Search PubMed⌕ Search

Biomedical subjects

K Fuxe

Publications and source records attributed to K Fuxe.

At least 181 records · Page 10Linked to original sources
PubMed1996

Ibotenic acid in the medial septum increased brain-derived neurotrophic factor mRNA levels in the dorsal rat hippocampal formation.

Excitotoxic lesion of the medial septum with ibotenic acid leading to partial disappearance of the septal cholinergic nerve cells was used to investigate the role of cholinergic mechanisms in the control of trophic factors for hippocampal plasticity, namely brain-derived neurotrophic factor (BDNF) and glucocorticoid receptor (GR). Their mRNA levels were tested by in situ hybridization 13 days after the lesion. A persistent and widespread increase of BDNF mRNA was found in all parts of the dorsal hippocampal formation that was not accompanied by a significant modification in GR expression. The present data suggest that subcortical excitotoxic lesions at the septal level have long-term consequences for the adaptive trophic responses occurring in the dorsal hippocampus.

Animals↗
PubMed1996

The vigilance promoting drug modafinil increases dopamine release in the rat nucleus accumbens via the involvement of a local GABAergic mechanism.

The present in vivo microdialysis study demonstrated that the subcutaneous injection of modafinil (diphenyl-methyl-sulfinyl-2-acetamide) in doses of 30-300 mg/kg dose dependently increased dopamine release from the intermediate level of the nucleus accumbens along the rostro-caudal axis of the halothane anaesthetized rat. The effect of modafinil in a dose of 100 mg/kg was counteracted by the local perfusion in the nucleus accumbens with the GABAB receptor antagonist phaclofen (beta-p-chlorophenyl-gamma-aminopropyl-phosphonic acid) (50 microM), the GABAA agonist muscimol (3-hydroxy-5-aminomethyl-isoxazolol) (10 microM) and the neuronal GABA reuptake inhibitor SKF89976A (4,4-diphenyl-3-butenyl-nipecotic acid) (0.1 microM), whereas it was increased by the GABAB receptor agonist (-)-baclofen [beta-(p-chlorophenyl-gamma-aminobutyric acid)] (10 microM). In addition, the modafinil-induced increase of dopamine release was associated with a significant reduction of accumbens GABA release. These results suggest that the dopamine releasing action of modafinil in the rat nucleus accumbens is secondary to its ability to reduce local GABAergic transmission, which leads to a reduction of GABAA receptor signaling on the dopamine terminals.

Analysis of Variance↗
PubMed1996

Stimulation of adenosine A1 receptors prevents the EEG arousal due to dopamine D1 receptor activation in rabbits.

The influence of adenosine A1 (N6-cyclopentyladenosine, CPA) and A2 (2-[4-(2-carboxylethyl)phenethylamino]-5'-N-ethylcarboxamido -adenosine hydrochloride, CGS 21680) receptor agonists on SKF 38393-induced electroencephalographic (EEG) arousal was studied in rabbits. While CPA (0.1 mg/kg i.v.) significantly prevented the EEG effects of SKF 38393, CGS 21680 (0.2 mg/kg i.v.) did not affect them. These results demonstrate that adenosine A1 receptors can modulate dopamine D1 receptor-induced EEG arousal and show, for the first time, that adenosine-dopamine interactions are involved in brain functions other than motor activity.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1996

Adenosine A1 receptor-dopamine D1 receptor interaction in the rat limbic system: modulation of dopamine D1 receptor antagonist binding sites.

Antagonistic interactions between adenosine A2a and dopamine D2 receptors and between adenosine A1 and dopamine D1 receptors have been previously found in the basal ganglia. Those interactions have been proposed to be key mechanisms of action responsible for the motor depressant effects of adenosine agonists and the motor activating effects of adenosine antagonists, like caffeine. By using quantitative receptor autoradiography, the selective adenosine A1 receptor agonist N6-cyclopentyladenosine was found to decrease the affinity of dopamine D1 receptors for the specific D1 antagonist [(125)I]SCH 23982 in both the nucleus accumbens and the medial prefrontal cortex of the rat brain. The present results suggest that dopamine neurotransmission, through an A1-D1 interaction, might also he involved in the behavioural effects of adenosine agonists and antagonists not related to motor activity, like the sedative-hypnogenic properties of adenosine analogues and the psychostimulant effects of caffeine.

Adenosine↗
PubMed1996

The secretory trypsin inhibitor like-peptide, PEC-60 increases dopamine D2 receptor agonist induced inhibition of GABA release in the dorsolateral neostriatum of the awake freely moving rat. An in vivo microdialysis study.

The effects of local perfusion with the secretory trypsin inhibitor like-peptide, PEC-60 on dopamine and gamma-aminobutyric acid (GABA) release in the dorsolateral neostriatum and GABA release in the globus pallidus were studied using in vivo microdialysis in the awake freely moving rat. Local perfusion with PEC-60 (500 nM and 1 microM) increased dopamine release in the dorsolateral neostriatum while the highest (1 microM) concentration of PEC-60 decreased striatal but not pallidal GABA release. An inactive form of the peptide, S-carboxyamidomethylated PEC-60 (1 microM) failed to influence either striatal dopamine and GABA or pallidal GABA release. In addition, when PEC-60, at a dose which did not affect striatal and pallidal GABA release (100 nM), was co-perfused together with the dopamine D2 receptor agonist pergolide (500 nM), a potentiation in the ability of pergolide to reduce GABA release in the dorsolateral neostriatum was observed and this effect was counteracted by co-perfusion with the selective dopamine D2 receptor antagonist raclopride (1 microM). In contrast, the pergolide induced inhibition of striatal dopamine release was unaffected by PEC-60 (100 nM). These data indicate that PEC-60 differentially regulates dopamine and GABA release in the dorsolateral neostriatum by a selective and facilitory interaction with the postsynaptic dopamine D2 receptor possibly involving high-affinity PEC-60 like-peptide binding sites located on local axon collaterals of a discrete subpopulation of efferent GABA neurons and/or on GABA interneurons.

Animals↗
PubMed1996

On the role of glucocorticoid receptors in brain plasticity.

1. The mapping of glucocorticoid receptors (GR) in the rat central nervous system (CNS) has demonstrated their widespread presence in large numbers of nerve and glial cell populations also outside the classical stress regions. 2. The present paper summarizes the evidence that glucocorticoids via GR in the CNS can act as lifelong organizing signals from development to aging. The following examples are given. (a) In the prepubertal and adult offspring, prenatal corticosterone treatment can produce long-lasting changes in striatal dopaminergic communication. (b) In adulthood, the evidence suggests complex regulation by adrenocortical hormones of neurotrophic factors and their receptors in the hippocampal formation. (c) In aging, the strongly GR-immunoreactive pyramidal cell layer of the CA1 hippocampal area appears to be preferentially vulnerable to neurotoxic actions of glucocorticoids, especially in some rat strains. 3. Strong evidence suggests that each nerve cell in the CNS is supported by a trophic unit, consisting of other nerve cells and glial cells, blood vessels, and extracellular matrix molecules. Due to multiple actions on nerve and glial cell populations of the different trophic units, the glucocorticoids may exert either an overall trophic or a neurotoxic action. It seems likely that with increasing age, the endangering actions of glucocorticoids on nerve cells prevail over the neurotrophic ones, leading to reduced nerve cell survival in some trophic units.

Adrenal Cortex Hormones↗
PubMed1996

Regulation of dopamine D2 receptor affinity by cholecystokinin octapeptide in fibroblast cells cotransfected with human CCKB and D2L receptor cDNAs.

Alteration in dopamine (DA) and/or cholecystokinin (CCK) transmission in the CNS may be of relevance for schizophrenia. Previous findings in striatal membranes give indications of a modulation of DA D2 receptor affinity by CCKB receptor activation. In the present study receptor binding studies were performed in a mouse fibroblast cell line (L-hD2l/CCK), expressing both human D2 receptors (long form, D2L) and human CCKB receptors, and binding sites for [3H]CCK-8S (sulfated CCK octapeptide), the D2 agonist [3H]NPA and the D2 antagonist [3H]raclopride were found and characterized in saturation and competition experiments. 1 nM of CCK-8 caused a significant 38% increase in the KD value of the D2 agonist [3H]NPA binding sites in the L-hD2l/CCK cell membranes. This change was blocked by the CCKB receptor antagonist PD 134308 (50 nM). Furthermore, 1 nM of CCK-8 increased the KD value of the D2 antagonist [3H]raclopride binding sites by 34% (P < 0.05) in the L-hD2l/CCK cell membranes. Control cells (L-hD2l cells) expressing D2L receptors showed no specific [3H]CCK-8S binding sites and no modulation by CCK-8 of the D2L receptors. These findings indicate a modulation of the D2L receptor affinity by activation of the CCKB receptor also when they are coexpressed in a fibroblast cell line. One possible explanation of these data may include a receptor-receptor interaction between the CCKB and D2L receptors.

Animals↗
PubMed1996

Chronic continuous infusion of (-)nicotine reduces basic fibroblast growth factor messenger RNA levels in the ventral midbrain of the intact but not of the 6-hydroxydopamine-lesioned rat.

A negative correlation has been found between smoking and Parkinson's disease. There is evidence to suggest that this correlation appears to be associated with a neuroprotective role of nicotine for dopamine neurons at least in relation to mechanical injury. However, 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine (MPTP) neurotoxicity to dopamine neurons is enhanced by chronic continuous (-)nicotine. More recently, basic fibroblast growth factor has been found to possess neurotrophic activities for many nerve cells including the dopamine cells in vivo and in vitro. Therefore, it is of interest to explore a possible effect of nicotine on basic fibroblast growth factor expression in the ventral midbrain of intact and 6-hydroxydopamine-lesioned rats and how treatment with nicotine can alter the 6-hydroxydopamine-induced injury of the nigral dopamine nerve cells as evaluated by dopamine biochemistry. In the present paper, an analysis of the effects of chronic continuous infusion of (-)nicotine via minipumps was carried out on basic fibroblast growth factor expression in the vental midbrain of the intact male rat and of the 6-hydroxydopamine lesioned rat. A quantitative messenger RNA protection assay analysis was used as well as an immunocytochemical analysis in the substantia nigra. Our findings give evidence that a two-week continuous infusion with (-)nicotine in the intact rat leads to substantial and dose-related (0.03-0.3 mg/kg per h) reductions of basic fibroblast growth factor messenger RNA levels in the ventral midbrain. These changes are not associated with changes in neuronal and glial basic fibroblast growth factor immunoreactivity in this region with the antibodies used. However, a one-week continuous infusion with (-)nicotine (0.125 mg/kg per h) failed to significantly alter the basic fibroblast growth factor messenger RNA levels in the ventral midbrain of solvent and 6-hydroxydopamine-injected rats and thus also the 6-hydroxydopamine-induced increase of basic fibroblast growth factor messenger RNA levels in the ventral midbrain of the lesioned side observed at this time-interval and known to be of astroglial origin [Chadi G. et al. (1994) Neuroscience 61, 891-910]. In agreement, the 6-hydroxydopamine-induced depletion of dopamine in the neostriatum was unaltered by the nicotine treatment (0.125 mg/kg per h). Thus, chronic continuous (-)nicotine treatment may lead to a reduced basic fibroblast growth factor trophic tone in the ventral midbrain of the intact but not of the 6-hydroxydopamine-lesioned rat neither on the lesioned nor on the unlesioned side of the ventral midbrain. It seems possible that chronic nicotine treatment mainly reduces basic fibroblast growth factor messenger RNA levels of neuronal origin, since the astroglial messenger RNA levels dominate after the 6-hydroxydopamine-induced lesions.

Animals↗
PubMed1996

Functional neuroanatomy of the nigrostriatal and striatonigral pathways as studied with dual probe microdialysis in the awake rat--II. Evidence for striatal N-methyl-D-aspartate receptor regulation of striatonigral GABAergic transmission and motor function.

In the present study we used the dual probe approach to investigate striatal N-methyl-D-aspartate receptor regulation of GABA release from the substantia nigra pars reticulata of the awake, freely moving rat. One microdialysis probe of concentric design was implanted in the dorsolateral striatum and another in the ipsilateral substantia nigra pars reticulata. Perfusion with N-methyl-D-aspartate (100 microM) in the dorsolateral striatum decreased local dopamine release (-25%) and increased both glutamate (+40%) and GABA (+35%) release. Moreover, perfusion with N-methyl-D-aspartate (100 microM) in the dorsolateral striatum increased GABA release (+20%) in the substantia nigra pars reticulata. Perfusion with the lower (10 microM) N-methyl-D-aspartate concentration in the dorsolateral striatum did not affect striatal dopamine, glutamate and GABA release or nigral GABA release. Intrastriatal perfusion with the N-methyl-D-aspartate receptor antagonist dizocilpine maleate (10 microM), at a dose which by itself did not affect basal striatal or nigral neurotransmitter levels, prevented the effects of striatal perfusion with N-methyl-D-aspartate on both striatal and nigral neurotransmitter release. Intrastriatal dizocilpine maleate was also perfused concurrently with intranigral tetrodotoxin (10 microM) (see accompanying paper). Intrastriatal perfusion with dizocilpine maleate prevented the tetrodotoxin-induced rise in both striatal and nigral GABA levels and profoundly reduced the tetrodotoxin-induced contralateral turning. In addition, intrastriatal dizocilpine maleate delayed the increase in striatal glutamate release evoked by intranigral tetrodotoxin without affecting the associated decrease in striatal dopamine release. The present study demonstrates that N-methyl-D-aspartate receptors in the dorsolateral striatum regulate GABA release in the substantia nigra pars reticulata of the awake rat and provides evidence that this regulation plays a key role in motor function.

Animals↗
PubMed1996

Functional neuroanatomy of the nigrostriatal and striatonigral pathways as studied with dual probe microdialysis in the awake rat--I. Effects of perfusion with tetrodotoxin and low-calcium medium.

In the present study we employed the dual probe approach to investigate functional interactions between the nigrostriatal dopaminergic and striatonigral GABAergic pathways in the awake, freely moving rat and their role in motor function. One microdialysis probe of concentric design was implanted in the substantia nigra pars reticulata and another in the ipsilateral dorsolateral striatum. Perfusion with a low-Ca2+ (0.1 mM) medium and with the voltage-dependent Na(+)-channel blocker tetrodotoxin (10 microM) was alternatively performed in both brain regions and the dialysate dopamine, glutamate and GABA levels were simultaneously measured in the dorsolateral striatum, whereas GABA levels alone were monitored in the substantia nigra. Perfusion with a low-Ca2+ medium in the substantia nigra pars reticulata did not affect local GABA levels, but transiently increased striatal dopamine release (+40%) without modifying striatal glutamate and GABA levels. Conversely, intranigral perfusion with tetrodotoxin transiently increased local GABA levels (+40%), while it decreased striatal dopamine (-60%) and increased glutamate (+70%) and GABA (+50%) levels. Perfusion with a low-Ca2+ medium in the dorsolateral striatum reversibly decreased local dopamine (-70%), glutamate (-20%) and GABA (-20%) levels, while local perfusion with tetrodotoxin decreased dopamine (-70%), increased glutamate (+30%) but did not affect dialysate GABA levels in this brain area. Neither of these intrastriatal treatments significantly affected GABA levels in the substantia nigra. Intranigral but not intrastriatal perfusion with tetrodotoxin was also associated with an increase in spontaneous locomotor activity as expressed by contralateral turning. Intranigral and intrastriatal perfusion with low-Ca2+ medium did not influence locomotor activity. On the basis of these neurochemical and behavioural findings, we propose a new dynamic model for the study of motor behaviour as mediated by basal ganglia circuitry.

Animals↗
PubMed1996

Localization of neuropeptide Y Y1 receptor-like immunoreactivity in catecholaminergic neurons of the rat medulla oblongata.

Neuropeptide Y receptors in the medulla oblongata participate in central cardiovascular control. The neuropeptide Y1 receptor subtype gene and amino acid sequence have been identified by molecular cloning studies. In this study, a C-terminal peptide representing amino acids 355-382 of the neuropeptide Y1 receptor was synthesized and cross-linked to thyroglobulin to produce an antibody against a partial sequence of the neuropeptide Y1 receptor, used to localize neuropeptide Y1 receptor-like immunoreactivity in the catecholaminergic neurons of the medulla oblongata. The double colour immunofluorescence technique with a polyclonal antibody against the neuropeptide Y1 receptor and a monoclonal antibody against tyrosine hydroxylase revealed that in the rat medulla oblongata, a weak (the C3 cell group) to moderately intense (the A1, A2, C1 and C2 cell groups), diffuse cytoplasmic neuropeptide Y1 receptor-like immunoreactivity was distributed primarily in the noradrenergic and adrenergic cell bodies and occasionally seen in the noradrenergic and adrenergic cell processes. Almost all tyrosine hydroxylase-like immunoreactive cell bodies in the A1, A2, C1, C2 and C3 cell groups showed neuropeptide Y1 receptor-like immunoreactivity. The neuropeptide Y1 receptor-like immunoreactivity in the A2 cell group was somewhat stronger. The present findings show localization of specific neuropeptide Y1 receptor-like immunoreactivity in the vast majority of the noradrenergic and adrenergic cell bodies of the A1, A2, C1, C2 and C3 cell groups, which are putative cardiovascular regions. The results support the view that neuropeptide Y1 receptors in the medulla oblongata are involved in central cardiovascular control and may coexist with another important receptor, the alpha 2A-adrenoceptor, also involved in central, cardiovascular regulation, since the alpha 2A-adrenoceptor-like immunoreactivity has been shown to exist in almost all noradrenergic and adrenergic cell bodies in the brainstem. In conclusion, centrally administered neuropeptide Y may act in part via neuropeptide Y1 receptors located on the soma and dendrites of noradrenergic and adrenergic neurons, where it may interact with alpha 2-adrenoceptors at least in the noradrenergic A2 neurons. This noradrenaline system may be involved in at least part of the vasodepressor actions of neuropeptide Y, noradrenaline and adrenaline in the nucleus tractus solitarii in view of the present findings.

Animals↗
PubMed1996

Evidence for a differential cholecystokinin-B and -A receptor regulation of GABA release in the rat nucleus accumbens mediated via dopaminergic and cholinergic mechanisms.

In the present study we characterized the cholecystokinin receptor regulation of (i) the dopamine D2 agonist binding sites in striatal sections including the nucleus accumbens and (ii) GABA and dopamine release in the central part of the rat nucleus accumbens, by combining the in vitro filter wipe-off and the in vivo microdialysis techniques. In the binding study we demonstrate that sulphated cholecystokinin octapeptide (1 nM) increased (219 +/- 30%) the KD value of the D2 agonist [3H]N-propylnorapomorphine binding sites in sections from the striatum including the accumbens. This effect was counteracted by the cholecystokinin-B antagonist PD134308 (50 nM). In a parallel study using microdialysis in the central nucleus accumbens, we found that local perfusion with sulphated cholecystokinin octapeptide (1 microM) induced an increase in GABA (135 +/- 7%) and dopamine (146 +/- 8%) release which was unaffected by the cholecystokinin-A antagonist L-364,718 (10 nM). In contrast, when the cholecystokinin-B antagonist PD134308 (10 nM) was co-perfused with the peptide it prevented the increase in dopamine and decreased GABA release (-24 +/- 2%). This reduction was counteracted by the addition to the perfusate medium of the cholecystokinin-A antagonist or the cholinergic muscarinic M2 receptor antagonist AF-DX 116 (0.1 microM). Taken together, these data demonstrate that the facilitation by sulphated cholecystokinin octapeptide of GABA and dopamine release in the central accumbens probably reflects an inhibitory effect of the peptide on both pre- and postsynaptic D2 receptors, mediated via cholecystokinin-B receptor activation. In addition, for the first time we provide evidence for a differential cholecystokinin-A and -B receptor-mediated regulation of GABA transmission in the central accumbens, where the cholecystokinin-B receptor exerts a dominant excitatory influence while the cholecystokinin-A receptor mediates an inhibition of GABA release via a local muscarinic M2 receptor.

Animals↗
PubMed1996

Computer-assisted mapping of basic fibroblast growth factor immunoreactive nerve cell populations in the rat brain.

We have performed a mapping of basic fibroblast growth factor (bFGF) immunoreactive (ir) glial and nerve cell populations in the male rat brain using a rabbit antibody raised against a synthetic peptide of bovine bFGF. Regional morphometric and microdensitometric analysis of the bFGF ir neuronal profiles in coronal brain sections was carried out by means of an automatic image analyser. The density and intensity of the bFGF ir glial profiles were subjectively evaluated. The bFGF immunoreactivity (IR) was detected within the cytoplasm of neurons, except within the pyramidal neurons of hippocampal CA2 region, the fasciola cinerea and the indusium griseum, where bFGF IR was present in the nucleus. In contrast, in glial cells bFGF IR was always found in the nucleus. Neuronal and glial IR was no longer observed after absorption of the bFGF antiserum with recombinant bFGF. Basic FGF IR was found in neuronal and glial cell populations throughout the brain as well as in the choroid plexus and in the ependymal cells lining the ventricles. Basic FGF ir nerve cells were found in all layers of both the neocortex and allocortex. Within the caudate putamen and the nucleus accumbens a low density of weak bFGF ir neuronal profiles was detected. The majority of the thalamic nuclei showed medium to high densities of moderate to strong bFGF ir neuronal profiles. All the hypothalamic nuclei, with the exception of the anterior and lateral hypothalamic area and of the ventral hypothalamic nucleus, contained a high density of bFGF ir profiles. The pons and the medulla oblongata were characterized by the presence of a large number of nuclei containing moderate to high densities of strong bFGF ir profiles. The Purkinje cell layer of the cerebellar cortex contained a high density of moderately bFGF ir profiles. A moderate density of strong bFGF ir nerve cell profiles was observed within all the laminae of the spinal cord, except within the II and III laminae where a high density of strongly ir profiles was found. Histogram analysis of total immunoreactivity showed that the distribution of bFGF ir profiles within the telencephalon and mesencephalon tend to be similar with regard to the central tendency and spread. Using Kendall's tau, a significant correlation between intensity and density values was obtained only in the diencephalon. The cytoplasmic bFGF IR found in distinct nerve cell populations all over the rat brain and spinal cord may represent forms of bFGF which can be released from the nerve cells via non-exocytotic mechanisms in view of the absence of an intracellular signal peptide in bFGF. The presence of nuclear bFGF IR within the glial cells all over the central nervous system (CNS) suggests an intracellular function of bFGF, such as the promotion of mitogenesis and/or participation in the transcriptional regulation of various genes.

Animals↗
PubMed1996

Dopaminergic transmission in the rat retina: evidence for volume transmission.

The study was designed to determine whether dopaminergic neurotransmission in the retina can operate via volume transmission. In double immunolabelling experiments, a mismatch as well as a match was demonstrated in the rat retina between tyrosine hydroxylase (TH) and dopamine (DA) immunoreactive (ir) terminals and cell bodies and dopamine D2 receptor-like ir cell bodies and processes. The match regions were located in the inner nuclear and plexiform layers (D2 ir cell bodies plus processes). The mismatch regions were located in the ganglion cell layer, the outer plexiform layer, and the outer segment of the photoreceptor layer, where very few TH ir terminals can be found in relation to the D2 like ir processes. In similar experiments analyzing D1 receptor like ir processes versus TH ir nerve terminals, mainly a mismatch in their distribution could be demonstrated, with the D1 like ir processes present in the outer plexiform layer and the outer segment where a mismatch in D2 like receptors also exists. The demonstration of a mismatch between the localization of the TH terminal plexus and the dopamine D2 and D1 receptor subtypes in the outer plexiform layer, the outer segment and the ganglion cell layer (only D2 immunoreactivity (IR)) suggests that dopamine, mainly from the inner plexiform layer, may reach the D2 and D1 mismatch receptors via diffusion in the extracellular space. After injecting dopamine into the corpus vitreum, dopamine diffuses through the retina, and strong catecholamine (CA) fluorescence appears in the entire inner plexiform layer and the entire outer plexiform layer, representing the match and mismatch DA receptor areas, respectively. The DA is probably bound to D1 and D2 receptors in both plexiform layers, since the DA receptor antagonist chlorpromazine fully blocks the appearance of the DA fluorescence, while only a partial blockade is found after haloperidol treatment which mainly blocks D2 receptors. These results indicate that the amacrine and/or interplexiform DA cells, with sparse branches in the outer plexiform layer, can operate via volume transmission in the rat retina to influence the outer plexiform layer and the outer segment, as well as other layers of the rat retina such as the ganglion cell layer.

Animals↗
PubMed1996

Dopamine D1 receptor-mediated facilitation of GABAergic neurotransmission in the rat strioentopenduncular pathway and its modulation by adenosine A1 receptor-mediated mechanisms.

By using in vivo microdialysis it was found that one of the main functions of striatal dopamine D1 receptors is to selectively facilitate GABAergic neurotransmission in the 'direct' strioentopeduncular pathway. D1 receptors localized in the entopeduncular nucleus were also found to facilitate GABA release. However, results obtained from in vivo microdialysis, in vivo electrochemistry, immunohistochemistry and confocal laser microscopy suggested that entopeduncular D1 receptors could only be activated under pharmacological conditions. Adenosine A1 receptors were found to antagonistically modulate the D1-mediated regulation of the strioentopeduncular pathway. Furthermore, using in situ hybridization D1 and A1 receptors were shown to be colocalized in medium-sized striatal neurons. These results show that the strioentopeduncular neuron is a main locus for adenosine-dopamine interactions in the brain.

Animals↗
PubMed1996

The receptor mosaic hypothesis of the engram: possible relevance of Boolean network modeling.

In the past 15 years, several lines of evidence have shown that receptors for chemical signals can interact in domains of the plasma membrane and possibly form molecular circuits encoding logical operators. In this frame, the receptor mosaic hypothesis of the engram was advanced. According to this proposal, aggregates of different receptor species (mosaics) may form in neuronal membranes (typically synapses) and constitute a memory trace (engram) of its activity. In the present paper, we present an attempt to model the functioning of aggregates of interacting receptors in membrane domains by means of random Boolean networks.

Animals↗
PubMed1996

Subcellular localization of angiotensin II immunoreactivity in the rat cerebellar cortex.

We localized angiotensin II (Ang II) immunoreactivity in the rat cerebellar cortex with immunogold staining methods. Perfusion fixation with high amounts of glutaraldehyde and the use of cryoultramicrotomy caused remarkable changes in immunostaining versus formaldehyde/picric acid fixation. With the use of monoclonal and polyclonal anti-Ang II, Ang II immunoreactivity was prominent in cerebellar neurons such as Purkinje, granule, basket, and stellate cells. At the subcellular level, the peptide was clearly localized in nuclei, and in some cell types, such as endothelial and granule cells, it was nearly exclusively present in the transcriptionally active euchromatin. Intracellular Ang II immunoreactivity was also detected in vesicle-like structures in cytoplasm and mitochondria and at cell-cell contacts. Additional experiments with liver and adrenal tissue confirmed the nuclear localization of Ang II immunoreactivity, suggesting a role of Ang II in the regulation of gene transcription.

Adrenal Glands↗