteration of dopamine-beta-hydroxylase activity in the frontal cortex and hippocampus as a result of the bulbectomy operation was indicated. The double dissociation between bulbectomized and DSP4-treated rats is discussed in terms of opponent behavioral processes, influenced by olfactory bulbectomy and DSP4, which may permit insights into experimental investigations of stress, anxiety, and depression.

Amines↗
PubMed1984

A parametric study of the effects of the noradrenaline neurotoxin DSP4 on avoidance acquisition and noradrenaline neurones in the CNS of the rat.

The effects of various doses of DSP4 on two-way active avoidance acquisition in rats and on central noradrenaline neurones were compared. Doses of DSP4 from 3 mg kg-1 i.p. and upwards injected one week before the onset of the avoidance trials significantly impaired two-way avoidance learning. The learning impairment caused by DSP4 (50 mg kg-1 i.p.) lasted for at least 10 weeks. Desipramine (20 mg kg-1) injected either 30 or 60 min before DSP4 (50 mg kg-1) antagonized the active avoidance impairment. A high dose of DSP4 (50 mg kg-1 i.p.) produced profound decreases in dopamine-beta-hydroxylase activity in the frontal cortex and in the concentrations of noradrenaline in various brain regions indicating degeneration of the locus coeruleus noradrenaline system. Low doses of DSP4 (3 and 6 mg kg-1 i.p.) produced small but significant decrease in the concentrations of noradrenaline (NA) in some regions, e.g. cerebral cortex, hippocampus, olfactory bulb and spinal cord. The avoidance impairment caused by the low dose of DSP4 (3 mg kg-1) was absent when rats were tested 10 weeks after treatment nor was NA depletion present when NA was analysed 3 months after treatment.

Amines↗
PubMed1984

Neurochemical studies on central dopamine neurons--regional characterization of dopamine turnover.

A simple and rapid dissection procedure was adopted to sample representative areas of the main meso-telencephalic dopaminergic (DA) neuron systems (nigrostriatal and meso-limbic-cortical) in the rat CNS. The object was to explore nerve terminal fields, cell body groups and dendrites, and to investigate the DA utilization rates in these regions. DA and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) as well as noradrenaline (NA) were determined by liquid chromatography with electrochemical detection. Selective NA denervation with the neurotoxin DSP4 did not significantly change the DA levels in any of the regions studied, showing that the main part of the DA analysed originated from DA neurons. Administration of the tyrosine hydroxylase inhibitor alpha-methyl-p-tyrosine (H44/68) resulted in a time-dependent, often multi-phasic, DA and NA depletion pattern that varied between different regions. Comparison between the rate of DA decline and DOPAC/DA or HVA/DA ratios (also indices for DA utilization) in the various regions showed that the initial rate of DA disappearance after H44/68 appeared to be the most relevant index of DA utilization. The most rapid initial DA decline after H44/68 was found in the cortical regions (frontal, cingulate, and entorhinal) and the cell body areas A9 and A10, in particular in the cingulate cortex (t1/2 approximately equal to 20 min), indicating a very rapid DA turnover in this region. DA disappearance was clearly slower in striatum (t1/2 approximately equal to 45 min) and the slowest rates were found in the olfactory tubercle and the nucleus accumbens (t1/2 approximately equal to 1.5-2 h). The DA disappearance (t1/2 approximately equal to 45 min) pattern in the dendritic area (substantia nigra, pars reticulata) suggested an axon-terminal like behaviour of the DA dendrites with respect to DA utilization. In general, the DA metabolite/DA ratios obtained for the various regions agreed closely with these results. The rate of NA disappearance after H44/68 was slower than that of DA in most regions. The most rapid NA decline was found in the cortical regions (t1/2 approximately equal to 1-2 h), while very slow in the A9 and A10 regions (t1/2 approximately equal to 3-5 h).

3,4-Dihydroxyphenylacetic Acid↗
PubMed1983

Maturation of monoamine neurotransmitters and receptors in cat occipital cortex during postnatal critical period.

The postnatal development of monoamine levels and receptors in the occipital cortex of the cat has been investigated using neurochemical techniques. The endogenous catecholamines (noradrenaline and dopamine) gradually increased with age, displaying an about 12-13-fold increase in their concentration from the newborn to the adult stage. 3H-dihydroalprendol (beta-adrenoceptor ligand) binding showed a rapid increase from the low value (25% of the adult value) at birth, peaking at the age of 7-9 weeks with a value of about 150% of adults. The beta-adrenoceptor binding stayed relatively constant at adult value from the age of 11 weeks throughout. Endogenous 5-hydroxytryptamine levels were at birth about 20% of the adult value and thereafter rapidly increased, peaking at the age of 3-5 weeks when it reached the adult value. Between the age of 7-13 weeks the 5-hydroxytryptamine level was about 50-60% of adult. The developmental pattern for 3H-5-hydroxytryptamine binding was similar to that of endogenous 5-hydroxytryptamine, although with certain quantitative differences. The 3H-5-hydroxytryptamine receptor binding showed a steep peak at an age of about 4 weeks when the binding was about 300% of the adult value. Thereafter the binding gradually levelled off in adulthood. Similar results were obtained in the frontal cortex, except for some quantitative differences. The present results thus indicate that both noradrenaline and 5-hydroxytryptamine nerve terminals develop, largely independent of their postsynaptic receptors, probably due to different developmental programs regulating their expression. The development of monoamine receptors appear to precede that of their nerve terminals. The different roles played by beta-adrenoceptors and 5-hydroxytryptamine receptors for the maturation of occipital cortex during postnatal critical period were discussed.

Animals↗
PubMed1983

Immunohistochemical and neurochemical evidence for the presence of serotonin in the adrenal medulla of the rat.

Immunohistochemical and biochemical techniques were used to look for serotonin in the adrenal medulla of the rat. Using antibodies to serotonin, noradrenaline and adrenaline, it could be shown that the adrenaline-storing cells are highly immunoreactive for serotonin. Noradrenaline-storing cells were not stained even after administration of the precursors L-tryptophan and 5-hydroxytryptophan, or of serotonin itself. Specificity of the immune reaction was studied by both absorption and inhibition experiments. Chemical assays showed that rat adrenals contain significant amounts of serotonin (1.4 +/- 0.11 micrograms/g wet weight) which is about 0.4% of the adrenaline levels. Serotonin could be reduced to about 10% of control by a high dose of reserpine. From differential and sucrose gradient centrifugation experiments it was concluded that serotonin is probably stored in granules also containing adrenaline. Administration of 5-hydroxytryptophan led to a marked increase of the serotonin level, preferentially in the granular fraction. This increase could be blocked almost completely by a decarboxylase inhibitor. Serotonin administration did not result in a statistically significant increase of the serotonin concentration. Serotonin levels were not changed either after administration of L-tryptophan or the tryptophan hydroxylase inhibitor H22/54. These results indicate that there is no significant synthesis of serotonin from L-tryptophan. It is suggested that the serotonin present in the adrenaline-storing cells is derived from circulating serotonin and/or 5-hydroxytryptophan. Serotonin taken up directly from the circulation or formed by decarboxylation from 5-hydroxytryptophan is subsequently incorporated in the chromaffin granules.

Adrenal Medulla↗