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K Fuxe

Publications and source records attributed to K Fuxe.

At least 505 records · Page 28Linked to original sources

Effects of chronic exposure to cigarette smoke on amine levels and turnover in various hypothalamic catecholamine nerve terminal systems and on the secretion of pituitary hormones in the male rat.

Male rats were exposed to the smoke from 2 cigarettes every morning for a total-period of 9 days. The next day they were decapitated immediately after the exposure to the smoke from 4 cigarettes (Kentucky reference IR-1 type) burned at 30-min intervals. Control animals were exposed to air alone or to nicotine-free cigarette smoke (Cambridge glass fibre filters). In contrast to chronic exposure to filtered smoke, exposure to unfiltered smoke resulted in a 10% increase in catecholamine (CA) levels (quantitative histofluorimetry) within the lateral palisade zone, the posterior periventricular hypothalamic nucleus and within the dorsomedial hypothalamic nucleus. There was also an increase in amine turnover (tyrosine hydroxylase inhibition by alpha-methyl-dl-p-tyrosine methylester; alpha MT) in the dopamine (DA) systems of the medial and lateral palisade zones and in the periventricular noradrenaline (NA) hypothalamic systems. Chronic exposure to unfiltered cigarette smoke resulted in reductions of prolactin, LH and FSH levels (radioimmunoassay). Following alpha MT treatment chronic exposure to unfiltered cigarette smoke still led to reduced prolactin serum levels. In addition an increased vasopressin serum concentration was found. The effects of chronic exposure to cigarette smoke on neuroendocrine function and on hypothalamic CA systems are suggested to be mediated via nicotine. Combined with the results from a previous study the present results indicate that tolerance does not develop with regard to the inhibitory effects of exposure to cigarette smoke on prolactin, LH and FSH secretions. The same is true for the stimulatory effects on the tubero-infundibular DA neurons and the periventricular NA systems. But chronic exposure to cigarette smoke seemed to induce tolerance with regard to its stimulatory effects on subependymal, dorsomedial and paraventricular hypothalamic NA systems and on corticosterone release.

Adrenocorticotropic Hormone↗

Mapping of glucocorticoid receptor immunoreactive neurons in the rat tel- and diencephalon using a monoclonal antibody against rat liver glucocorticoid receptor.

By means of a monoclonal antibody against the rat liver glucocorticoid receptor (GR) in combination with the indirect immunoperoxidase technique it has been possible to demonstrate GR-immunoreactive nerve and glial cell nuclei all over the tel- and diencephalon of the male rat. Strongly GR-immunoreactive nerve cell nuclei were only present in the parvocellular part of the paraventricular hypothalamic nucleus, in the anterior periventricular hypothalamic nucleus, in the ventral part of the mediobasal hypothalamus, and in the CA1 and CA2 subregion of the hippocampal formation. Within the paraventricular hypothalamic nucleus a substantial overlap exists between the GR-immunoreactive area and the CRF-immunoreactive area. Medium to high densities of moderately GR-immunoreactive nerve cell nuclei were present all over the cortical hemispheres. Medium densities of moderately GR-immunoreactive nerve cells were demonstrated in many thalamic nuclei and in the central amygdaloid nucleus. After adrenalectomy the GR immunoreactivity was predominantly located in the pericaryon. Upon acute corticosterone treatment of adrenalectomized male rats, the GR immunoreactivity was again mainly demonstrated in the nerve cell nuclei indicating that corticosterone can translocate GR from the cytoplasm to the cell nuclei. It is suggested that the hypothalamic GR may be involved in the regulation of especially CRF secretion but also in the secretion of other anterior pituitary hormones such as TRH and somatostatin.

Adrenalectomy↗

The ergolene derivative MPME induces in the rat a behavioural syndrome associated with activation of dopamine D-1 receptors belonging to the dotted type of forebrain dopamine nerve terminals.

The ergolene derivative MPME (PTR 17402; (5R,8R)-8-(4-p-methoxyphenyl)-1-piperazynylmethyl-6- methylergolene], a dopamine (DA) receptor agonist acting mainly at DA D-1 receptors linked to dotted types of forebrain DA nerve terminals, induces a characteristic behavioural syndrome consisting of increased locomotion, head-bobbing and sniffing activity without oral stereotypies or increased rearing. Haloperidol and cis-flupenthixol, nonselective DA receptor antagonists, but not selective D-2 receptor antagonists such as remoxipride and sulpiride, could significantly counteract the locomotion and head-bobbing behaviour induced by MPME. In contrast, the sniffing behaviour induced by MPME was only marginally affected by haloperidol and cis-flupenthixol pretreatment. These results suggest that activation of D-1 receptors in the forebrain mainly linked to the dotted types of DA nerve terminals in the striatum, and in the limbic forebrain, can result in behavioural effects which differ from those caused by stimulation of D-2 receptors located mainly within the diffuse types of DA nerve terminal systems.

Animals↗

Distribution of neurophysin II immunoreactive nerve fibers within the subnuclei of the nucleus of the tractus solitarius of the rat.

The location of neurophysin II immunoreactive nerve fibers and preterminal processes has been examined in various functionally distinct subnuclei of the nucleus of the tractus solitarius (nTS) using the indirect immunofluorescence method for immunocytochemistry combined with cytoarchitectonic identification. The nTS is responsible for integrating respiratory and autonomic reflex activity: the vlnTS, vnTS, ni and nI are associated with respiratory activity; the dlnTS and dnTS are important sites for the integration of baroreceptor and chemoreceptor activity; the ncom, dnTS and dlnTS integrate cardiac afferent activity and the mnTS mediates both cardiovascular and gastrointestinal effects. At levels caudal to the obex, the ncom contained the largest number of neurophysin II immunoreactive nerve fibers and the mnTS and dmnX contained moderate neurophysin II immunoreactivity. At levels rostral to the obex the region of the dorsal medulla adjacent to the mnTS and dnTS (PVR and dPSR) showed the densest immunoreactivity and the mnTS, dmnX and vPSR showed moderate immunoreactivity. At the rostral pole of the nTS, neurophysin II immunoreactive nerve terminals were seen in the dendritic regions of cells in dmnX and mnTS. This selective distribution of neurophysin II immunoreactive nerve terminals in the cardiovascular and gastrointestinal subnuclei of the nTS implicates a direct, descending, hypothalamic, oxytocin-neurophysin II containing pathway interacting with these nTS functions. These results confirm the hypothesis (Sawchenko and Swanson) that descending neurophysin II immunoreactive pathways represent an important neuronal system for the hypothalamic regulation of cardiovascular (vasomotor) and gastrointestinal nuclei in the brainstem.

Animals↗

Somatostatin-induced apnea: interaction with hypoxia and hypercapnea in the rat.

The effects of hypoxia and hypercapnea in the production of somatostatin (SRIF)-induced apnea were studied during rebreathing experiments. Hypoxia and hypercapnea resulted in a shortening of the latency of SRIF-induced apnea. In order to exclude the effect of stimulation of central chemoreceptors by mock-CSF solution, control experiments using mock-CSF in combination with hypoxia and hypercapnea were done. No apnea could be produced by the mock-CSF in combination with hypoxia and hypercapnea. The shortening of apneic latency from 480 +/- 8 s (S.E.M.) to 148 +/- 30 s with the addition of a chemostimulus (hypoxia and hypercapnea) in SRIF-induced respiratory depression demonstrates that chemostimulation interacts with the centrally originating apnea to enhance its apneic response.

Animals↗

Evidence for the existence of putative dopamine-, adrenaline- and noradrenaline-containing vagal motor neurons in the brainstem of the rat.

A combined technique utilizing retrograde transport of horseradish peroxidase (HRP) combined with immunocytochemistry using antibodies raised against tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH) and phenylethanolamine N-methyl transferase (PNMT) has been used to characterize monoaminergic neurons located within the region of the brainstem vagal motor nucleus. TH-immunoreactive (IR) but not DBH-IR and PNMT-IR neurons were double labelled predominantly at the caudal-most pole of the dorsal motor nucleus of the vagus (dmnX), whereas double-labelled PMNT and DBH plus TH-IR neurons extended from levels just rostral to the obex to 1-2 mm rostrally in the medial and lateral poles of the dmnX, respectively. The presence of putative dopamine (DA), noradrenaline (NA) and adrenaline (A) neurons in topographically distinct regions of the dmnX implicates, DA, NA and A in the modulation of cholinergic transmission at the level of parasympathetic ganglia in discrete parts of the thoracic and abdominal viscera.

Animals↗

l-Glutamate reduces the affinity of [3H]N-propylnorapomorphine binding sites in striatal membranes.

l-Glutamate but not methyl-D-aspartate (NMDA) or quisqualate ( Quis ) (10(-6 M) in vitro with or without preincubation increased significantly the KD value of the [3H]N-propylnorapomorphine ( [3H]NPA) binding sites by 21 and 36% respectively in striatal membranes of rat without influencing the striatal [3H]spiperone binding sites. The number of striatal [3H]NPA binding sites was not changed by l-glutamate (10(-6) and 10(-5) M) in vitro. There may thus exist interactions between striatal glutamate receptors -- not related to excitatory amino-acid receptors of the NMDA or the QUIS type -- and high affinity striatal DA receptors.

Animals↗

Luteinizing hormone-releasing hormone increases dopamine turnover in the lateral palisade zone of the median eminence and reduces noradrenaline turnover in the nuc. preopticus medialis of the hypophysectomized male rat.

By means of catecholamine fluorescence histochemistry in combination with quantitative microfluorimetry the effects of luteinizing hormone-releasing hormone (LH-RH) has been studied on the amine levels and turnover in discrete catecholamine (CA) nerve terminal populations in the hypothalamus of the hypophysectomized male rat. LH-RH highly selectively increases dopamine (DA) turnover in the lateral palisade zone of the median eminence and highly selectively reduces noradrenaline turnover in the nucleus preopticus medialis without influencing amine levels in these CA nerve terminal systems. It is suggested that the ultrashort feed-back action of LH-RH involves increased release of DA in the lateral palisade zone leading to activation of the DA receptor inhibiting LH-RH release as well as a reduced noradrenaline release in the nucleus preopticus medialis leading to a reduced excitatory influence on the LH-RH neurons at the soma-dendritic level.

Animals↗

Somatostatin produces apnea and is localized in medullary respiratory nuclei: a possible role in apneic syndromes.

Immunocytochemical studies on the nucleus of the tractus solitarius and adjacent areas of the dorsal medulla of the rat demonstrate the existence of somatostatin immunoreactive nerve cell bodies and nerve terminals within the ventrolateral and ventral subnuclei of the nucleus of the tractus solitarius. Injections of somatostatin (6 nmol in 10 microliters) into the cisterna magna of chloralose-anesthetized rats produced an apnea with a latency of 5-7 min. This apnea was preceded by slow deep breathing, a reduction in heart rate and fall of arterial blood pressure. The apnea was usually irreversible leading to death of the animal. These respiratory and cardiovascular effects of somatostatin were not abolished either by bilateral vagotomy or by low decerebration (below the inferior colliculus). It is suggested that activation of somatostatin receptors linked to neurons in medullary respiratory nuclei might be responsible for the inhibition of respiratory neuronal activity and thus may mediate apneic conditions.

Afferent Pathways↗

Distribution of neuropeptide immunoreactive nerve terminals within the subnuclei of the nucleus of the tractus solitarius of the rat.

The location of substance P, enkephalin and somatostatin (SRIF), and neurophysin II immunoreactive nerve terminals and preterminal processes in the caudal part of the nucleus of the tractus solitarius (nTS) was examined by the indirect immunofluorescence method for immunocytochemistry combined with cytoarchitectural identification of nuclear subgroups in the same tissue. In 22 Sprague-Dawley rats we examined 14-micrometers-thick serial sections of the dorsal medulla at levels from 1 mm caudal to 2 mm rostral to the obex. These sections were incubated with substance P, enkephalin, somatostatin, and neurophysin II antisera. All four peptides were examined in each case and five typical levels (two caudal and three rostral to the obex) were selected for comparison of terminal distribution between peptides. All sections were photographed under the fluorescence microscope and then counter-stained with cresyl violet. This method of analysis revealed distinct patterns of neuropeptide immunoreactivity in the subnuclei of the nTS that varied according to the level of the section. The nTS is responsible for integrating respiratory, cardiovascular (baroreceptor and cardiac), and gastrointestinal functions. The ventrolateral subnucleus (Vl)nTS, ventral subnucleus (v)nTS, interstitial subnucleus (ni)nTS, and intermediate subnucleus (nI)nTS are the major respiratory subnuclei with vlnTS and vnTS prominently associated with pulmonary afferents, ni associated with laryngeal afferents, and nI with tracheal afferents. The vlnTS, vnTS, and ni showed a moderate density of somatostatin-positive nerve terminals, scattered substance P and enkephalin immunoreactivity, and no neurophysin II-positive terminals. The nI showed moderate density of substance P immunoreactive nerve terminals. The subnuclei of the nTS receiving baroreceptor and chemoreceptor afferents--dorsolateral and dorsal (dl and d) subnuclei of nTS--showed scattered substance P immunoreactive nerve terminals. The commissural nucleus of nTS (ncom), which receives most of the cardiac afferents, showed a moderate density of enkephalin-positive immunoreactive nerve terminals. The medial subnucleus (m)nTS at levels rostral to the obex, the primary site for the termination of gastrointestinal afferents, showed substance P immunoreactivity in moderate amounts and weak immunoreactivity for all the other neuropeptides. An important result of these experiments was the observation that regions of the medulla adjacent to the nTS, i.e., the ventral parasolitarius region (vPSR), dorsal (d)PSR, and the periventricular region (PVR) showed the densest amounts of immunoreactive nerve terminals.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗

Effects of gangliosides on the functional recovery of damaged brain.

The effect of GM1 ganglioside on the recovery of dopaminergic nigro-striatal neurons was studied in rats after unilateral hemitransection. GM1 treatment favoured the collateral sprouting of dopaminergic axons in the striatum as indicated by the induced increase of tyrosine hydroxylase (TH) activity and immunofluorescence. Concomitantly GM1 partially prevented the decrease of TH activity caused by the hemitransection in the substantia nigra ipsilateral to the lesion. A significant increase of TH immunoreactivity was also detected in the substantia nigra: GM1 prevented the disappearance of TH-positive cell bodies and increased the formation of TH-positive collaterals and dendrites with respect to the saline treatment. The addition of GM1 to embryonic dissociated mesencephalic cell cultures stimulates the expression of dopaminergic characteristics as suggested by the increase of 3H-DA uptake.

Animals↗

New concepts on the structure of the neuronal networks: the miniaturization and hierarchical organization of the central nervous system. (Hypothesis).

The hypothesis is introduced that miniaturization of neuronal circuits in the central nervous system and the hierarchical organization of the various levels, where information handling can take place, may be the key to understand the enormous capability of the human brain to store engrams as well as its astonishing capacity to reconstruct and organize engrams and thus to perform highly sophisticated integrations. The concept is also proposed that in order to understand the relationship between the structural and functional plasticity of the central nervous system it is necessary to postulate the existence of memory storage at the network level, at the local circuit level, at the synaptic level, at the membrane level, and finally at the molecular level. Thus, memory organization is similar to the hierarchical organization of the various levels, where information handling takes place in the nervous system. In addition, each higher level plays a role in the reconstruction and organization of the engrams stored at lower levels. Thus, the trace of the functionally stored memory (i.e. its reconstruction and organization at various levels of storage) will depend not only on the chemicophysical changes in the membranes of the local circuits but also on the organization of the local circuits themselves and their associated neuronal networks.

Aging↗

A method for rostrocaudal integration of morphometric information from transmitter-identified cell groups. A morphometrical identification and description of 5-HT cell groups in the medulla oblongata of the rat.

A method has been developed to integrate rostrocaudal information from morphometrically characterized 5-HT nerve cell groups visualized by means of the indirect immunofluorescence technique in single coronal sections of the neuroaxis. The present method has been applied to the 5-HT positive cells of the medulla oblongata of the rat. 5-HT cell body and cell group parameters were measured by the use of a semiautomatic image analyzer (Kontron, MOP AMO 2) plugged into an Apple II computer. The density distribution of 5-HT positive cells was also studied by dividing the area analyzed into unitary squares (about 120 X 120 micron) and then by considering the number of 5-HT cells falling in each of these squares. The existence of a 5-HT cell group was determined by testing the randomness of the 5-HT profiles per unitary square. The entire population of 5-HT positive cells as well as the 5-HT cell groups were described in terms of gravity center coordinates, mean maximal diameter and homogeneity index. A rostrocaudal representation of the gravity centers and of the dispersion of the 5-HT nerve cell groups around them provided an exact three-dimensional description of the respective locations of the 5-HT cell groups within the medulla oblongata. These methods can be applied to all types of transmitter-identified cell groups and at any level of the neuroaxis.

Animals↗

Central catecholamine neurons and exposure to dichloromethane. Selective changes in amine levels and turnover in tel- and diencephalic DA and NA nerve terminal systems and in the secretion of anterior pituitary hormones in the male rat.

Subacute exposure of male rats to various concentrations (70-1000 ppm) of dichloromethane (DCM) produces a selective reduction of dopamine (DA) levels without a change of DA turnover in certain types of forebrain DA nerve terminal systems. In the low concentration (70 ppm) a selective reduction of DA turnover was observed in the medial palisade zone (MPZ) of the median eminence. This chlorinated organic solvent also produced a discrete dose-dependent increase of noradrenaline (NA) turnover within the anterior periventricular hypothalamic area and with the highest concentration an increase of NA turnover in the anteromedial frontal cortex. DCM reduced NA levels dose-dependently in the posterior periventricular hypothalamic area and also reduced NA levels in the dorsomedial hypothalamic nucleus (1000 ppm). Following tyrosine hydroxylase inhibition DCM produced an inversely dose-related increase of serum LH levels and at the highest concentration an increase of ACTH secretion was observed. It is suggested that DCM can produce discrete changes in amine storage and turnover in catecholamine (CA) nerve terminal systems of the tel- and diencephalon, some of which may contribute to the DCM induced disturbances of the secretion of anterior pituitary hormones but actions on other transmitter-identified neurons involved in neuroendocrine regulation must also be considered.

Animals↗

Studies on the mechanism of action of substituted benzamide drugs.

The effects of classical neuroleptic drugs (haloperidol, chlorpromazine) and atypical neuroleptics, i.e. substituted benzamides (L-sulpiride, tiapride, FLA 731(-] on specific in vivo binding of the dopamine antagonist 3H-spiperone and the dopamine agonist 3H-n-propylnorapomorphine (3H-NPA) was examined in male rats. The atypical neuroleptics were found to be considerably more potent in displacing nigral than striatal 3H-spiperone binding while the classical neuroleptics were about equipotent in the two brain regions. The benzamides also produced considerably less displacement of 3H-spiperone in the striatum than did classical neuroleptics. Furthermore, while the classical neuroleptic drugs block the striatal 3H-spiperone and 3H-NPA binding sites to about the same degree, the substituted benzamides appear to have a higher affinity for the DA receptors labelled by 3H-NPA than those labelled by 3H-spiperone. The behavioural effects of the benzamides were found to differ from classical neuroleptic drugs particularly with regard to induction of catalepsy. Thus, the induction of cataleptic behaviour was found to correlate with displacement of 3H-spiperone in the striatum while blockade of apomorphine induced hyperactivity correlated with the displacement of spiperone in extrastriatal areas.

Animals↗

Differential effects of mecamylamine on the nicotine induced changes in amine levels and turnover in hypothalamic dopamine and noradrenaline nerve terminal systems and in the secretion of adenohypophyseal hormones in the castrated female rat. Evidence for involvement of cholinergic nicotine-like receptors.

The effects of mecamylamine on the nicotine induced changes in hypothalamic catecholamine (CA) levels and turnover in female rats ovariectomized for one month have been evaluated using a quantitative microfluorimetric approach to measure CA levels in sections of brains treated according to the Falck-Hillarp procedure for the cellular demonstration of CA. In the same group of animals the serum prolactin, LH, FSH, TSH, GH and corticosterone levels were measured using radioimmunoassay procedures. The nicotine treatment induced a significant depletion of amine stores and an increase of amine turnover in dopamine (DA) and noradrenaline (NA) nerve terminals of the median eminence and of the peri- and paraventricular and dorsomedial NA systems of the hypothalamus using the tyrosine hydroxylase (TH) inhibition model. Mecamylamine (2 X 1 mg/kg) partly counteracted the nicotine induced reduction of amine stores in peri- (anterior part) and paraventricular NA nerve terminal systems as well as the nicotine induced increase of NA turnover in these systems, but not the action of nicotine on the CA systems of the median eminence. Nicotine (4 X 2 mg/kg) significantly and markedly reduced prolactin, LH, TSH, and GH secretion increased corticosterone secretin but did not influence FSH secretion. These effects were partly counteracted by mecamylamine (2 X 1 mg/kg) in the case of prolactin, LH and TSH secretion but not in the case of GH and corticosterone secretion. Taken together the results show that mecamylamine treatment (2 X 1 mg/kg) differentially counteract nicotine induced changes of amine levels and turnover in peri- (anterior part) and paraventricular NA nerve terminal systems indicating that the cholinergic nicotine-like receptors located in peri- (anterior part) and paraventricular areas may be more susceptible to the blocking activity of mecamylamine than those located in the median eminence area. Furthermore, the inhibitory effects of nicotine on prolactin, LH and TSH secretion are differentially counteracted by mecamylamine. In conclusion, other inhibitory systems than the tuberoinfundibular DA neurons in the MPZ and LPZ must also be involved in mediating the inhibitory effects of nicotine on prolactin, LH and TSH secretion and different types of cholinergic nicotine-like receptors may exist.

Animals↗