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Biomedical subjects

K Fuxe

Publications and source records attributed to K Fuxe.

At least 469 records · Page 26Linked to original sources
PubMed1986

Preferential vulnerability of A8 dopamine neurons in the primate to the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.

Immunohistochemical examination of the midbrain of vervet monkeys treated with MPTP revealed a marked loss of dopaminergic neurons in the lateral, but not medial, region of the A8 dopamine (DA) cell group. In the same animals, the number of DA neurons in the substantia nigra was only slightly decreased. Biochemical assessment revealed a marked (greater than 85%) depletion of DA in the striatum. However, in the DA cell body regions significant decreases in DA and homovanillic acid were observed only in the lateral A8 region, and not in the medial A8 region or substantia nigra. These data suggest that those A8 DA neurons which project to the striatum are preferentially vulnerable to MPTP.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1986

Analysis of [3H]spiperone binding sites in the rat striatum and frontoparietal cortex by means of quantitative receptor autoradiography after inactivation of dopamine receptors by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline in vivo: selective protection by sulpiride in the striatum.

By means of quantitative receptor autoradiography in combination with inactivation of dopamine (DA) receptors by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ), it was demonstrated in the male rat that [3H]spiperone predominantly labels D2 receptors in the striatum, nucleus accumbens and tuberculum olfactorium, and predominantly non-DA receptors in the frontoparietal cortex, probably mainly serotonin type 2 (5-HT2) receptors in layer IV. Furthermore, the [3H]spiperone-labelled D2 receptors found all over the dorsal and ventral striatum appear to be similarly inactivated by EEDQ and protected by the D2 antagonist (+/-) sulpiride but not the D1 antagonist SCH 23390, indicating a homogeneity of the striatal D2 receptors.

Animals↗
PubMed1986

Increases in dopamine utilization in certain limbic dopamine terminal populations after a short period of intermittent exposure of male rats to cigarette smoke.

By means of a Walton smoke machine male rats were exposed to cigarette smoke from 1 to 4 cigarettes. Dopamine (DA) levels and utilization in the telencephalon were measured by quantitative histofluorimetry in discrete DA nerve terminal systems of the neostriatum, nucleus accumbens and tuberculum olfactorium. Exposure to unfiltered but not to filtered (Cambridge glass fibre filter) cigarette smoke resulted in a dose-dependent increase in DA utilization in the diffuse types of DA nerve terminal systems in the anterior nucleus accumbens and the lateral posterior tuberculum olfactorium. After exposure to the smoke from 4 cigarettes also an increase in DA utilization was observed in the dotted type (also cholecystokinin [CCK] positive) of DA nerve terminals of the nucleus accumbens (posterior part). The DA utilization in various parts of the neostriatum and in the dotted type of DA nerve terminals in the medial posterior tuberculum olfactorium were unaffected by acute intermittent exposure to cigarette smoke. The DA levels in the various DA nerve terminal systems in neostriatum, nucleus accumbens and tuberculum olfactorium were unaffected with the exception of the dotted and CCK positive type of DA nerve terminals of the nucleus accumbens, where a small reduction of the DA stores was shown following acute intermittent exposure to smoke from 4 cigarettes. The effects induced by exposure to the cigarette smoke in the limbic DA terminals were counteracted by mecamylamine pretreatment. It is suggested that the nicotine component of the cigarette smoke via activation of nicotinic cholinergic receptors can enhance DA release in discrete DA nerve terminal systems of the nucleus accumbens and tuberculum olfactorium. These actions may at least in part mediate the euphoria induced by inhalation of cigarette smoke.

Animals↗
PubMed1986

Neuropeptide Y enhances the inhibitory effects of clonidine on 3H-noradrenaline release in synaptosomes isolated from the medulla oblongata of the male rat.

In studies on superfused synaptosomes from the rat medulla oblongata, the inhibitory effects of the alpha 2-adrenergic agonist clonidine (0.1 microM) on potassium (15 mM K+) induced 3H-noradrenaline (NA) release was potentiated by 20%, when neuropeptide Y was added to the system. The effect of NPY was detectable at low concentrations (1 nM) and was not dose-dependent. Neuropeptide Y alone produced no significant effects on 3H-NA release. The results may indicate the existence of a presynaptic NPY receptor on the noradrenaline and/or adrenaline nerve terminals, which may enhance the presynaptic alpha 2-adrenoreceptor function to inhibit 3H-NA release.

Animals↗
PubMed1986

Glucocorticoid mechanism of action: monoclonal antibodies as experimental tools.

In order to provide a further insight into glucocorticoid receptor (GR)-mediated action of glucocorticoid hormones, we produced ten monoclonal antibodies against rat GR. In studies combining physicochemical separation methods with antibody methodology, we established that the molybdate-stabilised GR contains one steroid-binding monomer. Using a monoclonal anti-GR antibody-based immunoaffinity chromatographic procedure, we purified two non-ligand-binding proteins, with molecular weights of 80,000 and 90,000, present in the molybdate-stabilised GR complex. These proteins are not recognised by monoclonal antibodies directed against GR. The possible relation of these two proteins to heat shock proteins remains to be established. Immunohistochemical studies of GR in the central nervous system of the rat provided new information on the distribution of GR, particularly in the hypothalamus. Studies of intracellular receptor localisation in rat brain after endocrine manipulations gave results in support of the classical concept of translocation of GR from cytoplasm to cell nucleus. Studies with a cell culture system also supported the existence of GR in the cytoplasm as well as in the cell nucleus.

Animals↗
PubMed1986

Glucocorticoid receptor immunoreactivity in monoaminergic neurons of rat brain.

A monoclonal antibody against the rat liver glucocorticoid receptor was used in combination with rabbit antibodies against tyrosine hydroxylase, phenylethanolamine N-methyltransferase, and 5-hydroxytryptamine to demonstrate strong glucocorticoid receptor immunoreactivity in large numbers of central monoaminergic nerve cell bodies of the male rat. The receptor immunoreactivity was predominantly located in the nucleus, whereas the tyrosine hydroxylase, phenylethanolamine N-methyltransferase, and 5-hydroxytryptamine were detected mainly in the cytoplasm. The vast majority of the noradrenergic nerve cell bodies of groups A1-A7 and of the 5-hydroxytryptaminergic cell bodies of groups B1-B9 were found to contain strong glucocorticoid receptor immunoreactivity. The majority of the phenylethanolamine N-methyltransferase-immunoreactive nerve cells of the adrenergic cell groups C1-C3 and of the dorsal subnuclei of the nucleus tractus solitarius in the medulla oblongata were also strongly immunoreactive for glucocorticoid receptor. In the midbrain dopaminergic groups A8-A10, moderately (A8, A9) to strongly (A10) glucocorticoid receptor-immunoreactive cells were found, ranging from 40 to 75% of the total population. In the hypothalamic dopaminergic cell groups, all the cells of groups A12 and A14, as well as the majority of the dopaminergic cells of the zona incerta (A13), were found to contain moderate to strong glucocorticoid receptor immunoreactivity, but none of the large dopaminergic cells of the posterior hypothalamus (A11) showed such immunoreactivity.

Amines↗
PubMed1986

Intravenous uridine treatment antagonizes hypoglycaemia-induced reduction in brain somatostatin-like immunoreactivity.

By means of radioimmunoassay procedures, cholecystokinin-(CCK) and somatostatin-(SRIF) like immunoreactivity have been studied in the dorsal hippocampal formation and in the frontoparietal cortex of the male rat in insulin-induced hypoglycaemia, leading to an isoelectric EEG pattern. It has been demonstrated that severe hypoglycaemia of 40-min-duration produces a disappearance of SRIF but not of CCK-like immunoreactivity in both cortical regions. It was found that an i.v. injection of uridine but not of saline could significantly counteract the disappearance of SRIF-like immunoreactivity induced by severe hypoglycaemia in both cortical areas. Uridine did not by itself change plasma glucose levels. It is suggested that uridine may prevent release and/or increase synthesis of cortical SRIF peptides in severe hypoglycaemia, possibly due to an action on the metabolism (e.g. by enhancing the resynthesis of phosphatidyl inositol) within the tissue of the cerebral cortex and/or on putative pyrimidine binding sites in the brain controlling SRIF synthesis and/or release. It is possible that uridine in this way may improve recovery of neuronal function within SRIF-immunoreactive neurons of the cerebral cortex after severe hypoglycaemia (which also may be true in other states of reduced metabolic support). These findings suggest a possibility to use uridine in the treatment of Alzheimer's disease and Status epilepticus.

Animals↗
PubMed1986

Quantitative autoradiography of central neurotransmitter receptors: methodological and statistical aspects with special reference to computer-assisted image analysis.

In the last few years, quantitative receptor autoradiography has been extensively employed to study the distribution and the functional role of area-specific transmitter receptors in the central nervous system. In the present paper we have developed quantitative methodologies for the analysis of autoradiograms using computerized image analysers coupled with standard TV camera input for the microdensitometrical evaluations. These procedures include the assessment of the film response to radioactivity using appropriate standards calibrated according to brain tissue quenching and non-linear conversion of density measurements in radioactivity values adopting the best mathematical model fitting to give as little variability as possible in the transformations. The reliability of the proposed approach has also been evaluated by means of a computer-assisted Monte Carlo simulation and parallel biochemical determinations.

Animals↗
PubMed1986

Receptor autoradiographical evidence for high densities of 125I-neuropeptide Y binding sites in the nucleus tractus solitarius of the normal male rat.

By means of quantitative receptor autoradiography using 125I-neuropeptide Y (125I-NPY) as a radioligand, the distribution of 125I-NPY binding sites has been evaluated in coronal sections at various rostrocaudal levels of the medulla oblongata of the male rat. High densities of neuropeptide Y (NPY) binding sites were demonstrated in the nucleus tractus solitarius (nTS), in the nucleus paratrigeminalis, in the area postrema, in the medial nuclei of the inferior olive and in the substantia gelatinosa of the caudal part of the spinal trigeminal nucleus. Low densities were present in the dorsal motor nucleus of the vagus (dmnX) and in the hypoglossal nucleus. Other regions of the medulla oblongata showed only a very low density or no specific binding of 125I-NPY. These results indicate that the central cardiovascular actions of NPY at least in part may be mediated via an action in the nTS, in this way controlling the baroreceptor reflex activity. Neuropeptide Y mechanisms may also play a role in the regulation of other visceral afferents such as those involved in gastrointestinal control (dmnX) and of cerebellar function (inferior olive). Finally, the results indicate that a high density of NPY immunoreactive terminals in some regions of the medulla oblongata is associated with a low density of high affinity 125I-neuropeptide Y binding sites and vice versa.

Animals↗
PubMed1986

A correlation analysis of the regional distribution of central enkephalin and beta-endorphin immunoreactive terminals and of opiate receptors in adult and old male rats. Evidence for the existence of two main types of communication in the central nervous system: the volume transmission and the wiring transmission.

By means of semiquantitative immunocytochemistry and quantitative receptor autoradiography a correlation analysis has been performed on the pre- and post-synaptic features of enkephalin and beta-endorphin immunoreactive neuron systems of the 3- and 24-month-old male rat. A parallel disappearance of enkephalin- and beta-endorphin-like immunoreactivity and of the density of mu and delta opiate receptors is shown during ageing. Furthermore, the lack of an overall correlation between the amount of pre- and post-synaptic components of the enkephalin and beta-endorphin synapses give evidence for the existence of a volume type of transmission in such systems in the telencephalic, diencephalic and mesencephalic areas analysed.

Age Factors↗
PubMed1986

Evidence that intracisternal injections of cholecystokinin-8 counteracts the cardiovascular effects of intracisternally injected adrenaline and neuropeptide Y in the alpha-chloralose anaesthetized rat.

Recently evidence has been obtained for the coexistence of adrenaline (A), neuropeptide Y (NPY) and cholecystokinin (CCK) in the same neurons located in the dorsal subnuclei of the nucleus tractus solitarius (nTS). Furthermore, receptor autoradiographical studies show a partial overlap between alpha 2, NPY and CCK receptors in this area. In the present study intracisternal (i.c.) co-administration of A/CCK-8 SO4 and NPY/CCK-8 SO4 was performed. Sulphated CCK-8 counteracted the hypotensive responses of NPY and A in the alpha-chloralose anaesthetized male rat. One possible explanation may be that the A/NPY/CCK neurons, which may be directly innervated by the baroreceptor afferents, release CCK peptides as endogenous antagonists to modulate the adrenergic/NPY-ergic transmission lines via a receptor-receptor interaction. An additional explanation is the possibility that the interaction between CCK, NPY and adrenaline takes place at the network level.

Anesthesia↗
PubMed1985

Effects of neurotoxic and mechanical lesions of the mesostriatal dopamine pathway on striatal polyamine levels in the rat: modulation by chronic ganglioside GM1 treatment.

In male rats, partial hemitransections but not 6-hydroxydopamine (6-OHDA)-induced lesions of the mesostriatal dopamine (DA) pathway produce after 7 days a marked and a modest increase of striatal putrescine and spermidine levels, respectively, on the lesioned side. Following chronic ganglioside GM1 treatment of partially hemitransected rats, an increase of striatal polyamine levels was observed also on the intact side. It is suggested that retrograde cell body changes produced by hemitransection may induce striatal ornithine decarboxylase activity and in this way increase striatal putrescine levels, favoring regenerative mechanisms. The increase of striatal polyamine levels by GM1 treatment on the intact side of both 6-OHDA and mechanically lesioned rats compared with intact unoperated rats may also reflect an increased synthesis of striatal polyamines.

Animals↗
PubMed1985

Immunocytochemical studies on the localization of glucocorticoid receptor immunoreactive nerve cells in the lower brain stem and spinal cord of the male rat using a monoclonal antibody against rat liver glucocorticoid receptor.

By means of the indirect immunoperoxidase method glucocorticoid receptor (GR) immunoreactive nerve cells of the lower brain stem and the spinal cord have been mapped out in the rat, using a monoclonal antibody against rat liver GR. The GR immunoreactivity was predominantly located within the nuclei of these nerve cell bodies but also in glial cells of the gray and white matters. Strongly GR immunoreactive nerve cells were mainly found in the area of the noradrenaline, adrenaline and 5-hydroxytryptamine (5-HT) cell groups of the lower brain stem, and of the substantia gelatinosa of the nuc. tractus spinalis nervi trigemeni and spinal cord. The results suggest that glucocorticoids control transmitter and metabolic functions in discrete areas of the brain stem and spinal cord.

Animals↗
PubMed1985

Rat medulla oblongata. I. Cytoarchitectonic considerations.

The goal of this study was to define the detailed cytoarchitecture of the medulla oblongata of the rat in order to accurately localize immunocytochemically distinct populations of neurons in this region. The cytoarchitectonic features of this region of the rat brain stem were examined in 40 micron thick serial sections of celloidin embedded brains blocked in the Horsley-Clarke stereotaxic plane. These sections were stained with cresyl violet and examined at a number of different magnifications with a variety of different intensities of staining to demonstrate particular features of the cells in this region. High magnification photomicrographs of this material revealed characteristic features of the various populations of cells. The results illustrate that the cytoarchitecture of the medulla oblongata of the rat changes remarkably within very short distances in the rostrocaudal direction. These changes indicate the need to study the anatomy and immunocytochemistry of this region in detailed serial sections. The ventral reticular formation of the rat medulla is cytoarchitectonically complex. Nuclear groups such as the lateral reticular nucleus (LRt) contain a number of cytoarchitectonically distinct subnuclei, as does the dorsally located nucleus of the tractus solitarious (nTS) (Kalia and Sullivan, '82). These nuclei occupy a considerable length of the medulla and terminate abruptly at the pontomedullary boundary. A number of other cytoarchitectonic features of the medulla were examined and the detailed characteristics were defined.

Animals↗