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Biomedical subjects

G Jonsson

Publications and source records attributed to G Jonsson.

At least 163 records · Page 9Linked to original sources
PubMed1976

Regional changes in [3H]-noradrenaline uptake, catecholamines and catecholamine synthetic and catabolic enzymes in rat brain following neonatal 6-hydroxydopamine treatment.

6-Hydroxydopamine (6-OH-DA) treatment of rats at birth (with the analyses conducted in the adult stage) produced marked regional variations in changes in endogenous noradrenaline (NA) and [3H]NA uptake in the CNS. The most pronounced reductions were seen in the cerebral cortex, hippocampus and the spinal cord. Moderate changes or none at all were seen in the hypothalamus, septum and thalamus. Marked increases in endogenous NA and [3H]NA uptake were seen in the mesencephalon and the pons-medulla oblongata. There was in general a close correlation between the changes in endogenous NA and [3H]NA uptake. The results from the cerebellum varied, depending on the developmental stage at which the 6-OH-DA treatment was performed. 6-OH-DA treatment up to three days after birth generally led to a marked increase in both endogenous NA and [3H]NA uptake, while continuing the treatment caused a marked reduction of both parameters. The 6-OH-DA treatment caused no changes in endogenous dopamine (DA) in all regions analysed. Enzyme activity assays showed that DA-beta-hydroxylase (DBH) and tyrosine hydroxylase (TH) were greatly reduced in the cerebral cortex, while the activity of both enzymes was almost double in the pons-medulla. No changes in the activity of phenylethanol-amine N-methyltransferase (PNMT), DOPA decarboxylase, COMT and MAO were seen after 6-OH-DA at birth. Measurements of choline acetyltransferase activity displayed only minute changes. The present results strongly support the view that 6-OH-DA treatment in the neonate stage produces a very selective action on NA neurones belonging to the locus coeruleus system from a structural standpoint, leaving DA- and PNMT-containing neurones unaffected. [3H]NA uptake in whole CNS was almost unchanged, despite the marked regional variations. The results have been interpreted as being due to a 'pruning effect', where the permanent NA denervation in distant nerve terminal projections (e.g. cerebral cortex) leads to a compensatory sprouting and increased outgrowth of NA terminal projections in areas close to the perikarya (e.g. pons-medulla). Furthermore, the results support the view that the growing locus coeruleus neurones are strictly programmed to produce a certain quantity of nerve terminal volume and arborization during the postnatal development.

Age Factors↗
PubMed1975

Effects of 6-hydroxydopamine on central noradrenaline neurons during ontogeny.

The effects of the catecholamine neurotoxic compound, 6-hydroxydopamine (6-OHDA) have been investigated on central noradrenaline (NA) neurons after neonatal administration. In agreement with previous studies this treatment (1-3 X 100 mg/kg) led to a pronounced reduction of the in vitro uptake of [3H]NA and the endogenous NA in the cerebral cortex, while these parameters were markedly augmented in the pons and medulla oblongata, regions containing the NA perikarya. The 6-OHDA induced changes in the cerebral cortex and the pons-medulla could be completely prevented by the 'membrane pump' blocker desipramine, indicating that the effects are associated with a specific neurotoxic action of 6-OHDA on the NA neurons. Consistently, 6-OHDA acutely (within 2 h) produced a marked reduction of the [3H]NA uptake in both the cerebral cortex and pons-medulla. In the cerebral cortex the nadir (approximately 75% reduction) was reached within 6 h and remained so, while in the pons-medulla the [3H]NA uptake rapidly recovered, being maximally elevated after 14 days (50-80% increase) and remained so for at least 6 months. The [3H]NA uptake in the pons-medulla from 6-OHDA treated rats had the same kinetic and pharmacological properties as that of control. Thus the observed differences in [3H]NA uptake are most likely quantitatively related to actual changes in the number of NA nerve terminals. Treatment with lower 6-OHDA doses (10 or 50 mg/kg) resulted in less pronounced reduction of [3H]NA uptake initially, and there was a gradual recovery of tuptake with time in the cerebral cortex, which was more pronounced after the lower dose. These results are indications of regenerative growth, which may be possible when a critical part of the axon is spared from the neurotoxic effect of 6-OHDA. Administration of 6-OHDA on various days after birth disclosed that both the reduction of [3H]NA uptake in the cerebral cortex and the increase of [3H]NA uptake in the pons-medulla did not appear as permanent phenomena when 6-OHDA was given later than on the seventh postnatal day. This is most likely associated with the postnatal development of the blood-brain barrier. It may be concluded that the neonatal 6-OHDA treatment causes a marked NA denervation in the forebrain, e.g. the cerebral cortex, and an increased outgrowth of NA nerve terminals in the pons-medulla, which is preceded by a partial damage. This partial NA denervation is then followed by a regeneration (regenerative and/or collateral sprouting) and a stimulated outgrowth of NA nerve terminals.

Animals↗
PubMed1975

Role of monoamines in the control by hormones of sexual receptivity in the female rat.

The involvement of indole- and catecholamines in the hormonal regulation of sexual receptivity has been investigated in ovariectomized female rats. Drugs that reduce 5-hydroxytryptamine, dopamine, and adrenaline or increase noradrenaline neurotransmission tended to facilitate the occurrence of estrous behavior in estrogen-treated females, and drugs having opposite effects tended to inhibit receptivity induced by estrogen and progesterone. Estrogen decreased noradrenaline turnover in cortex and brain stem; progesterone enhanced this effect in brain stem but prevented it in cortex. Both hormones tended to block noradrenaline uptake in hypothalamus in vitro. In a schedule used to induce receptivity, estrogen accelerated serotonin turnover, an effect prevented by progesterone. Thus a number of monoamines may be involved in the control by hormones of estrous behavior. Furthermore, hormones affect both amine turnover and uptake mechanisms.

Adrenalectomy↗
PubMed1975

Control of the neurotoxicity of 6-hydroxydopamine by intraneuronal noradrenaline in rat iris.

In vitro studies with the neurotoxic compounds 6-hydroxydopamine (6-OH-DA) and 6-aminodopamine (6-A-DA) showed that noradrenaline (NA) markedly inhibited the autooxidation of 6-OH-DA, but not of 6-A-DA. In vivo studies of the adrenergic nerves in rat iris showed that the neurotoxic potency of 6-OH-DA, but not 6-A-DA, was increased after NA depletion by alpha-methyl-p-tyrosine methylester (H44/68). Neurotoxicity was evaluated by measuring the associated decrease in 3-H-NA uptake. Intraocular injection of NA counteracted the degenerative action of 6-OH-DA in both untreated and H44/68 pretreated rats. Intraocular NA did not interfere with the neurotoxicity of 6-A-DA. Additionally, octopamine did not affect the rate of autooxidation nor the neurotoxic potency of 6-OH-DA or 6-A-DA. Control experiments with 3-H-6-OH-DA showed that the intraneuronal NA levels did not significantly affect the intraneuronal accumulation of 6-OH-DA. The parallelism between the in vitro results on autooxidation and in vivo data on neurotoxicity makes it appear that the neurotoxic potency of 6-OH-DA and 6-A-DA is closely associated with their rates of autooxidation. The control of the degenerative action of 6-OH-DA by intraneuronal NA may be mediated via reaction of NA with radicals formed from oxygen during autooxidation of 6-OH-DA.

Animals↗
PubMed1975

5,7-Dihydroxytryptamine induced changes in the postnatal development of central 5-hydroxytryptamine neurons.

Systemic administration of the neurotoxic compound 5,7-dihydroxytryptamine (5,7-HT) to newborn rats led acutely (within 1--2 h) to a marked reduction of the in vitro uptake of [3H]5-hydroxytryptamine (5-HT) in homogenates from the cerebral cortex (75% decrease) and the pons-medulla (60% decrease). When 5,7-HT was administered postnatally we found that between days 5 an7 resistance developed in the cerebral cortex towards the 5,7-HT induced reduction in 3H-5-HT uptake. This was most likely the result of the postnatal development of the blood-brain barrier. These results show that 5,7-HT can pass the blood-brain barrier in the neonate stage and enter the brain to exert its well-known neurotoxic action on 5-HT neurons. The [3H]5-HT uptake in the cerebral cortex was reduced quantitatively to the same extent up to the 28th postnatal day, after which time a moderate recovery took place. Endogenous 5-HT was reduced by 40% in the cerebral cortex when measured in adult animals. In the pons-medulla there was a rapid recovery of the [3H]5-HT uptake during the first week after the 5,7-HT treatment and on the 14th postnatal day the increase was as much as 75% compared with the control. Endogenous 5-HT and [3H]5-HT uptake was increased by 40--50% when the analysis was performed 2 months after the 5,7-HT treatment. Studies of [3H]noradrenaline (NA) uptake after 5,7-HT administration at birth showed that this treatment similarly affected the NA neurons, though to a lesser extent. The effects on the NA neurons could be abolished by pretreatment with the "membrane pump" blocker desipramine, leaving the action of 5,7-HT on 5-HT neurons almost unaffected. Analysis of the [3H]5-HT uptake kinetics in the pons-medulla showed that the 5,7-HT treatment did not affect the Km while the Vmax was increased. It is concluded that neonatal 5,7-HT treatment produces a marked 5-HT denervation of the cerebral cortex, while there is a stimulated postnatal outgrowth of 5-HT nerve terminals in the pons-medulla, after an initial partial damage of the neurons.

Aging↗
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↗