Biomedical subjects

H W Steinbusch

Publications and source records attributed to H W Steinbusch.

At least 19 recordsLinked to original sources

PubMed2001

The three dimensional structure of the islands of Calleja: a single heterogenous cell complex.

The islands of Calleja in the rat brain stain brilliantly and stand out clearly using the NADPH-diaphorase histochemical staining. The 3-D structure of the Islands of Calleja was mapped in sagittal sections of young adult (3 months) and aged (28 months) animals. Contours were determined using a camera lucida method, and transferred to a computer equipped with an image analyzing system. Alignment of the sections using fixed anatomical anchers revealed that the islands of Calleja were one continuous structure at both ages studied. The structures varied between animals, and there was a pronounced left-right difference in the individual rats.

Animals↗

PubMed2001

The effects of phosphodiesterase inhibition on cyclic GMP and cyclic AMP accumulation in the hippocampus of the rat.

The effects of selective and non-selective 3',5'-cyclic nucleotide phosphodiesterase (PDE) inhibitors on cGMP and cAMP accumulation were studied in rat hippocampal slices incubated in vitro. The following PDE inhibitors were used: vinpocetine and calmidazolium (PDE1 selective), erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA, PDE2 selective), SK&F 95654 (PDE3 selective), rolipram (PDE4 selective), SK&F 96231 (PDE5 selective), the mixed type inhibitors zaprinast and dipyridamole, and the non-selective inhibitors 3-isobutyl-1-metylxanthine (IBMX) and caffeine. cGMP levels were increased in the presence of different concentrations of IBMX, EHNA, dipyridamole, vinpocetine and rolipram. cGMP immunocytochemistry showed that incubation with different inhibitors in the presence and/or absence of sodium nitroprusside resulted in pronounced differences in the extent and regional localization of the cGMP response and indicate that PDE activity in the hippocampus is high and diverse in nature. The results suggest an interaction between cGMP and cAMP signalling pathways in astrocytes of the rat hippocampus.

1-Methyl-3-isobutylxanthine↗

PubMed2001

Nitric-oxide-induced cGMP synthesis in cholinergic neurons in the rat brain.

Nitric oxide (NO)-mediated cGMP synthesis is localized throughout the rat brain in close proximity to the NO-synthase-containing structures. However, characterization of the cGMP synthesizing structures in terms of co-localization with the classical neurotransmitter systems has not yet been reported. Here we present evidence, using double immunostaining for cGMP and the vesicular acetylcholine transporter, that virtually all of the cholinergic fibers in the cerebral cortex and the majority of the cholinergic fibers in the basal ganglia accumulate cGMP in response to a NO donor. In these areas, only few cGMP-containing fibers were observed not to be part of the cholinergic system. Co-localization between cGMP and the vesicular acetylcholine transporter was only observed to a minor degree in the ventral forebrain, the hippocampus, the reticular thalamic nucleus, and the nucleus ambiguus. No association of cGMP synthesis with the cholinergic system was observed to a similar extent in other brain areas. These results, in combination with literature data on the distribution of cholinergic receptors in the rat brain, suggest that NO has an anterograde and/or retrograde signaling function on subsets of cholinergic neurons.

Acetylcholine↗

PubMed2001

Behavioural correlates of striatal glial fibrillary acidic protein in the 3-nitropropionic acid rat model: disturbed walking pattern and spatial orientation.

The 3-nitropropionic acid animal model is a model where excitotoxicity, mitochondrial dysfunction and oxidative stress, mechanisms common to various neurodegenerative diseases, are involved. The present study investigated whether behavioural alterations in this model were related to striatal damage. Wistar and Lewis rats were exposed to 3-nitropropionic acid and their behavioural performance (open field, walking pattern and Morris Water Maze task) was tested after the injections and after a recovery period of 3 weeks. No changes in activity were found in the open field test. Altered walking pattern was observed in the footprint analysis, although a different response was observed in the Wistar rats compared to the Lewis rats. Initially increased latency times were observed during visual discrimination learning in the Morris Water Maze task in 3-nitropropionic acid-treated Wistar rats compared to Wistar controls. During spatial discrimination learning (invisible platform) in the Morris Water Maze task the swimming velocity was decreased in both rat strains as a result of 3-nitropropionic acid treatment. Increased striatal glial fibrillary acidic protein concentration in Wistar rats correlated with several parameters of the footprint analysis and with the latency and distance in visual as well as spatial discrimination learning in the Morris Water Maze. It is concluded that measurement of walking pattern and spatial orientation performance are sensitive indicators to monitor behavioural changes in relation to striatal degeneration in the 3-nitropropionic acid animal model. In addition, Lewis rats are less sensitive towards 3-nitropropionic acid treatment than Wistar rats.

Animals↗

PubMed2001

Distribution of DARPP-32 immunoreactive structures in the quail brain: anatomical relationship with dopamine and aromatase.

We recently demonstrated that dopamine (DA) as well as different DA receptor agonists and antagonists are able to decrease within a few minutes the aromatase activity (AA) measured in vitro in homogenates or in explants of the quail preoptic area - hypothalamus. In addition, DA also appears to regulate AA, in vivo presumably by modifying enzyme synthesis. The cellular mechanisms and the anatomical substrate that mediate these controls of AA by DA are poorly understood. Tyrosine hydroxylase-immunoreactive (TH-ir) fibers and punctate structures have been previously observed in close vicinity of aromatase-immunoreactive (ARO-ir) cells in the quail medial preoptic nucleus (POM) and bed nucleus striae terminalis (BST) but these fibers could reflect a noradrenergic innervation. We also do not know whether aromatase cells are dopaminoceptive. The main goal of the present study was therefore to bring more information on the anatomical relationships between aromatase expressing neurons and the dopaminergic system in the quail brain. The visualization by immunocytochemistry of DA and of the D1 receptor associated protein DARPP-32 was used to address these questions. DA-ir fibers were observed in the quail forebrain and overlapped extensively with nuclei that contain high densities of ARO-ir cells such as the POM and BST. This confirms that the previously reported TH-ir innervation of ARO-ir cells is, at least in part, of dopaminergic nature. DARPP-32-immunoreactive cells were found in periventricular position throughout the hypothalamus. DARPP-32-ir cells were also observed in telencephalic and mesencephalic areas (hyperstriatum accessorium, paleostriatum, nucleus intercollicularis, optic tectum). DARPP-32-ir fibers were widespread in tel-, di-, and mes-encephalic areas. The highest densities of immunoreactive fibers were detected in the lobus parolfactorius, paleostriatum augmentatum and substantia nigra/area ventralis of Tsai. In double-labeled sections, appositions between DARPP-32 fibers and ARO-ir cells were present in the dorsolateral POM and BST but DARPP-32 immunoreactivity was not detected in the ARO-ir perikarya (no colocalization). These data confirm the presence of a dopaminoceptive structures within the main cell clusters of ARO-ir cells in the quail brain but provide no evidence that these ARO-ir cells are themselves dopaminoceptive. Because DARPP-32 is not present in all types of cells expressing DA receptors, the presence of DA receptors that would not be associated with DARPP-32 in ARO-ir cells still remains to be investigated

Animals↗

PubMed2001

Relationships of 5-hydroxytryptamine immunoreactive terminal-like varicosities to 5-hydroxytryptamine-2A receptor-immunoreactive neuronal processes in the rat forebrain.

The distributions of 5-hydroxytryptamine (5-HT)-immunoreactive (IR) varicosities and 5-hydroxytryptamine-2A receptor (5-HT2A)-IR neuronal structures in the rat brain have previously been described individually. Using double labeling immunocytochemistry, the relationships between 5-HT2A-IR and 5-HT-IR elements in the forebrain of male rats has been studied at the light microscopic level. In neocortical regions (frontal, parietal and retrosplenial cortex), the strongest 5-HT2A-IR was found in the apical dendrites of pyramidal cells in layers III-V, while 5-HT-IR terminal-like varicosities were present in all layers but most prominently in the outer layers. In other forebrain regions, the olfactory bulb, the hippocampal formation, and the islands of Calleja and Calleja magna, localized discrepancies were present between the 5-HT2A-IR neuronal profiles and the 5-HT-IR terminal-like varicosities. Hardly any additional juxtapositions between the 5-HT2A-IR neuronal profiles and 5-HT-IR terminal-like varicosities were revealed when the intraneuronal level of 5-HT was increased by monoamine oxidase inhibitor pretreatment (nialamide, 250 mg/kg, 3 h). Thus, in most forebrain regions, there were overall few juxtapositions between 5-HT terminal-like varicosities and 5-HT2A-IR neuronal structures. This observation suggests that 5-HT2A receptor mediated 5-HT transmission in the rat forebrain is mainly a volume transmission process mediated via short distance diffusion in the extra-cellular space.

Animals↗

PubMed2001

Concentrations of different sterols in the striatum and serum of 3-nitropropionic acid-treated Wistar and Lewis rats.

In the present study, we examined the long-term effect of oxidative stress induced neurodegeneration on sterol concentrations in striatum and serum of Wistar and Lewis rats. Three weeks after treatment with 3-nitropropionic acid, no differences in 24S-hydroxycholesterol concentrations were observed in striatal homogenates and serum. Ratios of striatal campesterol to cholesterol were higher after 3-nitropropionic acid treatment as compared to controls of both rat strains suggesting an increased passage of this exogenous plant sterol across the blood-brain-barrier. Ratios of lathosterol to cholesterol in serum and striatum were lower in treated rats as compared with controls of both rat strains. Absolute concentrations of serum and striatal cholesterol precursors and plant sterols differed between the controls of both rat strains. It was concluded that the changes observed in sterol concentrations in the striatum and serum indicate that cholesterol homeostasis may be affected during neurodegenerative processes associated with blood-brain-barrier damage.

Animals↗

PubMed2001

Apolipoprotein E protects against neuropathology induced by a high-fat diet and maintains the integrity of the blood-brain barrier during aging.

SUMMARY: The present study provides evidence that chronic intake of a high-fat diet induces a dramatic extravasation of immunoglobulins, indicating alterations in blood-brain barrier (BBB) functioning, in the brains of apolipoprotein E (apoE)-knockout mice, but not of C57Bl/6 control mice. Using sodium fluorescein as a marker for the permeability of the BBB, we found additional support for age-related disturbances of BBB function in apoE-knockout mice. Behavioral analysis of apoE-knockout mice compared with C57Bl/6 mice indicated that they were also less efficient in acquiring the spatial Morris water maze task. Furthermore, apoE-knockout mice are known to develop severe atherosclerosis, which is exacerbated with a high-fat diet. We therefore compared the apoE-knockout mice with the apoE3-Leiden transgenic mice, which are known to develop atherosclerosis. However, apoE3-Leiden mice that were kept on a high-fat, high-cholesterol diet and that developed atherosclerosis to an extent similar to the apoE-knockout mice, showed no signs of BBB disturbances. These results indicate for the first time that apoE plays an essential role in the maintenance of the integrity of the BBB during aging and that it protects the brain from neuropathology induced by a high-fat diet. We therefore hypothesize that the role of apoE in the maintenance of the integrity of the BBB may be the mechanism by which apoE affects the progression of neurodegeneration, as seen in Alzheimer's disease.

Aging↗

PubMed2000

Whole brain spheroid cultures as a model to study the development of nitric oxide synthase-guanylate cyclase signal transduction.

Whole brain spheroids provide a suitable model to study neurodevelopment. In the literature a role for the nitric oxide (NO)-cyclic guanosine 3',5'-monophosphate (cGMP) signalling pathway during development has frequently been suggested. In this study we investigated whether functional cGMP pathways were present in differentiated spheroids. In 3-week-old spheroids soluble guanylate cyclase was stimulated with N-methyl D-aspartic acid or sodium nitroprusside (NO donor). The results showed that the NO synthase-cGMP pathway is present in the culture system. Soluble guanylate cyclase-dependent cGMP formation was found in NO synthase containing neurons, in neurons of the GABAergic, glutamatergic and cholinergic system, and in astroglia and oligodendroglia. Activation of particulate guanylate cyclase by atrial natriuretic peptide also triggered an increase in cGMP production. Particulate guanylate cyclase was found in astroglia and in microglia as well as in glutamic acid decarboxylase and calbindin containing structures and neuronal NO synthase containing neurons. Chronic inhibition of NO synthase during culture development had no effect on soluble or particulate guanylate cyclase functioning. Similarly, inhibition of soluble guanylate cyclase during culture development did not have any effect on NO synthase and particulate guanylate cyclase functioning. It is concluded that NO synthase and both soluble and particulate guanylate cyclase are present in whole brain spheroid cultures and that their activity can be influenced by several stimuli. The spheroid culture system constitutes a suitable model to study the NO-cGMP pathway during brain development in mammals.

1-Methyl-3-isobutylxanthine↗

PubMed2000

S-nitroso-N-acetylpenicillamine and nitroprusside induce apoptosis in a neuronal cell line by the production of different reactive molecules.

CHP212 neuroblastoma cells were exposed to two different nitric oxide (NO) donors, S-nitroso-N-acetylpenicillamine and sodium nitroprusside. Apoptosis and necrosis were determined with flow cytometric analysis of annexin V binding and propodium iodide uptake. Both S-nitroso-N-acetylpenicillamine and sodium nitroprusside induced apoptosis, but with a different time dependency. Oxyhemoglobin (NO scavenger) attenuated the toxicity of S-nitroso-N-acetylpenicillamine, but had no effect on the toxicity of sodium nitroprusside. By contrast, deferoxamine (iron chelator) attenuated the toxicity of sodium nitroprusside, but had no effect on the toxicity of S-nitroso-N-acetylpenicillamine. Urate (ONOO(-) scavenger) did not influence the toxicity of either S-nitroso-N-acetylpenicillamine or sodium nitroprusside, but protected from SIN-1 (3-morpholinosydnonimine, ONOO(-) donor). It was shown that both dithiothreitol and ascorbic acid affected the toxicity of S-nitroso-N-acetylpenicillamine and sodium nitroprusside in opposite ways. In the presence of dithiothreitol, superoxide dismutase and catalase decreased the toxicity of sodium nitroprusside. In the presence of cells, but not in their absence, S-nitroso-N-acetylpenicillamine decomposed with a half-life of about 4 h as assessed by the production of nitrite and absorbance reduction at 335 nm. Sodium nitroprusside decomposed very slowly in the presence of cells as assessed by the production of ferrocyanide. It can be concluded that (1) slow and sustained release of NO from S-nitroso-N-acetylpenicillamine at the cell surface causes apoptosis in CHP212 cells, probably without the involvement of ONOO(-), (2) sodium nitroprusside causes apoptosis by the production of H(2)O(2) and/or iron, rather than NO, and probably has to be taken up by the cell for decomposition.

1-Methyl-4-phenylpyridinium↗

PubMed2000

Localization and age-related changes of nitric oxide- and ANP-mediated cyclic-GMP synthesis in rat cervical spinal cord: an immunocytochemical study.

An immunocytochemical technique was used to study the localization and developmental aspects of cyclic GMP (cGMP)-synthesizing structures in the cervical spinal cord of 2-week and 3-month-old Lewis rats in response to the nitric oxide (NO) donor sodium nitroprusside (SNP) and/or atrial natriuretic peptide (ANP). By using cell-specific markers, the cell structures involved were investigated. To visualize cGMP, a combined technique of low- and high-power magnification, using a confocal laser scanning microscope was used. NOS-mediated cGMP synthesis was observed in the cervical spinal cord in laminae I, II and III in 14-day-old rats, which activity was mainly absent at the age of 3 months. The involvement of NO in the NMDA-mediated increase in cGMP immunostaining (cGMP-IS) was demonstrated by the absence of cGMP-IS in slices incubated in the presence of NMDA together with the NOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME). This NO-mediated effect of NMDA on cGMP-IS was completely absent in the 3-month-old rats. ANP-mediated cGMP synthesis resulted in an increase in cGMP in laminae I and II, which was generally similar at both ages. Astrocytes in both white and gray matter were found to be cGMP-IS in the basal, NO- and ANP-stimulated conditions. Using confocal laser microscopy, NO-mediated cGMP synthesis was observed in large cholinergic terminals nearby motor neurons in the ventral horn. An extensive colocalization between NO-stimulated cGMP synthesis and parvalbumin-positive (GABAergic) neurons and fibers was observed in all laminae. In the ANP-stimulated condition, a colocalization with parvalbumin structures was found in laminae II and III. No NO- or ANP-mediated cGMP synthesis was found in fibers immunopositive for the presynaptic glutamate transporter, serotonin, or tyrosine hydroxylase.

Age Factors↗

PubMed2000

Nitric oxide synthase does not mediate neurotoxicity after an i.c.v. injection of streptozotocin in the rat.

In the present study we evaluated the possible role of nitric oxide (NO) in mediating neuronal damage in middle-aged rats after an i.c.v. injection of streptozotocin (STREP). An i.c.v. injection of STREP has been reported to decrease the central metabolism of glucose. This inhibition of the energy metabolism after STREP treatment might induce an excitotoxic mechanism, which may lead to the stimulation of NO synthase and, consequently to the synthesis of NO. On the other hand, STREP might induce oxidative stress directly by liberation of NO from its nitroso moiety. To investigate whether NO synthase is involved in a possible excitotoxic mechanism after STREP treatment, some of the rats treated with STREP (1.25 mg/ kg in 4 microl, bilaterally 2 microl/injection site) were also treated with the NO synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME, 20 mg/kg i.p. 10 min, 6, 24 and 96 h after STREP injection). To investigate whether NO liberated from STREP may be responsible for neurotoxic effects, one additional group of control rats received an i.c.v. injection of the NO donor sodium nitroprusside (SNP, 10 microg in 4 microl). We found that STREP affected the behavioral performances in the open field and two-way active avoidance task. In addition, immunostaining for glial fibrillary acidic protein, an indicator of reactive astroglial changes to neuronal damage, showed that this was mainly located in peri- and paraventricular regions of the third and lateral ventricles, like for instance in the septum, caudate putamen and hippocampus. L-NAME treatment had no protective effect on the behavioral impairments and neuronal damage of STREP-treated rats. This suggests that the neuronal damage of STREP may still be a result of the decrease in the central energy metabolism, but without the involvement of NO synthase. This was supported by measuring, using immunostaining, the NO-mediated cyclic GMP production by the enzyme soluble guanylyl cyclase in cortical slices, i.e. L-NAME did not prevent NO production after STREP administration in vitro. In addition, it was found that SNP liberated NO in vitro, whereas in vivo SNP administration did not lead to any behavioral and neuronal deficits at all. However, the present study cannot exclude the involvement of NO liberated from STREP in neuronal damage.

Animals↗

PubMed2000

Effects of hypothermia and gender on survival and behavior after perinatal asphyxia in rats.

Previous studies in rats have demonstrated that perinatal asphyxia (PA) produces long-term morphological alterations, particularly affecting hippocampus. neostriatum, and cerebral cortex. These changes were prevented by applying hypothermia during the asphyctic insult. Because these cerebral areas are involved in cognitive and motor functions, the aim of the present study was to determine whether periods of PA during normothermia or hypothermia produces long-term behavioral impairments in rats of both sexes. The cognitive and motor functions were studied using the spatial Morris water maze (MWM) task at 1.5 months, and the open field at 5 months, respectively. The present study revealed that female rats had a higher survival rate than males after PA in normothermic conditions (p < 0.014). and that hypothermia drastically prolonged the time of survival in both sexes (p < 0.001). There were no differences in learning and memory functions between groups or male and female rats when tested with MWM. Rats subjected to hypothermia treatment did not show differences in the MWM compared to controls. A lower locomotor activity in the open field test was only observed in male rats that suffered 15 and 20 min of PA in normothermia (p < 0.05). Hypothermia treatment prevented this hypoactivity. PA in females, even if severe, did not affect the motor activity. The data of both behavioral tests showed differences between sexes, i.e., the female rats learned the MWM task slower, and were more active in the open field. This work lends further support for the hypothesis that hypothermia can prevent mortality as well as long-term sequelae induced by PA.

Animals↗

PubMed2000

No colocalization of immunoreactivities for VIP and neuronal NOS, and a differential relation to cGMP-immunoreactivity in bovine penile smooth muscle.

The distribution of immunoreactivity (IR) for the neuropeptide vasoactive intestinal polypeptide (VIP) and neuronal nitric oxide synthase (nNOS) in the bovine retractor penis muscle (RP) and penile artery (PA) was studied by using two different methods. The distribution of these immunoreactivities was also compared with that of the immunoreactivity for cyclic guanosine monophosphate (cGMP). In both tissues the nerve fibers and terminals immunoreactive for VIP had a distribution that was completely different from that of the nerve fibers and terminals immunoreactive for nNOS. This contrasts with the previous observations in penile smooth muscle of other species. In the RP, as well as in the PA, many of the VIP-IR fibers were also immunoreactive for neurofilaments (NF), whereas the nNOS-IR fibers were consistently devoid of NF-IR. Stimulation with sodium nitroprusside, a nitric oxide donor, considerably increased cGMP-IR in the smooth muscle cells in both RP and PA, and in several nerve fibers in PA. Many of these cGMP-IR nerve fibers exhibited nNOS-IR, whereas none of them was immunoreactive for VIP. Our results suggest that the degree of coexistence of VIP-IR and nNOS-IR in the nerve fibers and terminals innervating penile smooth muscle show wide species differences. They also suggest that the mechanisms by which VIP could be involved in neurogenic penile erection may vary between species.

Animals↗

PubMed2000

Perinatal asphyxia results in changes in presynaptic bouton number in striatum and cerebral cortex-a stereological and behavioral analysis.

Deficits in cognitive function have been related to quantitative changes in synaptic population, particularly in the cerebral cortex. Here, we used an established model of perinatal asphyxia that induces morphological changes, i.e. neuron loss in the cerebral cortex and striatum, as well as behavioural deficits. We hypothesized that perinatal asphyxia may lead to a neurodegenerative process resulting in cognitive impairment and altered presynaptic bouton numbers in adult rats. We studied cognitive performance at 18 months and presynaptic bouton numbers at 22 months following perinatal asphyxia. Data of the spatial Morris water escape task did not reveal clear memory or learning deficits in aged asphyctic rats compared to aged control rats. However, a memory impairment in aged rats versus young rats was observed, which was more pronounced in asphyctic rats. We found an increase in presynaptic bouton density in the parietal cortex, whereas no changes were found in striatum and frontal cortex in asphyctic rats. An increase of striatal volume was observed in asphyctic rats, leading to an increase in presynaptic bouton numbers in this area. These findings stress the issue that volume measurements have to be taken into account when determining presynaptic bouton density. Furthermore, perinatal asphyxia led to region-specific changes in presynaptic bouton numbers and it worsened the age-related cognitive impairment. These results suggest that perinatal asphyxia induced neuronal loss, which is compensated for by an increase in presynaptic bouton numbers.

Adult↗

PubMed2000

NO-mediated cGMP synthesis in cholinergic neurons in the rat forebrain: effects of lesioning dopaminergic or serotonergic pathways on nNOS and cGMP synthesis.

Nitric oxide synthase (NOS) activity and NO-mediated cGMP synthesis were studied in the rat forebrain of control animals and animals which had received a unilateral lesioning of dopaminergic or serotonergic pathways. Lesioning of the dopaminergic innervation using 6-hydroxydopamine resulted in a 50% decrease in NOS activity in the lesioned frontal cortex and caudate putamen. Lesioning of the serotonergic innervation using 5,7-dihydroxytryptamine had no effect on NOS activity. NO-mediated cGMP accumulation in rat forebrain slices was not affected by 6-hydroxydopamine or 5,7, -dihydroxytryptamine lesioning. Using cGMP immunocytochemistry, it was demonstrated that NO-mediated cGMP synthesis was absent from dopaminergic, serotonergic, GABA-ergic and neuronal NOS-containing nerve fibres. A minor colocalization of cGMP immunoreactivity was found in parvalbumin-containing fibres in the cortex. Extensive colocalization between cGMP immunoreactivity and the acetylcholine transporter was found in all cortical areas and in the caudate putamen. There was no effect of the lesions on this colocalization. These results demonstrate NO-mediated cGMP accumulation in cholinergic fibres in the forebrain of the rat and suggest an anterograde signalling function of NO in cholinergic neuronal systems in the cortex and caudate putamen of the rat.

1-Methyl-3-isobutylxanthine↗

PubMed1999

Short and long term plasticity after lesioning of the cell body or terminal field area of the dopaminergic mesocorticolimbic system in the rat.

To investigate within one study regenerative capacities of dopaminergic axons and cell bodies, short and long term recovery of behavioral and biochemical impairments following a bilateral 6-hydroxydopamine (6-OHDA) lesion of the ventral tegmental area (VTA)-nucleus accumbens (NAc) pathway was investigated in rats. Novelty-induced motility, presynaptic functions and the levels of dopamine (DA) and its metabolites were reduced when cell bodies in the VTA or axons in the NAc were lesioned. Spontaneous recovery of the behavioral deficit was observed 4 weeks after a lesion of the NAc. Subsequently presynaptic functions recovered as shown by the reappearance of low dose apomorphine (50 mg/kg)-induced hypomotility, normalization of [(3)H]dopamine uptake, reinnervation of the NAc and normalization of levels of DA and its metabolites within 24 weeks. In contrast, after a VTA lesion no recovery was observed during 48 weeks, neither from hypomotility and loss of the low dose apomorphine response nor from decreased [(3)H]dopamine uptake and levels of DA in the NAc. Short term postsynaptic supersensitivity (hypermotility upon a higher dose of apomorphine (125 mg/kg)) was present 1 and 4 weeks after the lesion but not thereafter. A near total absence of dopaminergic neurons in the VTA and axons in the NAc were found 24 weeks postlesion. Treatment with the ACTH-(4-9) analog ORG 2766 (10 mg/kg s.c., 6 days once daily) facilitated recurrence of presynaptic functions after a lesion of axons but had no short or long term effect when cell bodies were lesioned. These findings substantiate the postulate that the peptide facilitates recovery processes.

Adrenocorticotropic Hormone↗

PubMed1998

On the relationship of 5-hydroxytryptamine neurons to 5-hydroxytryptamine 2A receptor-immunoreactive neuronal processes in the brain stem of rats. A double immunolabelling analysis.

The distribution of 5-HT2A receptor immunoreactivity in the brain stem was studied by means of a commercial 5-HT2A mouse monoclonal antibody against the N-terminal portion of the receptor (amino acids 1-72). The 5-HT2A immunoreactivity demonstrated in the nerve terminal or dendritic-like structures of regions of the nucleus raphe pallidus, nucleus interfascicularis, motor nucleus of the trigeminal nerve, the ventral and dorsal tegmental nuclei and the median eminence by means of double immunofluorescence procedures were shown to be associated with 5-HT immunoreactive cell body-dendritic and/or nerve terminal structures. Besides synaptic transmission the relationships are compatible with the existence of short distance volume transmission (in the microm range) in 5-HT2A mediated 5-HT communication through terminal (5-HT)-terminal (5-HT2A) or soma/dendro (5-HT)-terminal (5-HT2A) and terminal (5-HT)-dendritic (5-HT2A) interactions in discrete brain stem nuclei.

Animals↗