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PubMed1989

Mu opiate receptors are selectively labelled by [3H]carfentanil in human and rat brain.

[11C]Carfentanil is a potent opioid agonist currently in use as a specific PET (position emission tomography) scan radioligand for brain mu opioid receptors. In order to investigate the receptor interactions of carfentanil in detail [3H]carfentanil was used as a radioligand for labelling receptors in rat and human brain tissue homogenates. [3H]Carfentanil was found to bind saturably and with high affinity (KD = 0.08 +/- 0.01 nM) to membranes prepared from human cortical (Bmax = 42 +/- 3 fmol/mg) and thalamic (Bmax = 84 +/- 3 fmol/mg) tissues and rat cortex (Bmax = 82 +/- 4 fmol/mg) and diencephalon (Bmax = 105 +/- 5 fmol/mg). Association (1.23 +/- 0.19 X 10(10) Mol-1 X min-1 and dissociation rate (0.19 +/- 0.03 min-1) constants were determined in human cortical tissues; results from studies in rat cortical, and rat diencephalon tissue homogenates produced similar kinetic rate constants. Competition studies with a variety of drugs indicated that [3H]carfentanil interacts primarily with mu opioid receptors in the four tissues studied; the affinities of a series of non-radioactive opioid ligands were essentially identical in the four tissues (correlation coefficients = 0.88-0.93). Naloxone, morphine, DAGO [( D-Ala2-MePhe4-Gly-ol5]enkephalin), DADL [( D-Ala2-D-Leu5]enkephalin) and EKC (ehtylketazocine) potently displaced specific [3H]carfentanil binding with nM potency while the kappa agonist U-69593, the sigma agonists (+)-SKF 10047, (+)-3-PPP [3-hydroxyphenyl)-N-propylpiperidine) and haloperidol and PCP (phencyclidine) were less potent displacing agents. The higher affinities of DAGO and morphine versus DADL for the [3H]carfentanil binding sites indicates that delta opioid receptors are not being labelled.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Effects of castration and androgen treatment on aromatase activity in the brain of mature male Atlantic salmon (Salmo salar L.) parr.

Brain homogenates from male Atlantic salmon parr aromatized tritiated androstenedione to estrogens. The aromatase activity in homogenates of whole brains from castrated male parr was lower than that in homogenates from sham-operated male parr in autumn. This was also found in homogenates of the telencephalon and diencephalon, but not in homogenates of the tectum opticum. Treatment of castrated males with testosterone (T) and 11-ketoandrostenedione (OA) increased the aromatase activity in whole brains. T, but not OA, also significantly increased aromatase activity in all brain parts. In spring, half a year after the peak breeding period, mature parr males had a lower aromatase activity in telencephalon, diencephalon and tectum than that found in castrated males in autumn, whereas immature males displayed an even lower level of activity.

Androgens↗
PubMed1994

Food deprivation increases brain nitric oxide synthase and depresses brain serotonin levels in rats.

We studied nitric oxide (NO) synthase activity and serotonin content in the diencephalon of 24 hr food deprived rats. NO synthase activity was significantly increased whereas serotonin levels together with those of tryptophan and 5-hydroxyindoleacetic acid (5-HIAA) were reduced in food deprived rats when compared to control rats. NG-Nitro-L-arginine (L-NO Arg), an inhibitor of NO synthase, was used as a tool to study the role of NO in food deprivation. Twenty-four hr food deprived male Sprague-Dawley rats were intraperitoneally (i.p.) administered L-NO Arg (12.5, 25 and 50 mg/kg) before food presentation. Control rats received a NaCl (0.9%) solution. Food consumption was monitored 1 and 2 hr after food presentation. L-NO Arg administration produced a dose-dependent reduction in food intake. Pretreatment with metergoline (2 mg/kg) but not with ritanserin (1 mg/kg) antagonized the anorectic effect of L-NO Arg. Moreover, in the diencephalon L-NO Arg significantly reduced NO synthase activity whereas it increased serotonin levels. Our data indicate that NO might have a physiological role in the regulation of food intake and suggest that brain NO may modulate the central serotoninergic system.

Amino Acid Oxidoreductases↗
PubMed1983

The development and restriction of the ipsilateral retinofugal projection in the chick.

Although it is generally believed that the central projections of the retina in birds are entirely crossed, using wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) as an anterograde tracer, we have found that in normal posthatched chicks there is a small ipsilateral retinofugal projection to the diencephalon and midbrain. Most of the ipsilateral fibers appear to be directed to the lateral anterior and dorsolateral anterior nuclei of the thalamus, to the pretectal region, and to the ectomammillary nucleus and the adjoining nucleus externus. Even in the best preparations the numbers of ipsilateral fibers are so small that it is hardly surprising that they have been overlooked in previous axonal degeneration and autoradiographic experiments. A significantly larger ipsilateral retinal projection develops during the second week of incubation. The ipsilaterally directed fibers can be first seen on the fifth day of incubation and their numbers appear to increase until about embryonic day 12. At this stage the projection involves substantially more fibers than at hatching and is also more extensive in its distribution; in fact, in its general organization (but not its size) it closely parallels the normal crossed retinofugal system, contributing fibers to essentially all the primary visual relay nuclei in the diencephalon and midbrain and to much of the optic tectum, where the densest projection is to its caudomedial aspect. During the second week of incubation there is also a small number of retinal fibers, which after crossing in the optic chiasm, recross the midline in the posterior and tectal commissures (and also in the tectal roof plate), before ending in the pretectal region of the ipsilateral side. In addition, there is a markedly aberrant projection from the retina into the contralateral optic nerve. Most of the ipsilateral retinal fibers are eliminated between the twelfth and sixteenth days of incubation, and by day 17 the ipsilateral projection is reduced to its mature form. The progressive reduction in the ipsilateral projection occurs at a time when it is known (from other studies) that there is an appreciable loss of retinal ganglion cells; but whether the reduction is due to neuronal death or to the selective elimination of ipsilateral axon collaterals remains to be determined. The existence of a significant ipsilateral retinofugal component early in development, probably accounts, in part, for the distinctive and persistent ipsilateral projection that occurs if one eye is removed during the first few days of incubation.

Animals↗
PubMed1983

Diencephalic sites from which calling can be evoked with small currents in Japanese quail.

A systematic stimulation survey f the diencephalon in Japanese quail, showed that calling could be evoked with currents as low as in the midbrain (less than 50 microA). These low threshold areas were located in the pre-optic area and posterior hypothalamus. Both are likely to influence output, but are not on a calling motor pathway from the forebrain. Putative pathways for calling had somewhat higher thresholds, than the preoptic area and posterior hypothalamus. Calling was evoked from much of the diencephalon with currents up to 200 microA, but positive sites tended to be located posteriorly. A few of the calls elicited resembled natural calls subjectively, but statistical analyses showed significant differences. Most elicited calls were unlike any spontaneous call and could be produced in both sexes.

Animals↗
PubMed1994

Post-stimulation excitability of diencephalic self-stimulation neurons.

We used the double-pulse technique with moveable electrodes to estimate the refractory periods of self-stimulation neurons within the rat's dorsal diencephalon and surrounding areas. Refractory period estimates varied substantially depending on the site of stimulation. For some sites, recovery from refractoriness was noted at post-stimulation intervals as short as 0.5 ms, an estimate similar to that reported for the MFB axis and the dorsal raphe and periaqueductal grey. The longest recovery intervals were similar to those reported for the prefrontal cortex, caudate, and substantia nigra. Step-like recovery (believed to indicate the presence of neural populations with non overlapping refractory periods) was also noted in several sites. The large range of recovery intervals found in the present study may suggest that the diencephalon plays an integrative role for rewarding signals arriving from various brain areas.

Animals↗
PubMed1994

Cell type- and region-specific expression of aromatase mRNA in cultured brain cells.

The expression of aromatase mRNA in cultured mouse brain cells was measured by a quantitative reverse transcription-PCR method using an internal standard. Aromatase mRNA was expressed in the cultured neurons prepared from diencephalon at 0.037 +/- 0.005 attomol/microgram total RNA. However, the mRNA was detected in neither the neurons from cerebral cortex nor astrocytes. These results demonstrate that expression of aromatase mRNA is regulated in cell type- and region-specific manners in cultured brain cells. The aromatase mRNA levels in neurons obtained from diencephalon were not affected by administration of testosterone, estradiol, dexamethasone, forskolin, or 12-O-tetradecanoyl 13-acetate. The results are in apparent disagreement with previous reports concerning regulation by androgens of brain aromatase activity in vivo and may suggest that aromatase expression in brain neurons is not directly induced by androgens. Androgen induction of brain aromatase may be mediated by several steps including cell-cell (neuron-neuron and/or neuron-glia) interaction.

Animals↗
PubMed1984

Somatostatin in the brain of the turtle Testudo hermanni Gmelin. An immunohistochemical mapping study.

An immunohistochemical mapping study in the brain and upper spinal cord of the turtle Testudo hermanni Gmelin revealed a wide distribution of somatostatin perikarya and fibres. Within the telencephalon, somatostatin perikarya are present in the anterior olfactory nucleus, in the medial, dorsomedial and dorsal cortex, in the pallial thickening, in the piriform cortex, paleostriatum augmentatum, in the dorsoventricular ridge, core nucleus of the dorsoventricular ridge, in area c and d, and in the amygdala. In the diencephalon, the periventricular nucleus of the hypothalamus contains many somatostatin perikarya. Cerebrospinal fluid contacting somatostatin perikarya of the infundibular nucleus terminate with club-like endings in the ventricular cavity. Some somatostatin perikarya are present in the nu. reuniens of the thalamus and in the lateral habenular nucleus of the epithalamus. Within the mesencephalon somatostatin perikarya are located in the interpeduncular nucleus, area tegmentalis ventralis and in the nu. reticularis isthmi. In the rhombencephalon, somatostatin perikarya are encountered in the nu. raphe superior, nu. reticularis magnus, periventricular grey matter, bed nucleus of the fasciculus longitudinalis medialis and in the nu. solitarius-vagus complex. Somatostatin fibres form a circular band in the olfactory bulb. In the telencephalon, dense aggregations of somatostatin fibres are present in the anterior olfactory nucleus, in the pallial thickening, in the parahippocampal gyrus, cortex medialis, dorsomedialis, dorsalis and piriformis, in the dorsal ventricular ridge, paleostriatum augmentatum, area c and d, in the septum, nu. diagonalis of Broca, in the amygdala and in the anterior commissure. In the diencephalon, somatostatin fibres terminate at the vessels of the organum vasculosum of the lamina terminalis. A dense band of somatostatin fibres surrounds the rostral third ventricle. Somatostatin fibres terminate in the infundibulum at portal capillaries, and in the neural lobe. Somatostatin fibres are found in the periventricular, ventromedial and lateral nucleus of the hypothalamus. In the thalamus, the area triangularis, the dorsomedial and dorsolateral area and the nu. reuniens contain somatostatin fibres. Somatostatin fibres are very dense in the lateral habenular nucleus. At the mesencephalic level, somatostatin fibres are found in the pretectal nucleus, in the deep layers of the tectum, in the nu. tori semicircularis lateralis, in the interpeduncular nucleus, area tegmentalis ventralis, nu. ruber, substantia nigra and periventricular grey.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1983

Octavolateral projections to the torus semicircularis of the trout, Salmo gairdneri.

Microiontophoretic delivery of horseradish peroxidase in the torus semicircularis of the trout resulted in heavy labeling of somata in the rhombencephalic nucleus intermedius octavolateralis and nucleus octavus magnocellularis. In addition some labeled somata were found closely to the fasciculus longitudinalis lateralis and in the diencephalon. Efferents leave the torus to the diencephalon, the tegmentum and the tectum and, via the fasciculus longitudinalis lateralis, to the rhombencephalon and the spinal cord. It is concluded that in the trout the torus receives octaval and lateral line input mainly directly from the octavolateral area in the hindbrain, without involvement of a superior olive.

Animals↗
PubMed1993

Neural projections of the pineal organ in the larval sea lamprey (Petromyzon marinus L.) revealed by indocarbocyanine dye tracing.

The distribution of the central neural connections of the pineal organ of the larval sea lamprey was investigated by means of anterograde and retrograde tracing with the fluorescent lipophilic dye, DiI (1,1'-dioctadecyl 3,3,3',3'-tetramethylindocarbocyanine perchlorate). Pinealofugal projections are well developed in larvae, extending from the posterior commissure into the diencephalon and mesencephalon. Small numbers of neurons were retrogradely labelled in the transition zone between the diencephalon and the mesencephalic tegmentum. These cells may constitute the first pinealopetal system described in anamniotes.

Animals↗
PubMed1983

A comparison of the distribution of central cholinergic neurons as demonstrated by acetylcholinesterase pharmacohistochemistry and choline acetyltransferase immunohistochemistry.

The topographical distribution of cholinergic cell bodies has been studied in the rat brain and spinal cord by choline acetyltransferase (ChAT)-immunohistochemistry and acetylcholinesterase (AChE)-pharmacohistochemistry using diisopropylfluorophosphate (DFP). The ChAT-containing cells and the cells that stained intensely for AChE 4-8 hr after DFP were mapped in detail on an atlas of the forebrain (telencephalon, diencephalon) hindbrain (mesencephalon, rhombencephalon) and cervical cord (C2, C6). Striking similarities were observed between ChAT-positive cells and neuronal soma that stained intensely for AChE both in terms of cytoarchitectural characteristics, and with respect to the distribution of the labelled cells in many areas of the central nervous system (CNS). In the forebrain these areas include the caudatoputamen, nucleus accumbens, medial septum, nucleus of the diagonal band, magnocellular preoptic nucleus and nucleus basalis magnocellularis. In contrast, a marked discrepancy was observed in the hypothalamus and ventral thalamus where there were many neurons that stained intensely for AChE, but where there was an absence of ChAT-positive cells. No cholinergic perikarya were detected in the cerebral cortex, hippocampus, amygdala and dorsal diencephalon by either histochemical procedure. In the hindbrain, all the motoneurons constituting the well-established cranial nerve nuclei (III-VII, IX-XII) contained ChAT and exhibited intense staining for AChE. Further, a close correspondence was observed in the distribution of labeled neurons obtained by the two histochemical procedures in the midbrain and pontine tegmentum, including the laterodorsal tegmental nucleus, some areas in the caudal pontine and bulbar reticular formation, and the central gray of the closed medulla oblongata. On the other hand, AChE-intense cells were found in the nucleus raphe magnus, ventral part of gigantocellular reticular nucleus, and flocculus of the cerebellum, where ChAT-positive cells were rarely observed. According to both techniques, no positive cells were seen in the cerebellar nuclei, the pontine nuclei, or the nucleus reticularis tegmenti pontis. Large ventral horn motoneurons and, occasionally, cells in the intermediomedial zone of the cervical cord displayed ChAT-immunoreactivity and intense AChE staining. On the other hand, AChE-intense cells were detected in the dorsal portion of the lateral funiculus, but immunoreactive cells were not found in any portion of the spinal cord white matter.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholine↗
PubMed1986

Influence of thyroidectomy on brain catecholamines during the postnatal period.

The influence of early thyroidectomy (Tx) on changes in dopamine (DA) and noradrenaline (NA) during the postnatal period (30, 45 and 60 days old) was studied in the diencephalon and the rest of the brain of male and female rats. Thyroidectomy interfered with the normal growth of the animals, decreased brain weight and markedly influenced the developmental pattern of both DA and NA in the diencephalon. When compared with control values, the DA concentration, in 45- and 60-day-old Tx male rats, was 29 and 43% lower, respectively, and 21 and 43% lower, respectively, in Tx females. Diencephalic NA levels in Tx rats were also lower than those observed in controls, 15% inferior in 45- and 60-day-old males; 27 and 22% lower, respectively, in females. Thyroidectomy does not significantly alter the level of either amine in the rest of the brain.

Animals↗
PubMedDate not supplied

Distribution of serotonin- and dopamine-immunoreactivity in the brain of the teleost Clarias gariepinus.

The distribution of serotonergic and dopaminergic cell bodies and varicose fibres in the brain of the teleost Clarias gariepinus was studied immunohistochemically using antisera against formaldehyde-conjugated serotonin and dopamine. Many serotonergic and dopaminergic fibres innervated the areas dorsalis telencephali pars medialis and pars lateralis dorsalis, as well as the area ventralis telencephali pars ventralis. In the diencephalon, a large number of serotonergic and some dopaminergic fibres were found in the preoptic nucleus, innervating the cells of this nucleus. In addition, serotonergic and dopaminergic fibres were observed in the pituitary stalk and in all regions of the pituitary gland. Moreover, the diencephalon contained the highest number of serotonin- or dopamine-immunoreactive cell bodies. These cells were confined to the same periventricular nuclei as the nucleus ventromedialis thalami, the nucleus posterior periventricularis, the nucleus lateralis tuberis, the nuclei recessus lateralis and recessus posterioris. Most cells of these nuclei were in contact with the cerebrospinal fluid of the third ventricle. The brainstem contained serotonergic cell bodies in the raphe nuclei and a few serotonergic and dopaminergic fibres. The torus semicircularis was densely innervated by serotonergic fibres and, to a lesser extent, dopaminergic fibres. In the midbrain of Clarias gariepinus, no dopaminergic homologue of the substantia nigra was observed. The results are discussed both in a comparative and a physiological context. In this regard, special attention has been paid to the contribution of hypothalamic monoamines in the regulation of gonadotropin secretion as an essential step in the neuro-endocrine control of reproduction.

Animals↗
PubMedDate not supplied

The serotoninergic system of the brain of the lamprey, Lampetra fluviatilis: an evolutionary perspective.

The distribution of serotonin(5HT)-immunoreactive cell bodies, nerve fibers and terminals was investigated by light microscopy in the lamprey Lampetra fluviatilis. Twenty-three distinct groups of 5HT neuronal somata were identified from diencephalic to rhombencephalic levels in the brain. The diencephalon contained a subependymal population of immunoreactive cells in contact with the cerebrospinal fluid (CSF), which could be subdivided into five separate groups situated in the hypothalamus and ventral thalamus; five additional groups of immunoreactive diencephalic neurons, situated in the dorsal thalamus and thalamo-pretectum, which were not in contact with the CSF, were also identified. In the midbrain, in addition to a few labelled neurons in the optic tectum, two structures containing immunoreactive cells were identified in the tegmentum mesencephali. None of these 5HT cells corresponded to the retinopetal neurons which are situated in the same region. A very large number of 5HT neurons were observed in the hindbrain which could be divided into seven groups in the isthmus rhombencephali and a further three in the rhombencephalon proper. Immunoreactive fibers and terminals were widely distributed throughout the neuraxis. In the telencephalon two 5HT fibers assemblies, lateral and medial, could be identified which terminated in both pallial and subpallial structures. The richest serotoninergic innervation in the telencephalon was found in the lateral portion of the primordium hippocampi and the medial part of the corpus striatum. In the diencephalon, the distribution of immunoreactive fibers and terminals was heterogeneous, being most pronounced in the lateral hypothalamic area and in the infundibulum. The densest arborization of fibers in the mesencephalon was found in the stratum fibrosum et cellulare externum of the optic tectum, a major site of retinal projection, and in the nucleus interpeduncularis mesencephali as well as in the oculomotor nuclei. The rhombencephalon is richly endowed with serotoninergic fibers and terminals, many labelled arborizations being found in the nuclei isthmi rhombencephali and around the nucleus motorius nervi trigemini. Comparative analysis of the serotoninergic systems of petromyzontiforms and gnathostomes indicates that the evolution of this system involves a progressive elimination of the rostral immunoreactive cells and an increasing complexity of the caudal population of serotoninergic neurons.

Animals↗
PubMed1992

Regional expression of the homeobox gene Nkx-2.2 in the developing mammalian forebrain.

A novel mouse homeobox-containing gene, Nkx-2.2, has been isolated. Nkx-2.2 is a member of a family of genes whose homeodomains are homologous to that of the Drosophila NK-2 gene. Nkx-2.2 transcripts are found in localized domains of the brain during mouse embryogenesis. Nkx-2.2 expression in the brain abuts and partially overlaps with the expression domains of two other related homeobox-containing genes, TTF-1 and Dlx. The expression domains of the three genes in the developing prosencephalon coincide with anatomical boundaries, particularly apparent in the diencephalon. This result raises the possibility that these genes may specify regional differentiation of the developing diencephalon into its anatomically and functionally defined subregions. Nkx-2.2 may be involved in specifying diencephalic neuromeric boundaries.

Animals↗
PubMed1994

Embryonic neurons of the developing optic chiasm express L1 and CD44, cell surface molecules with opposing effects on retinal axon growth.

The first retinal ganglion cell axons arriving at the embryonic mouse ventral diencephalon encounter an inverted V-shaped neuronal array defining the midline and posterior boundaries of the future optic chiasm. These neurons express L1, an immunoglobulin superfamily molecule known to promote retinal axon outgrowth, and CD44, a cell surface molecule that we find inhibits embryonic retinal axon growth in vitro. Incoming retinal axons do not penetrate this L1/CD44 neuron array, but turn to establish the characteristic X-shaped optic chiasm along the anterior border of this array. These results suggest that L1/CD44 neurons may serve as an anatomical template for retinal axon pathways at the embryonic mouse ventral diencephalon.

Animals↗
PubMed2005

The pattern of c-fos activation in the CNS is related to behavior in the mudskipper, Periophthalmus cantonensis.

The effects of three types of behavior on c-fos activation in different brain regions of the mudskipper, Periophthalmus cantonensis, were studied by immunocytochemistry. Animals were divided into four groups: The control group did not undergo any specific treatment. The second group consisted of animals that were agitated for an hour with a glass rod at an irregular speed. The third group contained animals showing aggressive behavior during an hour of monitoring, i.e. documented territorial hostility by raising of dorsal fins and pursuit of intruders. In contrast to these three groups, which had last been fed 24h earlier, the fourth group included animals that had been nourished 1h prior to sacrifice. Results showed that, in most brain regions of control animals, there were relatively few c-fos positive cells. After fish had been agitated, however, very prominent c-fos label was seen in the lateral and medial parts of the telencephalon, the thalamus, hypothalamus, pituitary and medulla. In aggressive fish, a significant increase in the number of c-fos positive sites, as compared to control fish, was observed in the diencephalons, pons and medulla, but not in the telencephalon. After feeding, there was a less substantial increase in c-fos protein expression in the diencephalon, but an even more prominent c-fos activation in the pons and medulla. Our present results support the hypothesis that, in fish, the medial telencephalon is involved in avoidance reaction and the lateral telencephalon in spatial memory, whereas rhombencephalic activation may reflect activity of cranial nerve nuclei.

Aggression↗
PubMed2006

Characterization of [125I]ZM 241385 binding to adenosine A2A receptors in the pineal of sheep brain.

Adenosine is a ubiquitous neuromodulator and homeostatic regulator that exerts its physiologic actions through activation of A(1), A(2A), A(2B) and A(3) adenosine receptor subtypes. In the central nervous system, adenosine's action in neurons is manifested in its modulation of tonic inhibitory control. Adenosine released in the brain during hypoxia has critical depressant effects on breathing in fetal and newborn mammals, an action suggested to be mediated by A(2A) receptors in the posteromedial thalamus. In an effort to more accurately define the spatial distribution of adenosine A(2A) receptors in fetal sheep diencephalon, we have used a receptor autoradiographic technique utilizing an iodinated radioligand [(125)I]ZM 241385, which has greater sensitivity and resolution than the tritiated compound. The distribution of ligand binding sites in the fetal sheep diencephalon indicated that the highest levels of binding were in select thalamic nuclei, including those implicated in hypoxic depression of fetal breathing, and the pineal. Given the high density of labeled A(2A) receptors in the pineal, these sites were characterized more fully in homogenate radioligand binding assays. These data indicate that [(125)I]ZM 241385 binding sites display a pharmacological signature consistent with that of adenosine A(2A) receptors and are expressed at similar levels in fetal, lamb and adult ovine brain. The adenosine A(2A) receptor pharmacologic signature of the [(125)I]ZM 241385 binding site in pineal cell membranes generalized to the site characterized in membranes derived from other portions of the lamb thalamus, including the sector involved in hypoxic inhibition of fetal breathing. These results have important implications for the functional roles of adenosine A(2A) receptors in the thalamus and pineal of sheep brain.

Adenosine↗