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K Fuxe

Publications and source records attributed to K Fuxe.

At least 487 records · Page 27Linked to original sources
PubMed1985

Rat medulla oblongata. II. Dopaminergic, noradrenergic (A1 and A2) and adrenergic neurons, nerve fibers, and presumptive terminal processes.

The aim of this study was to determine the anatomical relationships between catecholaminergic neurons and cytoarchitectonically defined nuclei in the caudal medulla oblongata. Previous studies have demonstrated the existence of noradrenergic cell bodies (designated as the A1 and A2 cell groups) in the caudal medulla oblongata of the rat (Dahlström and Fuxe, '64), including the nTS. There is no information currently available with regard to details of the distribution of these noradrenergic neurons in the functionally distinct subnuclei of the medulla oblongata. In this study the location of catecholamine-synthesizing enzymes was examined in the serial sections of the caudal medulla oblongata of the rat: tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH), and phenylethanolamine N-methyl transferase (PNMT). The immunoperoxidase method of Sternberger ('79) was used to demonstrate the location of immunoreactive neurons, nerve fibers, and presumptive terminal processes. This was followed by Nissl staining of the same sections to localize accurately the immunoreactivity. Noradrenergic neurons (TH- and DBH-positive and PNMT-negative) were localized in a number of subnuclei of the nucleus of the tractus solitarius (nTS), the area postrema (ap), and in the dorsal motor nucleus of the vagus (dmnX). The distribution of these noradrenergic cells was different at different rostrocaudal levels. In addition, adrenergic neurons (TH-, DBH-, and PMNT-positive) were identified dorsal to the tractus solitarius (TS), in the dorsal strip region (ds), the periventricular region (PVR), the dorsal parasolitarius region (dPSR), and the dmnX (rostral to obex). In addition, dopaminergic neurons (TH-positive and DBH- and PNMT-negative) were found in the ap and dmnX. The A1 cell group in the ventrolateral medulla consisted almost exclusively of noradrenergic neurons (TH- and DBH-positive and PNMT-negative). These results indicate that in the rat the A2 cell group is a mixed population of catecholaminergic neurons that are localized in well-defined regions of the dorsal medulla oblongata. The distribution of these neurons is very specific both in terms of rostrocaudal levels and cytoarchitectonic subdivisions of regions of the medulla known to be involved in central autonomic control. This supports the hypothesis that monoaminergic neurons in the dorsal medulla play important roles in the central regulation of visceral function.

Adrenergic Fibers↗
PubMed1985

Rat medulla oblongata. III. Adrenergic (C1 and C2) neurons, nerve fibers and presumptive terminal processes.

The goal of this study was to define the cytoarchitectonic relationships between the catecholaminergic cell groups (the C1 and C2) in the rostral medulla oblongata of the rat. Immunocytochemistry was combined with Nissl staining to determine the nuclear boundaries in this region of the brain stem. In addition, the morphological characteristics of neurons in the C1 and C2 cell groups were determined and the relationship between these populations of neurons and their caudaul counterparts (A1 and A2 cell groups) was established (Kalia et al., '85a). The results indicate that the C1 and C2 cell groups are distributed over a wide region of the rostral medulla. The location of these adrenergic neurons is related to a number of nuclear groups in this region. This finding was remarkably consistent in all the animals studied in this series. In addition, adrenergic nerve fibers were found to be distributed over a large region of the medullary reticular formation. There was homogeneity in the morphology of the C1 and C2 cell groups. These rostrally located adrenergic neurons did not share morphological features in common with the recently described (Kalia et al., '85a) caudally located adrenergic neurons in the dorsal region of the nucleus of the tractus solitarius. These striking anatomical features of the adrenergic C1 and C2 cell groups support the proposal that adrenergic neurons in the rostral medulla oblongata play an important role in the integration of visceral functions (Fuxe et al., '80).

Adrenergic Fibers↗
PubMed1985

Rat medulla oblongata. IV. Topographical distribution of catecholaminergic neurons with quantitative three-dimensional computer reconstruction.

We examined serial 40 micron vibratome, immunoperoxidase-stained sections of the medulla with tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH), and phenylethanolamine N-methyltransferase (PNMT) antisera followed by Nissl staining to locate catecholaminergic neurons in cytoarchitectonic regions followed by a three-dimensional (3D) computer reconstruction of these cell groups to determine their spatial organization. Overlay drawings of low and high power photomicrographs showing cell bodies and nuclear boundaries were entered into a digital computer storage system. Every section in the series was plotted to yield an accurate representation of regional densities of cells and location of nuclei, as revealed by two-dimensional plots of individual sections as well as three-dimensional plots of groups of sections. Data files were scanned in a number of ways to obtain total cell counts of TH-, DBH-, and PNMT-immunoreactive cells within a designated area or cell counts of only one type of immunoreactive cell. This combination of data manipulation produced the following results: (1) A1 group is a homogeneous population of noradrenergic neurons at levels caudal to the obex, and at the obex it is mixed with adrenergic cells. The dimensions of the A1 cell group are 1.3 X 2.7 mm, extending from -2.5 to +0.2. Part of this cell group lies in the lateral reticular nucleus. (2) A2 group is not purely noradrenergic as previously suspected. It is a very mixed cell group containing mainly dopaminergic neurons in the area postrema (periventricular region) and the dorsal motor nucleus of the vagus, mainly noradrenergic neurons in the medial subnucleus of the nucleus of the tractus solitarius (nTS), mainly adrenergic neurons in the dorsal strip and dorsal subnucleus of the nucleus of the tractus solitarius, and a mixture of all three catecholaminergic neurons in the other subnuclei of the nTS. The dimensions of this group are 0.4 X 3 mm extending from -2.7 to +0.3. (3) C1 group is a homogeneous population of adrenaline cells extending from +1 to +2.5 with dimensions of 1.5 X 1.5 mm and consisting of scattered neurons some of which occupy the gigantocellular reticular nucleus. (4) C2 group is a homogeneous population of adrenaline neurons extending from +1 to +3 with dimensions of 2.5 X 3 mm. Accurate visual imaging and quantitation of the spatial organization of medullary catecholaminergic neurons within the classical anatomical framework of cytoarchitecture provides an enhanced comprehension of the organization of this region of the central nervous system.

Animals↗
PubMed1985

Morphometrical analysis of the distribution of corticotrophin releasing factor, glucocorticoid receptor and phenylethanolamine-N-methyltransferase immunoreactive structures in the paraventricular hypothalamic nucleus of the rat.

By means of the indirect immunoperoxidase technique the corticotrophin releasing factor (CRF) and glucocorticoid receptor (GR) immunoreactive nerve cell bodies and the phenylethanolamine-N-methyltransferase (PNMT) immunoreactive nerve terminals in the paraventricular hypothalamic nucleus of the rat have been mapped out in adjacent vibratome sections (30 micron thick). By means of morphometrical analysis using a semiautomatic image analyser, it was possible to obtain density maps of CRF, GR and PNMT immunoreactive structures within the paraventricular hypothalamic nucleus. The statistical analysis by the use of correlation coefficients gives evidence that the PNMT immunoreactive nerve terminals innervate the majority of the CRF immunoreactive nerve cell bodies and that GR are located in the majority of the CRF immunoreactive neurons.

Animals↗
PubMed1985

Central dopamine agonist activity on the 8-alpha-amino-ergoline CU 32-085.

The effects of the 8-alpha-amino-ergoline CU 32-085 on central dopamine neuronal systems was investigated. Two h after administration of CU 32-085 a slight increase of dopamine levels was observed in the nucleus caudatus-putamen. Radioligand binding studies in vitro have shown that CU 32-085 has a low affinity for striatal dopamine receptors labeled by [3H]n-propylapomorphine or [3H]spiroperidol. However, CU 32-085 effectively displaces in vivo [3H]n-propylapomorphine and [3H]spiroperidol from their respective binding sites in the mouse striatum. Functional studies have shown that CU 32-085 elicits contralateral rotation in rats with unilateral 6-OH-dopamine induced lesions of the meso-striatal dopamine neurons, and ipsilateral rotation in rats with unilateral intrastriatal ibotenic acid lesions. CU 32-085 relieves tremor in monkeys with ventromedial tegmental lesions and produces only slight abnormal involuntary movements. The biochemical and functional studies suggest that CU 32-085 and/or its metabolite exerts central dopamine agonist activity in vivo. Studies in monkeys with ventromedial tegmental lesions suggest that CU 32-085 might be an effective antiparkinsonian agent which produces less dyskinesias than the other tested dopamine agonists.

Animals↗
PubMed1985

The importance of brain serotonergic receptor mechanisms for the action of antidepressant drugs.

The present studies have shown that chronic antidepressant treatment with different types of antidepressant drugs results in adaptive changes in postsynaptic 5-HT receptor mechanisms which appear to result in 5-HT sub- or supersensitivity development depending upon the 5-HT nerve terminal system analyzed. The results underline the heterogeneity of the central 5-HT neuron systems in their responses to chronic antidepressant treatment. In addition, a number of antidepressant drugs have potent, direct actions on 5-HT2 receptors, which may be of clinical relevance.

Animals↗
PubMed1985

Effects of lesions and ganglioside GM1 treatment on striatal polyamine levels and nigral DA neurons. A role of putrescine in the neurotropic activity of gangliosides.

The effects of a partial hemitransection at the meso-diencephalic level, with or without chronic ganglioside GMI treatment, have been evaluated on striatal polyamine levels, 7, 14 and 21 days after lesion, as well as on the ability of the polyamine synthesis inhibitor alpha-difluoromethylornithine (alpha-DFMO) to modulate the protective effects of chronic ganglioside GMI treatment against retrograde degeneration of the nigral dopamine (DA) nerve cell bodies (14 day time interval). The striatal polyamine levels were measured by high pressure liquid chromatography after dansylation of the polyamines. The nigral DA nerve cells were studied by means of tyrosine hydroxylase (TH) immunocytochemistry using the indirect immunoperoxidase technique. Quantitation was performed by means of morphometrical evaluation of the TH immunoreactive area of the substantia nigra. Seven days after partial hemitransection there is a marked increase (above 350%) in striatal putrescine levels, which is not modulated by chronic GMI treatment. This marked increase could, to a large extent, be counteracted by simultaneous treatment with alpha-DFMO, which blocks mainly the synthesis of putrescine. Twenty-one days after lesion chronic GMI treatment could produce an increase in striatal putrescine levels on the intact side and also after this time-interval prevent the reduction of striatal spermine levels. It was also found that simultaneous treatment with alpha-DFMO prevents the development of the protective action of chronic ganglioside GMI treatment against retrograde degeneration of the nigral DA neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Determinations of catecholamine half-lives and turnover rates in discrete catecholamine nerve terminal systems of the hypothalamus, the preoptic region and the forebrain by quantitative histofluorimetry.

To determine whether amine pool sizes, half-lives and turnover rates could be measured in discrete hypothalamic, preoptic and forebrain catecholamine (CA) nerve terminal networks by quantitative histofluorimetry, the CA fluorescence disappearance was studied at different time intervals after tyrosine hydroxylase inhibition. For comparison, the depletion of DA and NA following tyrosine hydroxylase inhibition in discrete brain regions was determined by high pressure liquid chromatography (HPLC). Following tyrosine hydroxylase inhibition using alpha-methyl-DL-p-tyrosine methyl ester, an apparently monophasic decline of the CA stores was demonstrated in all brain regions analysed both histochemically and by HPLC. A multiphasic DA disappearance was measured by HPLC in the peri- and paraventricular hypothalamic area. The DA nerve terminal networks generally had shorter half-lives than the NA nerve terminal networks. The shortest half-life (99 min) of the regions demonstrating a monophasic decline of CA stores was found in the CA nerve terminal system in the medial palisade zone of the median eminence. By the use of CA standards in the histochemically prepared sections, it was possible to convert the measured CA fluorescence into absolute amounts of catecholamines expressed in nmol X g-1 of tissue wet weight. It was shown that the CA stores and the turnover rates measured by quantitative histofluorimetry were 20-30 times greater than those measured using HPLC. The difference has been related to amine dilution with amine-poor areas in the specimens analysed by HPLC. By studying the accumulation of catecholamines after monoamine oxidase inhibition, it could be demonstrated that no concentration-dependent quenching of CA fluorescence occurred.

Animals↗
PubMed1985

Effects of acute intermittent exposure to cigarette smoke on catecholamine levels and turnover in various types of hypothalamic DA and NA nerve terminal systems as well as on the secretion of adenohypophyseal hormones and corticosterone.

Male rats were exposed to cigarette smoke (Walton Horizontal Smoking Machine) from one to four cigarettes (Kentucky reference IR-1 type). Catecholamines in the diencephalon were measured by quantitative histofluorimetry in discrete dopamine (DA) and noradrenaline (NA) nerve terminal systems. Blood TSH, prolactin, LH, FSH, ACTH, vasopressin and corticosterone levels were determined by radioimmunoassay procedures. Exposure to unfiltered, but not to filtered (Cambridge glass fibre filters) cigarette smoke resulted in dose-dependent reductions of NA levels in the various hypothalamic NA nerve terminal systems. Evidence was obtained that exposure to unfiltered but not to filtered cigarette smoke resulted in dose-dependent increases of amine turnover (alpha MT-induced CA disappearance experiments) in the various DA and NA nerve terminal systems in the hypothalamus. The lowering of TSH, LH and prolactin secretion induced by unfiltered smoke were probably induced by nicotine and were independent of tyrosine hydroxylase inhibition. Furthermore, unfiltered cigarette smoke produced a dose-related increase in corticosterone secretion. The inhibitory effects of TSH, LH and prolactin secretion were probably in part related to the ability of unfiltered smoke via its nicotine component to activate the lateral and medial tubero-infundibular DA neurons. The increases in corticosterone secretion may at least in part be related to a smoke induced increase in the facilitatory influence of paraventricular NA nerve terminals on CRF activity.

Adrenocorticotropic Hormone↗
PubMed1985

Effects of ganglioside GM1 treatment on striatal glucose metabolism, blood flow, and protein phosphorylation of the rat.

Effects of ganglioside GM1 administration have been studied in unilaterally partially hemitransected rats on striatal energy metabolism, using the radioactive deoxyglucose (DG) technique, on striatal blood flow, using radiolabelled iodoantipyrine (IAP) as tracer, and on cyclic AMP (cAMP) and Ca2+ induced protein phosphorylation in striatal membranes (P2 fraction). Ganglioside GM1 treatment counteracted the imbalance in striatal energy metabolism, in striatal blood flow, as well as in protein phosphorylation found between the striata of the lesioned and unlesioned side, possibly due to excitatory effects on the lesioned side and inhibitory effects on the unlesioned side. In intact animals, GM1 treatment produced a reduction in cAMP and Ca2+ induced striatal protein phosphorylation. Facilitatory actions of the ganglioside GM1 dominate following a lesion, probably due to its possible function as a modulator of receptors for neuronotrophic factors, leading to restoration of metabolic rate and of cAMP and Ca2+ induced protein phosphorylation in the striatum of the lesioned side. The results emphasize that ganglioside GM1 treatment can restore the metabolism of a partially innervated striatum towards normal, as evaluated both at the level of the entire striatal structure by means of the DG and IAP techniques and at the molecular level by means of studies on the cAMP and Ca2+ induced protein phosphorylation.

Animals↗
PubMed1985

Somatostatin induced apnoea: prevention by central and peripheral administration of the opiate receptor blocking agent naloxone.

Somatostatin (SRIF) (6 nmol) given intracisternally (i.c.) into the alpha-chloralose anaesthetized rat has recently been shown to cause apnoea with a latency of 5-10 minutes (Kalia et al. 1984a). The apnoea produced by SRIF is very rapid, irreversible and leads to the death of the animal. In view of the existence of SRIF nerve cell bodies and terminals in medullary respiratory nuclei such as the ventral and ventrolateral subnuclei of the nucleus of the tractus solitarius (nTS) (Kalia et al. 1984b, Johanson et al. 1984), we have proposed the existence of somatostatinergic mechanisms in the respiratory nuclei of the medulla oblongata involved in mediating apnoeic conditions (Kalia et al. 1984a). In the present study, we have analysed whether the SRIF induced apnoea could be counteracted by a previous i.c. administration of the highly selective alpha 2-adreno-receptor blocking agent RX 781094 (2-(2-(I,4 benzodioxanyl]2-imi-dazoline HCl) (Doxey et al. 1983), or an opiate receptor blocking agent such as naloxone. Thus, both alpha 2-adrenoreceptor agonists and opiates induce respiratory depression, and opiates in high doses cause apnoea (Bolme et al. 1974, Hassen et al. 1982, Sitsen et al. 1982). In addition, catecholamine (CA) and enkephalin immuno-reactive nerve terminal networks exist in high densities within the nucleus tractus solitarius (nTS) of the medulla oblongata and may therefore interact with somatostatin nerve terminals in regulation of respiratory activity (Kalia et al. 1984b).

Animals↗
PubMed1985

Acute continuous exposure to cigarette smoke produces discrete changes in cholecystokinin and substance P levels in the hypothalamus and preoptic area of the male rat.

By means of a Walton Horizontal Smoking Machine, male rats were exposed to the smoke from I-4 cigarettes burned in a continuous fashion. Cholecystokinin (CCK) and substance P levels (determined by means of radio-immunoassay) were measured in discrete hypothalamic and preoptic regions. Acute continuous exposure to cigarette smoke induced increases in CCK levels in the paraventricular hypothalamic region as well as decreases in CCK levels in the median eminence. Furthermore, this treatment resulted in decreased CCK and substance P levels in the medial preoptic region. The results have been interpreted to indicate that CCK and substance P containing neuronal systems can be regulated by cholinergic nicotine-like receptors.

Animals↗
PubMed1985

Cholecystokinin neuron systems and their interactions with the presynaptic features of the dopamine neuron systems. A morphometric and neurochemical analysis involving studies on the action of cholecystokinin-8 and cholecystokinin-58.

A unique role for CCK-58 compared to that for CCK-8 has been demonstrated in the modulation of central catecholaminergic mechanisms and neuroendocrine functions. It is of paramount importance to localize CCK-58 immunoreactivity within the brain in order to establish if separate CCK-58- and CCK-8-immunoreactive neuron systems exist. The two most significant actions of CCK-58 are a marked lowering of TSH secretion and a selective increase of DA turnover in DA-CCK co-existing synapses in the nucleus accumbens and tuberculum olfactorium.

Animals↗
PubMed1985

Evidence for cholecystokinin-dopamine receptor interactions in the central nervous system of the adult and old rat. Studies on their functional meaning.

Evidence has been presented for the existence of interactions between CCK and DA receptors both in striatal and limbic membranes. A similar type of modulation by CCK-8 of DA receptors also exists after chronic neuroleptic treatment indicating that supersensitive DA receptors are also modulated by this peptide. As seen from simulation curves, CCK-8 increases the binding of [3H]DA agonists and reduces the binding of [3H]DA antagonists in striatal membranes, suggesting that CCK-8 may increase striatal DA transmission. Results of this type may underlie some of the non-neuroleptic effects of CCK-8. In the aged brain, the ability of CCK-8 to modulate DA antagonist binding sites is changed such that the binding of [3H]DA antagonists is increased. Thus, in the aged brain, receptor-receptor interactions may be altered, leading to a derangement of heterostatic mechanisms (mechanisms changing chemical transmission without interfering with synaptic homeostasis). It was also demonstrated that during aging there is a preferential disappearance of CCK-like immunoreactivity versus TH immunoreactivity in the nigral DA neurons, especially in the medially located nigral DA cells; furthermore, co-existence in the TH/CCK co-storing terminals in the nucleus accumbens was reduced during aging. Such alterations should also lead to changes in heterostatic regulation because the CCK co-modulation line controlling the DA receptors may be preferentially affected.

Aging↗