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O Lindvall

Publications and source records attributed to O Lindvall.

At least 181 records · Page 10Linked to original sources
PubMed1984

Origin, course and termination of the mesohabenular dopamine pathway in the rat.

This study describes the organization of the mesohabenular dopamine (DA) system in the rat as revealed by fluorescence histochemistry in combination with lesions, DA uptake experiments and injections of a retrograde tracer. The DA axons were found to be aggregated in a dense terminal field located in the caudal two thirds of the medial part of the lateral habenular nucleus. Microknife lesions of the stria medullaris left this DA innervation unaffected while cuts through the fasciculus retroflexus resulted in the virtual disappearance of the DA innervation. Injections of the fluorescent retrograde tracer True Blue (TB) into the lateral habenula produced labeling of both DA and non-DA-containing cells in the ventral mesencephalon, mainly in the interfascicular nucleus ipsilateral to the injection. This study thus documents the existence of a mesohabenular DA pathway whose cell bodies are located in the ventral mesencephalon and whose axons ascend with the fasciculus retroflexus to terminate in the caudomedial part of the lateral habenular nucleus. This information, taken together with insights gained from other studies, suggests a role for the mesohabenular DA system in modulating telencephalic feedback onto the mesencephalic DA-neurons and also in regulating the output from the dorsal raphe nucleus.

Animals↗
PubMed1984

Selective histochemical demonstration of dopamine terminal systems in rat di- and telencephalon: new evidence for dopaminergic innervation of hypothalamic neurosecretory nuclei.

The distribution of dopamine (DA)-containing fibers in the virtual absence of noradrenaline (NA)-containing ones has been mapped by aldehyde fluorescence histochemistry in rats subjected to a combined neurotoxin treatment (intracerebral 6-hydroxydopamine injections plus systemic injections of the selective NA neurotoxin DSP-4). This pretreatment left di- and telencephalic DA levels largely unaffected, but reduced the NA levels by at least 86-96%. The resulting DA:NA ratios suggested that the catecholamine-containing structures, demonstrable by fluorescence histochemistry in the di- and telencephalic regions, were predominantly the DA-containing ones. While the distribution of DA terminal systems in the neo- and allocortical regions conformed well to previous results, the combined neurotoxin treatment revealed new features of the distribution of DA fibers in the diencephalon. In addition to the previously described innervations of the tubero-hypophyseal system, the incerto-hypothalamic system, and the mesohabenular pathway, previously unknown innervations were revealed in the supraoptic, paraventricular and dorsomedial nuclei of the hypothalamus, and in the paraventricular nucleus of the thalamus. Apart from some scattered fibers in the periventricular and lateral hypothalamic areas and medical zona incerta, other diencephalic nuclei seemed to be devoid of any significant DA terminal networks. The dopaminergic nature of these innervations is supported by DA uptake experiments (evaluated by fluorescence histochemistry) as well as by independent biochemical and immunohistochemical evidence. It is suggested that the DA innervations of the hypothalamic neurosecretory nuclei originate in cell bodies of the diencephalic A11-A14 cell groups and that such intradiencephalic DA projections participate in the regulation of oxytocin and vasopressin release from the pituitary.

Amygdala↗
PubMed1984

Cerebellar atrophy following phenytoin intoxication.

Cerebellar degeneration has been demonstrated in several patients receiving phenytoin therapy. In most cases it has been unclear, however, whether the degeneration was caused by the drug per se or by other mechanisms known to lead to cerebellar damage. We describe a patient who developed a marked cerebellar atrophy, demonstrated on computed tomographic scan, following an episode of acute, severe phenytoin intoxication. The patient received phenytoin prophylactically for 2 1/2 months after an uncomplicated subarachnoid hemorrhage and was in good health when the treatment was started. He has never had seizures, and no other possible cause of chronic cerebellar changes is known. The initially severe clinical signs of cerebellar dysfunction have subsided slowly. We conclude that phenytoin can directly cause cerebellar degeneration.

Adult↗
PubMed1984

Delayed postischemic hypoperfusion: evidence against involvement of the noradrenergic locus ceruleus system.

This study explores the possibility that the delayed hypoperfusion observed after an ischemic insult might be due to vasoconstriction induced by the release of noradrenaline from nerves originating in the locus ceruleus. Bilateral 6-hydroxydopamine lesions of the ascending bundles from the locus ceruleus were carried out in the caudal mesencephalon of rats. Local CBF was measured with an autoradiographic technique 60 min following the start of recirculation after incomplete forebrain ischemia. No significant differences in CBF between nonoperated, sham-operated, and noradrenaline-depleted animals were observed in any structure of the forebrain. It is concluded that the noradrenergic locus ceruleus system does not contribute to the development of delayed postischemic hypoperfusion.

Animals↗
PubMed1983

Influence of lesions of the noradrenergic locus coeruleus system on the cerebral metabolic response to bicuculline-induced seizures.

The objective of the present study was to explore if lesions of the ascending noradrenergic pathways, originating in the locus coeruleus, modulate the cerebral metabolic response to bicuculline-induced seizures in rats. Bilateral noradrenergic lesions were performed by 6-hydroxydopamine injections in the caudal mesencephalon, 12-22 days before seizures were induced in animals ventilated on N2O:O2 (75:25). After 5 min of seizures the brain was frozen in situ and cerebral cortex and hippocampus were sampled for analysis. Labile phosphates, glycolytic metabolites, cyclic nucleotides, and free fatty acids were measured. In another series, lesioned animals were used for measurements of cerebral oxygen consumption. The noradrenergic lesions neither modified the electroencephalographically recorded seizure discharge, nor did they alter cerebral oxygen consumption or cerebral energy state. However, when compared to sham-operated animals, those with noradrenergic lesions had significantly higher (115% and 68%) glycogen concentrations and lower (50% and 52%) cyclic AMP concentrations in cerebral cortex and hippocampus, respectively, demonstrating the marked influence of noradrenergic activity on adenylate cyclase activity and glycogenolysis. The lesions failed to modulate the rise in free fatty acids in the cerebral cortex, or the cyclic GMP concentrations in the cerebral cortex and hippocampus. Thus, increased noradrenergic activity during status epilepticus does not seem responsible for lipolysis or for activation of guanylate cyclase.

Animals↗
PubMed1983

Apomorphine-induced changes in local cerebral blood flow in normal rats and after lesions of the dopaminergic nigrostriatal bundle.

Systemic administration of the dopamine (DA) receptor agonist apomorphine leads to a general increase in cerebral blood flow (CBF) as determined by the autoradiographic iodoantipyrine technique. The magnitude of the increase varies between different regions but shows no obvious relation to the density of either DA terminals or receptors. The circulatory response is much more prominent in the lateral than in the medial caudate-putamen. Apomorphine seems to increase CBF both via a change in metabolic rate and via stimulation of dilatory vascular receptors. In animals with unilateral 6-hydroxydopamine lesions of the ascending DA pathways apomorphine induces an augmented CBF response in some denervated structures, notably caudate-putamen and globus pallidus. It is concluded that this is partly due to stimulation of denervated supersensitive vascular receptors, suggesting a direct dopaminergic control of the blood vessels in these areas.

Animals↗
PubMed1983

Dopamine-containing neurons in the spinal cord: anatomy and some functional aspects.

The anatomy of the recently discovered diencephalospinal dopaminergic system is summarized and its possible role in physiological and pathological processes suggested. The cell bodies of origin of this system are localized periventricularly in the dorsal hypothalamus and caudal thalamus, and the terminal innervations are found in the dorsal horn at all spinal levels and around the preganglionic sympathetic neurons in the thoracolumbar spinal cord. Available data favor the participation of the spinal dopaminergic system in pain modulation and autonomic and motor responses. Dysfunction of spinal dopaminergic neurons could be involved in the pathophysiology of certain conditions, such as Parkinson's disease. It appears possible that the beneficial effects of dopamine agonists in this condition as well as some of the side effects of neuroleptics are mediated through their actions on spinal dopaminergic mechanisms.

Animals↗
PubMed1982

Prefrontal cortex: dense dopaminergic input in the newborn rat.

Using a recently introduced modification of the aluminum-formaldehyde histofluorescence method, in combination with exogeneous administration of alpha-methylnoradrenaline and biochemical analyses, a remarkably advanced development of the dopaminergic and noradrenergic afferent to the frontal lobe has been demonstrated in neonatal rat. At birth, the density and general distributional pattern of the catecholamine innervation was similar to that found in the fully developed prefrontal cortex. The previously not recognized, early and extensive maturation of the mesocortical dopamine projection suggests a functional role of dopamine already in the early postnatal period.

Aging↗
PubMed1982

Functional activity of substantia nigra grafts reinnervating the striatum: neurotransmitter metabolism and [14C]2-deoxy-D-glucose autoradiography.

Dopaminergic innervation of the caudate nucleus in adult rats can be partially restored by the grafting of embryonic substantia nigra into the overlying parietal cortex with concomitant compensation of certain behavioral abnormalities. In this study the function of such grafts was investigated neurochemically by quantification of transmitter metabolism and glucose utilization in the reinnervated target. Rats with unilateral 6-hydroxydopamine lesions of the nigrostriatal bundle received a single graft to the dorsal caudate-putamen and were screened for rotational behavior following 5 mg/kg methamphetamine. The grafts restored dopamine concentrations in the caudate-putamen from initially less than 0.5% to an average of 13.6% of normal in rats with behavioral compensation. The ratio of 3,4-dihydroxyphenylacetic acid to dopamine, which is a measure of the rate of transmitter turnover, were equivalent in transplanted and normal control rats. Moreover, measurements of DOPA accumulation for a 30-min period after DOPA decarboxylase inhibition indicated similar fractional dopamine turnover rates in normal and transplant-reinnervated tissues. Correlations between rotational behavior and dopamine concentrations showed that reinnervation to only 3% of normal was sufficient to counterbalance the motor asymmetry. Measurements of glucose utilization by [14C]deoxyglucose autoradiography indicated equivalent metabolic rates for the grafted tissue and the intact substantia nigra. 6-Hydroxydopamine denervation of the caudate-putamen had no significant effect on neuronal metabolism in that region, nor did subsequent reinnervation from a graft. Grafts, however, were associated with a 16% reduction of glucose uptake in the ipsilateral globus pallidus, indicating a significant transsynaptic influence of the nigral transplants on neuronal metabolism in the host brain. Overall the results indicate that behaviorally functional neuronal grafts spontaneously metabolize dopamine and utilize glucose at rates characteristic of the intact nigrostriatal system. This provides further evidence that ectopic intracortical nigral transplants can reinstate dopaminergic neurotransmission in regions of the host brain initially denervated by the 6-hydroxydopamine lesion.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1981

Cerebral circulatory response to hypercapnia: effects of lesions of central dopaminergic and serotoninergic neuron systems.

The present study explores the possibility that the central dopaminergic and serotoninergic neuron systems influence CBF under normocapnic and hypercapnic conditions. In the first part of the study the effect of unilateral 6-hydroxydopamine lesion of the nigrostriatal dopamine pathway on local cerebral blood flow (1-CBF) was measured autoradiographically with [14C]iodoantipyrine as the diffusible tracer. The lesion caused no major effect on CBF under normocapnic or hypercapnic conditions. However, the circulatory response to hypercapnia was slightly enhanced (about 10%) in the denervated caudate-putamen. It is suggested that under hypercapnic conditions the pronounced increase in blood flow in the caudate-putamen is normally modulated by a slight vasoconstriction caused by dopamine release from the nigrostriatal system. In the second part of the study the effect of intraventricular 5,7-dihydroxytryptamine on cerebral metabolic rate for oxygen (CMRO2) and CBF was evaluated using a 133xenon modification of the Kety-Schmidt inert gas technique. The lesion, which removed about 90% of cortical 5-hydroxytryptamine, had no effect on the circulatory response to hypercapnia, not did it alter CMRO2. Under normocapnic conditions, though, the lesion seemed to induced a minor increase in CMRO2, which indicates that the serotoninergic system exerts a depressant resting tone on metabolic rate in the brain.

Animals↗
PubMed1981

Effects of methamphetamine on blood flow in the caudate-putamen after lesions of the nigrostriatal dopaminergic bundle in the rat.

Methamphetamine was given to rats with unilateral 6-hydroxydopamine lesions of the nigrostriatal dopaminergic bundle. In these animals local cerebral blood flow, measured autoradiographically with [14C]iodoantipyrine as the diffusible tracer, was more than twice as high in the denervated caudate-putamen as compared to control. Measurements of local glucose consumption with the [14C]deoxyglucose technique showed no corresponding change in local metabolic rate. In fact, glucose consumption was lower in the caudate-putamen on the lesion side. The results show that the amphetamine-induced increase in cerebral blood flow does not require an inact nigrostriatal dopaminergic system. Furthermore, dopamine released by amphetamine seems to constrict the vessels and reduce the blood flow in the caudate-putamen.

Animals↗
PubMed1981

Cerebral blood flow and oxygen consumption in the rat brain after lesions of the noradrenergic locus coeruleus system.

The effect of lesions of the locus coeruleus neuron system on cerebral metabolic rate for oxygen (CMRO2) and blood flow (CBF) was evaluated in paralyzed and mechanically ventilated rats, using a 133xenon modification of the Kety-Schmidt inert gas technique. Bilateral electrothermic lesions of its ascending bundle caused no significant change in CBF or CMRO2. The 6-hydroxydopamine lesions did not influence the CBF and CMRO2 responses to hypercapnia and hypoxia. It is concluded that the locus coeruleus does not exert any resting tone on CBF and CMRO2 and that no influence on the CBF and CMRO2 responses to hypercapnia and hypoxia is mediated via its ascending projections.

Animals↗
PubMed1981

Recent developments in aldehyde-induced monoamine fluorescence: the aluminum-formaldehyde (ALFA) method applied to immature and adult central nervous tissue.

In this review, the new aluminum-formaldehyde (ALFA) histofluorescence method for the highly sensitive visualization of monoamine-containing neurones in adult and immature central nervous tissue is summarized. Animals are first perfused with a buffer containing high concentrations of aluminum ions and the brains are then freeze-dried, reacted with formaldehyde vapour and further processed according to the Falck-Hillarp fluorescence method. The ALFA technique applied to adult brains visualizes all known catecholamine neurone systems with a sensitivity comparable to, and for certain noradrenergic systems higher than, that of the previously published glyoxylic acid-Vibratome method. The catecholamine systems in immature brains are demonstrated with a sensitivity clearly superior to that of any other available method. If the ALFA method is combined with systemic injections of alpha-methylnoradrenaline into young animals (less than one week old), there is a dramatic increase in the intensity and number of catecholaminergic fibres. Many catecholaminergic systems which have too low concentrations of transmitter to be visualized in the untreated animal even with the ALFA method, can be demonstrated after administration of alpha-methylnoradrenaline. The use of freeze-dried, paraffin-embedded tissue in the ALFA method makes possible convenient storage and parallel processing of many specimens. This mode of processing also allows en bloc reaction, which is the only way by which consistent and reproducible fluorescence yields can be obtained throughout large series of sections and parallel-processed specimens. In animals pretreated with L-tryptophan and monoamine oxidase-inhibitor, the technique is also useful for studies on central indolamine-containing systems.

Age Factors↗
PubMed1980

New aspects on factors determining the sensitivity of the formaldehyde and glyoxylic acid fluorescence histochemical methods for monoamines.

The fluorophore and fluorescence yield from tryptamine and 3-methoxytyramine in histochemical protein models have been compared in the standard formaldehyde reaction, the acid-catalyzed formaldehyde reaction, the formaldehyde-ozone reaction, and the aluminum-formaldehyde reaction. In the standard formaldehyde reaction both the fluorophore and fluorescence yields are low. However, the other reactions give a dramatic increase in fluorescence intensity (18-20 times) from tryptamine and 3-methoxytyramine whereas only minor changes (up to 100% increase) in fluorophore yield are observed. It is concluded that the relative fluorescence intensity of each fluorophore molecule formed in the three modifications of the formaldehyde reaction is much higher than that of the molecules formed in the standard formaldehyde reaction. It has previously been demonstrated that the fluorophores formed from dopamine in the gaseous formaldehyde and glyoxylic acid reactions have a much higher (10 times) relative fluorescence intensity than the synthetic fluorophores. the prresent experiments show that if the histochemicl models are dissolved in buffer after the reaction and new models are made from this solution, the fluorescence intensity of the fluorophores formed in the reaction is drastically reduced and becomes comparable to that of the synthetic ones. The results of this and our previous studies indicate that hitherto unknown fluorescence enhancing mechanisms play a major role for the fluorescence yield, i.e. the sensitivity, in the various formaldehyde and glyoxylic acid methods. One possible explanation to the high relative fluorescence intensity of the fluorophores formed in the histochemical reactions could be an energy transfer between, e.g. the non-fluorescent intermediary reaction products (the tetrahydro derivatives) and the fluorophores (the dihydroisoquinolines and dihydro-beta-carbolines). Such an energy transfer is probably attenuated in the dissolved models, where th distances betweenm and orientations of the various molecules have been changed.

Dopamine↗
PubMed1980

The aluminum-formaldehyde (ALFA) histofluorescence method for improved visualization of catecholamines and indoleamines. I. A detailed account of the methodology for central nervous tissue using paraffin, cryostat or Vibratome sections.

This present paper presents a new aluminum-formaldehyde (ALFA) histofluorescence method for highly sensitive visualization of central monoamine-containing neurons, based on perfusion with or immersion in buffers containing high concentrations of aluminum ions. Our previous studies have shown that perfusion or immersion of tissues with solutions containing high concentrations of magnesium results in an improvement in the visualization of intraneuronal catecholamines in the reaction with formaldehyde and glyoxylic acid. This study demonstrates that aluminum is considerably more efficient as a fluorescence-promoting agent, thus causing a further increase in the sensitivity of the formaldehyde method. Detailed protocols are given for the ALFA-method applied to paraffin sections of freeze-dried tissue, and to cryostat and Vibratome sections. The present ALFA technique applied to paraffin sections of freeze-dried tissue visualizes all known catecholamine neuron systems with a sensitivity comparable to, and for certain noradrenergic systems higher than, that of the previously published glyoxylic acid-Vibratome method. Furthermore, the use of freeze-dried, paraffin embedded tissue makes possible convenient storage and parallel processing of many specimens. This mode of processing also allows en bloc reaction, which is the only way by which consistent and reproducible fluorescence yields can be obtained throughout large series of sections and parallelly processed specimens. In animals pretreated with L-tryptophan and MAO-inhibitor the technique is also useful for studies on central indoleamine-containing systems in freeze-dried tissue. The ALFA procedure applied to cryostat and Vibratome sections gives a more sensitive and reproducible visualization of central catecholamine neurons than previous methods.

Aluminum↗
PubMed1980

The aluminum-formaldehyde (ALFA) histofluorescence method for improved visualization of catecholamines and indoleamines. 2. Model experiments.

The fluorescence-promoting effects of sodium, magnesium and aluminum ions in the histochemical formaldehyde (FA) reaction with catecholamines and indoleamines have been studied in protein models. The positive effects of aluminum and magnesium salts on the monoamine fluorescence yields, seen in tissue, could partly be reproduced in a simple protein matrix. The fluorescence-promoting potency was greatest for aluminum, moderate for magnesium and small for sodium. The aluminum effect was markedly concentration-dependent, with an optimum at a concentration of 5-10 mM in the model solution. Optimum pH was around 3.8. Experiments with synthetic fluorophores indicate that the principal action of the metal ions is on the fluorescence properties of the monoamine fluorophores rather than on the yield of fluorophores in the reaction of the monoamines with FA. The presence of aluminum ions in the models thus causes both increases in the fluorescence efficiency of the fluorophores as well as changes in their spectral properties. The direct effects on the monoamine fluorophores cannot, however, account for all effects of the metal salts seen in tissue. It is suggested that aluminum and magnesium ions, in addition, can act as acid catalysts in the FA-monoamine reactions, and that the metal salts have a direct effect on the tissue environment, leading to a 'locking-in' of the intracellular monoamines.

Aluminum↗